SCN’s national research program supports world-class, translational, regenerative medicine research, across the research continuum, to facilitate health, social and economic benefits for Canadians.
Use the searchable database below to learn more about SCN-funded stem cell and regenerative medicine research projects and clinical trials between 2016 to 2025.
Acronyms and abbreviations:
(P) Principal Investigator (Lead) on a project
(C) Co-investigator on a project
ELSI – Ethical, Legal, and Social Implications
SCN Funded Research Database
Year
Full Name
Institution
Program
Lead Investigator Last Name
Investigator role
Funded Team Members
Funding Amount
Title
Keywords
Keywords Submitted by Researchers
Project Abstract/ Summary
Project Start Date
Project End Date
Details
2016
Sandra Cohen (P)
Hôpital Maisonneuve-Rosemont
Clinical Trial Awards
Cohen
Lead
Sandra Cohen
999,968
Making cord blood hematopoietic stem cell expansion competitive
Blood
Allogeneic hematopoietic stem cell (HSC) transplant is the best available therapy to cure blood cancers. Unfortunately, 1/3 of patients do not have a matched donor (related or unrelated). Cord blood (CB) is an attractive alternative donor source due to its unique properties, including permissive mismatches, low incidence of chronic graft-versus-host disease (cGVHD) and rapid availability. A lower risk of cGVHD is very important as it is the major determinant of long-term quality of life after transplant. However, these advantages are offset by the limited cell dose (i.e. small cords), which results in delayed- or non-engraftment (recovery of blood counts), increased infections, prolonged hospitalization and early mortality. In February 2016 we launched a CB expansion clinical trial to translate to the clinic 2 Canadian discoveries, a compound developed in G. Sauvageau and A. Marinier’s laboratory (UM171) and a bioreactor system (fed-batch) from P. Zandstra’s laboratory. Combined together these ground-breaking technologies aim to increase the HSC content of CBs and reduce the associated complications.
Our long-term objective is to design newly engineered CB grafts which will combine rapid (<12 days) engraftment with maximal anti-tumor effect (cord blood T cells) and minimal side effects (low transplant related mortality and GVHD). To achieve this, we have brought together a Canadian multidisciplinary team with state-of-the-art expertise in stem cell biology, immunology, bioengineering, cell therapy and clinical transplantation.
We seek financial support to recruit additional patients to our ongoing trial to dramatically increase the competitiveness of our strategy. We will introduce 2 modifications in our manufacturing protocol, significantly reducing cost and increasing efficacy. Consequently, we will be able to initiate a minor modification in our transplantation procedure that will minimize the risk of acute GVHD, a complication that remains too frequent. In parallel, a socio-economical study will allow us to best position our expansion strategy within Canada and internationally.
Once completed, results from this trial will be transferred to our commercial vector ExCellThera, a recently created Canadian biotech. All these improvements should make expanded CB a very desirable product for patients as well as for society and could challenge the current gold standard of matched related and unrelated donor transplants. In 3-4 years we should be in a position to initiate a multicenter enlarged phase II trial to confirm efficacy and efficiency of our product, which could be paradigm changing in the field of HSC transplantation.
01/12/2016
31/12/2017
2016
Duncan Stewart (P)
Ottawa Hospital Research Institute
Clinical Trial Awards
Stewart
Lead
Duncan Stewart
999,546
Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI)
Cardiac
Rationale: Patients with a large area of damaged heart muscle after a heart attack have a high risk for heart failure and death. Cell-based gene therapy could restore working muscle in regions that otherwise would form only scar, and lead to better heart repair and function.
Purpose: The primary objectives of the ENACT-AMI trial are to determine whether the administration of a patient’s own (autologous) Endothelial Progenitor Cells (EPCs) is safe and effective in improving cardiac function following large heart attack, and whether the use of cells that are genetically engineered by adding extra copies of a gene that is critical for blood vessel function and repair, namely endothelial Nitric Oxide Synthase (eNOS), is superior to non-modified cells. A secondary objective is to determine whether the benefit of EPC therapy depends on the timing of cell delivery (5-15 days versus 16-30 days post-STEMI).
Novel aspects: The use of the patient’s own cells avoids the immunological rejection that occurs with transplantation of cells from other individuals, but is greatly hampered by the fact that the reparative activities of stem and progenitor cells are negatively influenced by the host risk factors that lead to heart disease in the first place, namely advanced age, high cholesterol, diabetes and so forth. We have shown that adding extra copies of the eNOS gene (which protects blood vessels and promotes their growth and repair) can restore the activity of EPCs from heart patients by almost 90%. ENACT-AMI is the first clinical trial in the world to include a strategy designed to enhance the function of a patient’s own cells, and the first to use combination gene and cell therapy, for the treatment of heart disease.
Benefits to Canadians and Canada: While outcomes after heart attacks have greatly improved with the advent of modern therapies to open up the blocked coronary artery (reperfusion therapy), about 20% of patients fail to receive the expected benefits of reperfusion therapy, and face the consequences of large heart damage and subsequent heart failure. Should gene-enhanced EPCs provide an effective adjunctive treatment for these patients, this would avoid a high individual burden of chronic debilitating disease, while reducing the high costs to the health care system which in Canada totals $2.8 billion per year for heart failure (heartandstroke.ca/heartreport). If successful, ENACT investigators are well positioned to disseminate such a therapy across Canada though CellCAN, a unique network of cell manufacturing facilities across Canada.
01/12/2016
31/12/2017
2016
Harold Atkins (P)
Ottawa Hospital Research Institute
Clinical Trial Awards
Atkins
Lead
Harold Atkins
215,700
Using hematopoietic stem cell transplantation to regenerate a naïve immunie system tolerant to liver allografts
Liver Failure
Although short-term results for liver transplantation are excellent, the need for immunosuppression limits quality of life and long-term survival. Many transplant patients develop post-transplant complications including renal failure, cardiovascular disease, neoplasms, and life-threatening infections. The ability to induce a state of operational tolerance, that is, graft acceptance without the need for long-term immunosuppression, would be a major advance in the field, cutting the ongoing costs of immune suppression and reducing medical complications of organ transplantation and the associated costs to the health care system.
We propose an open-label, non-regulated, REB approved, proof-of-principle trial to determine whether immunological tolerance can be created following ablation of pre-existing allograft reactive immunity and regeneration of a naive immune system from an autologous hematopoietic stem cell transplant, in recipients of a liver allograft.
By 31-December-2017, we propose to complete the intervention on 10 patients. Safety data would be available on 9 patients and preliminary efficacy data on 7 patients. By the end of the following year, safety and 1 year efficacy data would be available on all 10 recipients. Correlative studies will examine the composition and functionality of the regenerated immune system, the nature of tolerance (or reactivity) to the liver allograft and whether a previously reported gene signature can predict tolerance to the liver graft.
Key team members include Dr. G Levy directing the liver transplant team at University Health Network and Dr. H Atkins directing the HSCT team at The Ottawa Hospital. Key partners include Novartis, which is supplying Everolimus, a regulatory T cell expanding agent, for the trial and the Birmingham Foundation, which is helping defray patient living expenses. A test for determining immunological tolerance is a potential commercial offshoot of this work.
Positive results, that is 50% or more of the patients are free from rejection without immune suppression, would provide sufficient evidence to confirm the results in a randomized Phase IIB trial and would support additional Phase IIA trials testing the ability of auHSCT to generate tolerant immune systems in other (kidney, heart…) allograft recipients. Future studies would also test the ability to regenerate self-tolerant immune systems for patients with autoimmune liver diseases – potentially preventing endstage organ damage and the need for liver transplantation.
01/12/2016
31/12/2017
2016
Lauralyn McIntyre (P)
Ottawa Hospital Research Institute
Clinical Trial Awards
McIntyre
Lead
Lauralyn McIntyre
1,000,000
Cellular Immunotherapy for Septic Shock (CISS): A Phase II Multicentre Clinical Trial
Sepsis
Septic shock is a devastating illness and the most severe form of infection seen in the intensive care unit (ICU). It is common, with severe repercussions—each year in Canada, approximately 100,000 patients will be admitted with septic shock to an ICU and 20–40% will die. Survivors suffer long-term impairment in function and reduced quality of life. Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy, at a cost of approximately 4-billion dollars annually. Mesenchymal stem cells (MSCs) represent a novel treatment. In animal models, MSCs have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death.
Over the last 5 years, our team has taken the lead to develop a research program studying MSCs in septic shock. Our team is the first in the World to have conducted and completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in critical acutely ill patients and that a randomized controlled trial is feasible. Based on this, we are now moving to a larger clinical trial at several academic hospitals across Canada. This Phase II trial will continue to evaluate safety and assess if there are strong signals for clinical benefit as well as determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective.
Our multi-disciplinary team consists of a world leader in regenerative medicine and cellular therapy, internationally recognized sepsis and stem cell basic scientists, senior methodologists, clinical trialists, a health economist, stem cell manufacturing and processing experts, and a patient representative. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a highly potent cryopreserved MSC product and to ensure its efficient distribution to all of our participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support a definitive international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and quality of life of survivors of this devastating illness.
01/12/2016
31/12/2017
2016
James Shapiro (P)
University of Alberta
Clinical Trial Awards
Shapiro
Lead
James Shapiro
499,596
Clinical trials in stem cell transplantation - solving the supply and the survival problem in Type 1 diabetes
Diabetes
Diabetes is the 7th leading cause of death in North America, the leading cause of renal failure, non-traumatic limb amputations, and new cases of blindness in adults. Mortality rates of Canadians with diabetes are almost twice those without the disease. The burden to our healthcare system is staggering, with annual diabetes costs of $1.1 billion.
Presently there is no known cure. Considering the disadvantages of current available treatments, we propose the following two clinical trials (VC-01 and Autologous CD34+ Stem Cell Therapy trials) that we anticipate will contribute to more efficient and cost-effective novel treatments to T1DM and some T2DM:
• VC-01 Trial to treat patients with longstanding T1DM
The goal of this trial is to evaluate a potentially limitless source of human embryonic stem cell derived new β -cells, as a substitute for clinical islet transplantation from cadaveric donors, in a first-in human clinical study. ViaCyte Inc. has led the field with consistent progress in the development of a clinically applicable β -cell line. Ultimately, this cell source could be used to restore β -cell mass in patients with T1DM and T2DM.
Hypothesis:
Transplantation of PEC-01 stem cell derived β-cells will mature in patients with T1DM, secrete insulin in response to glucose, and be sufficiently potent to reduce or eliminate the need for exogenous insulin. When implanted within an immunoisolating device (Encaptra®), no immunosuppression will be required.
If successful, it would be perceived as a major step forward towards a durable T1DM cure.
• Autologous CD34+ Stem Cell Therapy Trial to restore self-tolerance and drive β -cell regeneration without need for immunosuppression in patients with new-onset T1DM.
The goal of this trial is to demonstrate that subjects with new-onset T1DM undergoing autologous hematopoetic stem cell mobilization and immunologic reset will have greater preservation of endogenous insulin secretion compared to controls, and foremost that the treatment is safe, without myeloablation or need for chronic immunosuppression
Hypothesis:
T-depletional and anti-inflammatory treatment will restore self-tolerance in T1DM and mobilization of autologous CD34+ stem cells coupled with a long-acting glucagon-like Peptide-1 (GLP-1) analogue, will promote pancreatic islet regeneration and repair in the absence of myeloablation.
There has been remarkable progress in understanding the potential role of sub-populations of bone marrow derived stem cells in facilitating tissue repair. Coupled with ‘immunologic reset’ to disrupt autoimmunity, this approach offers tremendous curative potential in T1DM. A large collaboration team has been established for these two trials.
01/12/2016
31/12/2017
2016
Timothy Kieffer (P)
University of British Columbia
Clinical Trial Awards
Kieffer
Lead
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere
35,431
A stem cell therapy for insulin replacement in patients with diabetes
Diabetes
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history.
01/12/2016
31/12/2017
2016
David Thompson (C)
University of British Columbia
Clinical Trial Awards
Kieffer
Co-Investigator
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere
185,021
A stem cell therapy for insulin replacement in patients with diabetes
Diabetes
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history.
01/12/2016
31/12/2017
2016
Garth Warnock (C)
University of British Columbia
Clinical Trial Awards
Kieffer
Co-Investigator
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere
82,000
A stem cell therapy for insulin replacement in patients with diabetes
Diabetes
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history.
01/12/2016
31/12/2017
2016
Graydon Meneilly (C)
University of British Columbia
Clinical Trial Awards
Kieffer
Co-Investigator
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere
115,548
A stem cell therapy for insulin replacement in patients with diabetes
Diabetes
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history.
01/12/2016
31/12/2017
2016
Megan Levings (C)
University of British Columbia
Clinical Trial Awards
Kieffer
Co-Investigator
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere
82,000
A stem cell therapy for insulin replacement in patients with diabetes
Diabetes
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history.
01/12/2016
31/12/2017
2016
Liam Brunham (P)
University of British Columbia
Impact, Clinical Translation
Brunham
Lead
Liam Brunham, Glen Tibbits
50,000
Using human pluripotent stem-cell derived cardiomycytes to investigate the mechanisms of ibrutinib-induced atrial fibrilation
Cardiac; atrial fibrilation
Ibrutinib is a new, highly effective medication used to treat blood cancers. However, up to 10% of patients receiving this medication develop an abnormal heart rhythm, called atrial fibrillation (AF) that can cause stroke. How Ibrutinib causes AF is unknown.
Human pluripotent stem cells (hPSCs) can be used to generate human heart cells (cardiomyocytes). We have shown that hPSC-derived cardiomyocytes are an excellent model system for studying drug-induced heart injury. The overall goal of this project is to use hPSC-derived cardiomyocytes to investigate the mechanisms of ibrutinib-induced AF.
We have developed unique technologies that will allow us to study this important question. This includes the ability to make cardiomyocytes representing the different heart chambers (atrial and ventricular), and to study electrical activity in cardiomyocytes. We have partnered with the Heart & Stroke Foundation of Canada for this work.
The outcomes of this study will be a novel stem cell-based model of ibrutinib-induced AF which will provide insights into the mechanisms of this side-effect, allowing us to predict which patients may be most sensitive to ibrutinib, and identify medications to treat or prevent AF in patients who receive ibrutinib, ultimately making treatment with this important new drug safer and more effective.
01/12/2016
31/12/2017
2016
Glen Tibbits (C)
Simon Fraser University
Impact, Clinical Translation
Brunham
Co-Investigator
Liam Brunham, Glen Tibbits
50,000
Using human pluripotent stem-cell derived cardiomycytes to investigate the mechanisms of ibrutinib-induced atrial fibrilation
Cardiac; atrial fibrilation
Ibrutinib is a new, highly effective medication used to treat blood cancers. However, up to 10% of patients receiving this medication develop an abnormal heart rhythm, called atrial fibrillation (AF) that can cause stroke. How Ibrutinib causes AF is unknown.
Human pluripotent stem cells (hPSCs) can be used to generate human heart cells (cardiomyocytes). We have shown that hPSC-derived cardiomyocytes are an excellent model system for studying drug-induced heart injury. The overall goal of this project is to use hPSC-derived cardiomyocytes to investigate the mechanisms of ibrutinib-induced AF.
We have developed unique technologies that will allow us to study this important question. This includes the ability to make cardiomyocytes representing the different heart chambers (atrial and ventricular), and to study electrical activity in cardiomyocytes. We have partnered with the Heart & Stroke Foundation of Canada for this work.
The outcomes of this study will be a novel stem cell-based model of ibrutinib-induced AF which will provide insights into the mechanisms of this side-effect, allowing us to predict which patients may be most sensitive to ibrutinib, and identify medications to treat or prevent AF in patients who receive ibrutinib, ultimately making treatment with this important new drug safer and more effective.
01/12/2016
31/12/2017
2016
Jean-Philip Lumb (C)
McGill University
Impact, Clinical Translation
Crist
Co-Investigator
Jean-Philip Lumb, Colin Crist
23,400
Activation of muscle stem cells by pharmacological inhibitors of elF2a phosphorylation
Muscle
There are few treatment options available for muscle wasting associated with cancer (cachexia), which affects roughly 50% of all cancer patients in Canada and has a major impact on morbidity and mortality. Cancer cachexia will benefit from the development of stem cell based therapies that promote the activity of endogenous muscle stem cells (MuSCs) to repair and contribute to new muscle. In healthy muscle, adult muscle stem cells are normally in a resting state and activate in response to muscle injury to repair muscle. Pharmacological approaches to activate muscle stem cells, or improve their intrinsic capacity to repair muscle are needed. We have demonstrated that normally resting muscle stem cells require tightly regulated levels of protein synthesis. Using genetic tools to inactivate pathways regulating protein synthesis, we demonstrate the spontaneous activation of muscle stem cells to generate new myofibres. These findings provide the conceptual basis for the current study, which aims to use pharmacological inhibition of pathways regulating protein synthesis to activate and improve the generation of myofibres from defective muscle stem cells in cachectic muscle. Using mouse models that permit the tracking of activated muscle stem cells by their expression of a red fluorescent protein, we will test known inhibitors of pathways regulating protein synthesis for their ability to activate muscle stem cells. Inhibitors that activate muscle stem cells are also expected to improve their activity under conditions that normally prevent their efficient contribution to repair, which will be tested in a preclinical mouse model of cancer cachexia.
01/12/2016
31/12/2017
2016
Colin Crist (P)
Jewish General Hospital
Impact, Clinical Translation
Crist
Lead
Jean-Philip Lumb, Colin Crist
76,442
Activation of muscle stem cells by pharmacological inhibitors of elF2a phosphorylation
Muscle
There are few treatment options available for muscle wasting associated with cancer (cachexia), which affects roughly 50% of all cancer patients in Canada and has a major impact on morbidity and mortality. Cancer cachexia will benefit from the development of stem cell based therapies that promote the activity of endogenous muscle stem cells (MuSCs) to repair and contribute to new muscle. In healthy muscle, adult muscle stem cells are normally in a resting state and activate in response to muscle injury to repair muscle. Pharmacological approaches to activate muscle stem cells, or improve their intrinsic capacity to repair muscle are needed. We have demonstrated that normally resting muscle stem cells require tightly regulated levels of protein synthesis. Using genetic tools to inactivate pathways regulating protein synthesis, we demonstrate the spontaneous activation of muscle stem cells to generate new myofibres. These findings provide the conceptual basis for the current study, which aims to use pharmacological inhibition of pathways regulating protein synthesis to activate and improve the generation of myofibres from defective muscle stem cells in cachectic muscle. Using mouse models that permit the tracking of activated muscle stem cells by their expression of a red fluorescent protein, we will test known inhibitors of pathways regulating protein synthesis for their ability to activate muscle stem cells. Inhibitors that activate muscle stem cells are also expected to improve their activity under conditions that normally prevent their efficient contribution to repair, which will be tested in a preclinical mouse model of cancer cachexia.
01/12/2016
31/12/2017
2016
Bartha Knoppers (C)
McGill University
Impact, Clinical Translation
Germain
Co-Investigator
Bartha Knoppers, Lucie Germain
10,000
Treatment of patients with corneal limbal stem cell deficiencies using epithelial grants
Ocular
This project will complete our clinical trial and allows us to seek Health Canada approval for a new modality of treatment for corneal limbal stem cell deficiency (“LSCD”) using cell therapy. LSCD is a severe disease caused by damage/depletion of the corneal stem cells in the limbal region of the eye following trauma/disease. The epithelial tissue no longer regenerates resulting in chronic inflammation, conjunctivalization and vision loss. To treat LSCD patients, we have developed a tissue engineering technique involving massive expansion of epithelial cells in vitro to produce epithelial sheets for autologous transplantation (cultured epithelial corneal autografts – “CECA”). After thirty years of experience with skin substitutes using cultured epithelial autografts (“CEA”) on burn patients, we have successfully demonstrated the effectiveness of CECA (pre-clinical studies in animal models), and initiated a clinical trial approved by Health Canada (10 patients grafted with CECA on the 15 patients approved). This is the new treatment for which Health Canada approval will be sought. Our team of scientific researchers, clinicians and ethical/legal experts, with extra funding support from CHU de Québec Hospital Research Center, FRQS ThéCell Network, we will be the first in Canada to offer CECA treatment for unilaterally blind or vision impaired patients suffering from LSCD.
Le LOEX développe le génie tissulaire afin de reconstruire des tissus in vitro à des fins cliniques. La première application fût la culture de peau pour les grands brûlés. L’œil est recouvert par la cornée, qui nécessite les cellules souches limbiques, et dont la transparence est nécessaire à la vision. L’objectif du projet est de poursuivre l'essai clinique qui consiste à greffer une culture d’épithélium cornéen autologue (CECA) chez des patients souffrant d’une déficience unilatérale en cellules souches limbiques. Cette recherche translationnelle vise à finaliser l'essai clinique chez les premiers patients greffés avec CECA au Canada et à demander l'approbation de ce traitement à Santé Canada. Le projet consistera à prélever le tissu, à cultiver les cellules épithéliales du limbe in vitro sur un gel de fibrine qui sera greffé dans l’œil des patients. L’étude permettra d'effectuer la greffe des 5 derniers patients, de finaliser le suivi de 1 an de tous les patients, d’effectuer les analyses des résultats et de la faisabilité d’utiliser les CECA pour les indications proposées. Notre équipe multidisciplinaire permettra la translation clinique du produit du génie tissulaire: CECA. Nous serons les premiers au Canada à offrir ce traitement qui vise à améliorer la vision des patients.
01/12/2016
31/12/2017
2016
Lucie Germain (P)
Université Laval
Impact, Clinical Translation
Germain
Lead
Bartha Knoppers, Lucie Germain
90,000
Treatment of patients with corneal limbal stem cell deficiencies using epithelial grants
Ocular; limbal stem cell deficiency
This project will complete our clinical trial and allows us to seek Health Canada approval for a new modality of treatment for corneal limbal stem cell deficiency (“LSCD”) using cell therapy. LSCD is a severe disease caused by damage/depletion of the corneal stem cells in the limbal region of the eye following trauma/disease. The epithelial tissue no longer regenerates resulting in chronic inflammation, conjunctivalization and vision loss. To treat LSCD patients, we have developed a tissue engineering technique involving massive expansion of epithelial cells in vitro to produce epithelial sheets for autologous transplantation (cultured epithelial corneal autografts – “CECA”). After thirty years of experience with skin substitutes using cultured epithelial autografts (“CEA”) on burn patients, we have successfully demonstrated the effectiveness of CECA (pre-clinical studies in animal models), and initiated a clinical trial approved by Health Canada (10 patients grafted with CECA on the 15 patients approved). This is the new treatment for which Health Canada approval will be sought. Our team of scientific researchers, clinicians and ethical/legal experts, with extra funding support from CHU de Québec Hospital Research Center, FRQS ThéCell Network, we will be the first in Canada to offer CECA treatment for unilaterally blind or vision impaired patients suffering from LSCD.
Le LOEX développe le génie tissulaire afin de reconstruire des tissus in vitro à des fins cliniques. La première application fût la culture de peau pour les grands brûlés. L’œil est recouvert par la cornée, qui nécessite les cellules souches limbiques, et dont la transparence est nécessaire à la vision. L’objectif du projet est de poursuivre l'essai clinique qui consiste à greffer une culture d’épithélium cornéen autologue (CECA) chez des patients souffrant d’une déficience unilatérale en cellules souches limbiques. Cette recherche translationnelle vise à finaliser l'essai clinique chez les premiers patients greffés avec CECA au Canada et à demander l'approbation de ce traitement à Santé Canada. Le projet consistera à prélever le tissu, à cultiver les cellules épithéliales du limbe in vitro sur un gel de fibrine qui sera greffé dans l’œil des patients. L’étude permettra d'effectuer la greffe des 5 derniers patients, de finaliser le suivi de 1 an de tous les patients, d’effectuer les analyses des résultats et de la faisabilité d’utiliser les CECA pour les indications proposées. Notre équipe multidisciplinaire permettra la translation clinique du produit du génie tissulaire: CECA. Nous serons les premiers au Canada à offrir ce traitement qui vise à améliorer la vision des patients.
01/12/2016
31/12/2017
2016
James Johnson (P)
University of British Columbia
Impact, Clinical Translation
Johnson
Lead
James Johnson
100,000
Image-based screening to enhance insulin production in human embryonic stem cells
Diabetes
Diabetes is caused by the lack of insulin secreting β-cells. A major goal of regenerative
medicine is the generation of fully functional β-cells, either from stem cells, but this goal has not
yet been achieved despite optimistic press reports. The path to the clinic is clear, with the first
clinical trial of transplantation of progenitor cells into patients currently underway in the US and
Canada led by the US-based Viacyte. This company hopes that these progenitor cells will
mature into fully functional β-cells after transplantation, but it is not clear from interim reports
whether this occurs in humans. Thus, efforts to generate and transplant more mature cells are
likely to be the focus of the field over the next few years. With SCN support, our laboratory
published the first, and still only, multi-parameter kinetic high-throughput screening focused on
β-cell survival and differentiation. Hits from these robust screens were subsequently validated in
human cells and in animal models. Here, we will apply our tools to embryonic stem cells and
partner with the CDRD to expand the screening up to libraries with 250K compounds. The
identification of drugs that can increase insulin production in stem cells would be a major
breakthrough.
01/12/2016
31/12/2017
2016
Timothy Kieffer (P)
University of British Columbia
Impact, Clinical Translation
Kieffer
Lead
Timothy Kieffer
100,000
Biodistribution of differentiated stem cells following subcutaneous transplant
Diabetes
Diabetes is a disease caused by insufficient production of the hormone insulin, resulting in elevated blood sugar levels and damage to several tissues leading to debilitating complications. Our overall goal is to develop a cell-based therapy for diabetes. We believe this can be achieved by the transplant of differentiated stem cells under the skin, whereby the cells take over the automatic production of insulin and control of blood sugar levels. We have developed cell culture procedures to generate large quantities of insulin-producing cells that can reverse diabetes in rodents. With support from JDRF, we are examining the effectiveness of this approach when transplanting the cells under the skin. We now plan to extend these studies by including genetically modified stem cells that will enable us to non-invasively image the cells following transplant in order to monitor their distribution throughout the body to confirm if the cells remain at the site of transplant. In addition, we will test a novel ‘kill-switch’ to determine if we can eliminate the transplanted cells by treatment with an otherwise harmless inducing agent. Collectively, these studies may provide important knowledge and added levels of safety to justify trying this therapeutic approach in humans with diabetes.
01/12/2016
31/12/2017
2016
Megan Levings (P)
University of British Columbia
Impact, Clinical Translation
Levings
Lead
Megan Levings, Lori West
62,667
Garbage to Gold: Expansion of therapeutics regulatory T cells from discarded thymus
Blood; leukemia
For many patients with blood cancers, the only option for cure is hematopoietic stem cell transplantation (HSCT). Unfortunately, HSCT can cause a complication called graft-versus-host disease (GVHD), which happens when donor immune cells attack the patient’s healthy tissues. HSCT would be safer if we could prevent/reduce GVHD without affecting its anti-cancer action.
We are developing a novel cellular therapy with regulatory T cells (Treg) to use in combination with HSCT to prevent or treat GVHD. Early studies show promise, but using currently available protocols it is difficult and time-consuming to obtain enough Tregs with the correct properties.
We investigated the possibility of isolating Tregs from a new source: a gland called the thymus, which is discarded in children undergoing heart surgery. We found huge numbers of Tregs in the thymus and that thymic Tregs prevent GVHD in mice. In order to test thymic Tregs in a clinical trial in humans we now need to develop optimized and standard methods for large-scale expansion of thymic Tregs. We will work with STEMCELL Technologies to create new reagents and protocols to achieve this aim. This ground-work will be a key step in translating this approach to the bedside to test if delivering thymic Tregs can reduce GVHD.
01/12/2016
31/12/2017
2016
Lori West (C)
University of Alberta
Impact, Clinical Translation
Levings
Co-Investigator
Megan Levings, Lori West
37,333
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease
Blood; leukemia
For many patients with blood cancers, the only option for cure is hematopoietic stem cell transplantation (HSCT). Unfortunately, HSCT can cause a complication called graft-versus-host disease (GVHD), which happens when donor immune cells attack the patient’s healthy tissues. HSCT would be safer if we could prevent/reduce GVHD without affecting its anti-cancer action.
We are developing a novel cellular therapy with regulatory T cells (Treg) to use in combination with HSCT to prevent or treat GVHD. Early studies show promise, but using currently available protocols it is difficult and time-consuming to obtain enough Tregs with the correct properties.
We investigated the possibility of isolating Tregs from a new source: a gland called the thymus, which is discarded in children undergoing heart surgery. We found huge numbers of Tregs in the thymus and that thymic Tregs prevent GVHD in mice. In order to test thymic Tregs in a clinical trial in humans we now need to develop optimized and standard methods for large-scale expansion of thymic Tregs. We will work with STEMCELL Technologies to create new reagents and protocols to achieve this aim. This ground-work will be a key step in translating this approach to the bedside to test if delivering thymic Tregs can reduce GVHD.
01/12/2016
31/12/2017
2016
Kelly McNagny (P)
University of British Columbia
Impact, Clinical Translation
McNagny
Lead
Kelly McNagny
100,000
CAR-T cell therapy targeting tumor-specific modifications of Podocalyxin in triple negative breast cancer
Breast Cancer
Despite being more likely to receive chemotherapy, or surgery plus chemotherapy, the 5-year survival of triple-negative breast cancer (TNBC) patients remains below 65%1, and novel targeted approaches are urgently needed. Chimeric antigen receptors (CAR) combine the Fv portion of monoclonal antibodies (as a single chain Fv; scFv) and the intracellular signaling domain of immune co-stimulatory molecules and the CD3 molecule with the goal of activating T-cells in an antigen-specific manner, independent of their endogenous T cell receptor (TCR) repertoire2. CAR-T therapies targeting the surface molecule CD19 have shown exceptional promise in a limited number of clinical trials for B cell malignancies3, 4. Unfortunately, there are no obvious targets on the surface of TNBC cells that could be amenable to targeting by CAR-T cells. Previous work funded by the SCN demonstrated that the protein, Podocalyxin (Podxl) could be targeted by a naked antibody to reduce invasion and metastasis of TNBC cells in vivo, and that Podxl regulates their clonogenic potential (“stemness”) in vitro. Herein we propose to develop a novel humanized antibody (hPodo447) that recognizes a post-translational modification of Podxl found on TNBC cells (and a range of other tumors) as a targeting arm for CAR-T cell therapy.
01/12/2016
31/12/2017
2016
Paula Foster (C)
University of Western Ontario
Impact, Clinical Translation
Viswanathan
Co-Investigator
Sowmya Viswanathan, Mohit Kapoor, Paula Foster
47,000
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients
Osteoarthritis
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs.
01/12/2016
31/12/2017
2016
Mohit Kapoor (C)
University Health Network
Impact, Clinical Translation
Viswanathan
Co-Investigator
Sowmya Viswanathan, Mohit Kapoor, Paula Foster
5,000
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients
Osteoarthritis
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs.
01/12/2016
31/12/2017
2016
Sowmya Viswanathan (P)
University Health Network
Impact, Clinical Translation
Viswanathan
Lead
Sowmya Viswanathan, Mohit Kapoor, Paula Foster
48,000
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients
Osteoarthritis
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs.
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia.
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia.
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia.
01/12/2016
31/12/2017
2016
Kristin Hope (P)
McMaster University
Impact Commercialization
Hope
Lead
Kristin Hope
100,000
Methods and compositions for expansion of human hematopoietic stem and progenitor cells
Blood
01/12/2016
31/12/2017
2016
Joanne Matsubara (P)
University of British Columbia
Impact Commercialization
Matsubara
Lead
Joanne Matsubara, Marinko Sarunic
85,502
Treating advanced retinal degeneration - rebuilding multiple co-dependent retinal layers with a single injection of stem cell-derived graft
Ocular
01/12/2016
31/12/2017
2016
Marinko Sarunic (C)
Simon Fraser University
Impact Commercialization
Matsubara
Co-Investigator
Joanne Matsubara, Marinko Sarunic
14,000
Treating advanced retinal degeneration - rebuilding multiple co-dependent retinal layers with a single injection of stem cell-derived graft
Ocular
01/12/2016
31/12/2017
2016
Ian Rogers (P)
Sinai Health System
Impact Commercialization
Rogers
Lead
Ian Rogers
90,811
Improving efficacy and economics of kidney disease therapies using iPS cells
Kidney Disease
01/12/2016
31/12/2017
2016
Mark Ungrin (P)
University of Calgary
Impact Commercialization
Ungrin
Lead
Mark Ungrin
100,000
Scalable production of engineered microtissues
Manufacturing
01/12/2016
31/12/2017
2016
Stephanie Willerth (P)
University of Victoria
Impact Commercialization
Willerth
Lead
Stephanie Willerth
100,000
3D bioprinting of neural tissue from human pluripotent stem cells
Neural
01/12/2016
31/12/2017
2016
Jing Wang (C)
Ottawa Hospital Research Institute
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,554
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Paul Frankland (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,554
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
David Kaplan (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Ann Yeh (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Douglas Munoz (C)
Queen's University
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Donald Mabbott (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Freda Miller (P)
The Hospital for Sick Children
Disease Team
Miller
Lead
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Cindi Morshead (C)
University of Toronto
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural; ms
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Wolfram Tetzlaff (C)
University of British Columbia
Disease Team
Miller
Co-Investigator
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland
55,556
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy.
01/12/2016
31/12/2017
2016
Guy Sauvageau (C)
Université de Montréal
Disease Team
Marinier
Co-Investigator
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau
49,992
Development of hematopoietic stem cell expanding molecules towards the ideal transplant
Blood
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications.
01/12/2016
31/12/2017
2016
Anne Marinier (P)
Université de Montréal
Disease Team
Marinier
Lead
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau
405,557
Development of hematopoietic stem cell expanding molecules towards the ideal transplant
Blood
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications.
01/12/2016
31/12/2017
2016
Connie Eaves (C)
University of British Columbia
Disease Team
Marinier
Co-Investigator
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau
30,750
Development of hematopoietic stem cell expanding molecules towards the ideal transplant
Blood
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications.
01/12/2016
31/12/2017
2016
Keith Humphries (C)
University of British Columbia
Disease Team
Marinier
Co-Investigator
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau
13,700
Development of hematopoietic stem cell expanding molecules towards the ideal transplant
Blood
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications.
01/12/2016
31/12/2017
2016
Timothy Kieffer (P)
University of British Columbia
Disease Team
Kieffer
Lead
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman
125,000
Optimizing stem cell derived beta-cell therapy for diabetes
Diabetes
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment.
01/12/2016
31/12/2017
2016
James Johnson (C)
University of British Columbia
Disease Team
Kieffer
Co-Investigator
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman
125,000
Optimizing stem cell derived beta-cell therapy for diabetes
Diabetes
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment.
01/12/2016
31/12/2017
2016
Francis Lynn (C)
University of British Columbia
Disease Team
Kieffer
Co-Investigator
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman
125,000
Optimizing stem cell derived beta-cell therapy for diabetes
Diabetes
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment.
01/12/2016
31/12/2017
2016
Brad Hoffman (C)
University of British Columbia
Disease Team
Kieffer
Co-Investigator
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman
125,000
Optimizing stem cell derived beta-cell therapy for diabetes
Diabetes
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment.
01/12/2016
31/12/2017
2016
Bruce Verchere (P)
University of British Columbia
Disease Team
Verchere
Lead
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings
200,000
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/12/2016
31/12/2017
2016
Francis Lynn (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings
160,000
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/12/2016
31/12/2017
2016
Timothy Kieffer (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings
65,000
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/12/2016
31/12/2017
2016
Megan Levings (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings
65,000
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/12/2016
31/12/2017
2016
Armand Keating (C)
University Health Network
Disease Team
Nagy
Co-Investigator
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor
83,585
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis
Osteoarthritis
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology.
01/12/2016
31/12/2017
2016
Mohit Kapoor (C)
University Health Network
Disease Team
Nagy
Co-Investigator
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor
132,046
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis
Osteoarthritis
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology.
01/12/2016
31/12/2017
2016
Andras Nagy (P)
Sinai Health System
Disease Team
Nagy
Lead
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor
178,992
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis
Osteoarthritis
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology.
01/12/2016
31/12/2017
2016
Gregory Korbutt (C)
University of Alberta
Disease Team
Shapiro
Co-Investigator
James Shapiro, Gregory Korbutt
244,905
Development of a novel stem cell-derived transplant modality for type 1 diabetes
Diabetes
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/12/2016
31/12/2017
2016
James Shapiro (P)
University of Alberta
Disease Team
Shapiro
Lead
James Shapiro, Gregory Korbutt
252,000
Development of a novel stem cell-derived transplant modality for type 1 diabetes
Diabetes
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/12/2016
31/12/2017
2016
Vahab Soleimani (P)
Jewish General Hospital
Disease Team
Soleimani
Lead
Vahab Soleimani
200,000
Interfering niche-related reprogramming of stem cells during aging
Muscle
Adult stem cells are indispensable for tissue homeostasis and repair. In the musculoskeletal system (i.e. skeletal muscle, bone and connective tissue), there is a severe age-related decline in stem cell functionality and tissue repair. This functional decline of stem cells leads to degenerative diseases such as osteoporosis and sarcopenia in the elderly population. Recent experimental evidence suggests that age-related defect in tissue repair could be reversed. However, the molecular mechanisms underlying the plasticity and reversibility of tissue repair in degenerative diseases such as sarcopenia and osteoporosis remains a challenge. Multiple lines of evidence suggest that epigenetic alterations play key roles in the aging process, as cells from aged individuals exhibit reduced area of heterochromatin and loss of repressive histone marks. The reversibility of epigenetic mechanisms by various drugs provides great opportunities to develop urgently needed therapies for many debilitating diseases including the age-related musculoskeletal disorders. However, there is a knowledge gap on how stem cell functionality is lost in degenerative disorders and how aging in general impacts stem cell function and tissue repair. Adult stem cells reside within a defined anatomical location called “the niche” where the stem cell constantly communicates with the surrounding environment and with the neighbouring cells. In patients with degenerative diseases and during aging the environment surrounding the stem cells changes with regards to the cellular content and the chemical signals. Consequently, in the diseased conditions stem cells lose their ability to maintain tissue repair. In this project we aim to determine how changes in the stem cell niche during aging impairs tissue regeneration using hematopoietic, mesenchymal and skeletal muscle stem cells. We hypothesize that the diseased niche alters gene expression profile by modifying the stem cell epigenome. Therefore, we will perform allogeneic stem cell transplantation between young and old mice and map the transcriptional and epigenetic changes that take place as a result of changing niche environment. Using stem cells from three distinct lineages will identify conserved genetic networks that are altered with age. Importantly, by doing reciprocal stem cell transplantation from young to old and vice versa we will determine the “reversible” genetic networks that can be targeted in degenerative musculoskeletal diseases. Finally, we will validate the results in human cells and tissue biopsies to assess the translational potentials. The long-term goal of this project is to develop novel stem cell-based therapies to boost tissue regeneration for musculoskeletal degenerative disorders.
01/12/2016
31/12/2017
2016
Massimiliano Paganelli (P)
CHU Sainte-Justine
Disease Team
Paganelli
Lead
Massimiliano Paganelli
199,982
Treatment of chronic liver failure by stem cell-derived mature liver tissue
Liver Failure
One in ten Canadians is affected by liver disease. The standard of care for liver failure (the common outcome of any progressive liver disease) is liver transplantation, but only 400 transplants are performed each year in Canada for over 5000 liver deaths/year. Thus, there is an urgent need for new therapies capable of replacing liver functions in children and adults with cirrhosis and liver failure. The final aim of this multidisciplinary project is to develop and test an innovative stem cell-based product to restore the lacking liver functions in such patients, improving survival and preventing/treating complications. Our team is composed of a transplant hepatologist expert in stem cell therapy (Dr. Paganelli, CHU Sainte-Justine), two leaders in the field of biomaterials (Dr. Shikanov at University of Michigan, and Dr. Ma, Cornell University), and a molecular oncologist expert in pre-clinical studies (Dr. Petrocca, Boston University). Using our clinical-grade human stem cells we are able to generate 3D cellular microaggregates (organoids) expressing the functions of a healthy liver. We will embed such organoids in a Health Canada-approved synthetic hydrogel we previously developed. Such a biomaterial supports the survival and maturation of the embedded organoids, allowing them to exchange nutrients and substances with the environment and providing complete isolation from the immune system upon implantation into a recipient. Upon encapsulation into this semi-solid hydrogel, our organoids will express most of the functions of a mature liver tissue. Once implanted into a patient with liver failure, such an encapsulated mature liver tissue (EMLT) will be able to purify the patient’ blood from toxic substances and synthesize proteins needed for vital functions, improving survival and preventing severe complications, without the risk of rejection (thus eliminating the need for lifelong immunosuppression). If successful, such a pioneering approach will allow using a single stem cell population to manufacture an off-the-shelf, sustainable product to potentially treat thousands of people. We will conduct thorough pre-clinical studies assessing the efficacy and the short- and long-term safety of this product, in compliance with Health Canada requirements, in order to prepare for an early-phase clinical trial in the medium term (5 years). In collaboration our partners, the EMLT will be patented and options for its commercialization through a spin-off company creation or out-licensing to biopharmaceuticals companies will be explored. If successful, this project will deliver an innovative product to treat liver failure, with the potential of saving hundreds of thousands of patients worldwide.
01/12/2016
31/12/2017
2016
Amy Zarzeczny (C)
University of Regina
Impact Public Policy
Caulfield
Co-Investigator
Timothy Caulfield, Amy Zarzeczny
5,000
Stem cells and misleading marketing claims
ELSI
The marketing of unproven stem cell therapies continues to be a major science and health policy issue. In addition to the hundreds of clinics throughout the world promoting scientifically questionable services, an increasing number of alternative providers are moving into the stem cell sphere (e.g., naturopaths, chiropractors). There is a range of social, scientific harms associated with this marketing trend, including, inter alia, physical harm to patients, financial exploitation, the creation of unrealistic expectations and public confusion about the state of the science. This Impact project will focus on options for curbing misleading marketing practices. To this end, we will: 1) provide an analysis of the claims and language associated with the marketing of unproven stem cell therapies (including the first ever analysis of alternative providers’ claims); 2) develop a comprehensive policy tool kit to address misleading claims (e.g., truth in advertising laws, consumer protection policies, professional norms, etc); and 3) work with professional regulators, consumer advocacy groups, and science policy makers to develop policy strategies, including the commencement of an enforcement test case. This project is a unique and much-needed initiative with the potential to have a real impact and provide actionable policy advice within a short timeframe.
01/12/2016
31/12/2017
2016
Timothy Caulfield (P)
University of Alberta
Impact Public Policy
Caulfield
Lead
Timothy Caulfield, Amy Zarzeczny
45,000
Stem cells and misleading marketing claims
ELSI
The marketing of unproven stem cell therapies continues to be a major science and health policy issue. In addition to the hundreds of clinics throughout the world promoting scientifically questionable services, an increasing number of alternative providers are moving into the stem cell sphere (e.g., naturopaths, chiropractors). There is a range of social, scientific harms associated with this marketing trend, including, inter alia, physical harm to patients, financial exploitation, the creation of unrealistic expectations and public confusion about the state of the science. This Impact project will focus on options for curbing misleading marketing practices. To this end, we will: 1) provide an analysis of the claims and language associated with the marketing of unproven stem cell therapies (including the first ever analysis of alternative providers’ claims); 2) develop a comprehensive policy tool kit to address misleading claims (e.g., truth in advertising laws, consumer protection policies, professional norms, etc); and 3) work with professional regulators, consumer advocacy groups, and science policy makers to develop policy strategies, including the commencement of an enforcement test case. This project is a unique and much-needed initiative with the potential to have a real impact and provide actionable policy advice within a short timeframe.
01/12/2016
31/12/2017
2016
Judy Illes (P)
University of British Columbia
Impact Public Policy
Illes
Lead
Judy Illes
50,000
Decision-making in translation: ugency, access, and evaluation in off-label stem cell interventions
ELSI
The development of health technologies traditionally follows a linear path from discovery through clinical research and, when successful, market approval. In the stem cell arena, however, the path is more multi-pronged than linear, and incorporates different points of access to interventions outside of clinical trials. This is a complex landscape that is especially important for stem cell procedures for as-yet unapproved medical reasons, also known as off-label use. In this study, we are specifically interested in the case of multiple sclerosis (MS) for which, following significant clinical trials activity, patients may be faced with decisions about off-label stem cell transplants. To narrow the gap in this understudied domain of off-label interventions, we will interview MS patients and explore with them the evaluative criteria and decision-making processes that lead them to an off-label bone marrow stem cell transplant over the more conventional alternatives of participating in a clinical trial or waiting for a market-approved therapy. We will deliver the knowledge we gain and its products in the form of evidence-informed resources and recommendations to patients and providers to elevate “informed” in the equation of “informed choices” about investigational stem cell products in the face of chronic, neurodegenerative disease.
01/12/2016
31/12/2017
2016
Amy Zarzeczny (C)
University of Regina
Impact Public Policy
Ogbogu
Co-Investigator
Ubaka Ogbogu, Amy Zarzeczny
10,000
Regulating the future: model policies for emerging stem cell research activities, including research on gene-edited and reconstituted embryos
ELSI
Legislation governing research on human embryos in Canada, including stem cell derivation research, was enacted in 2004. Since then, a number of research techniques not directly addressed in the legislation have been described in the scientific literature. Two such techniques – the creation and use of genetically modified human embryos for research and the patterning of human induced pluripotent stem cells in a manner that may resemble post-implantation embryos – raise pressing questions both about the legality of these emerging techniques and about the appropriateness of current governance frameworks. More specifically, the growing interest in these emerging avenues of research highlight the need to reconsider Canada’s regulatory framework in the context of current scientific realities and to evaluate whether it adequately and appropriately addresses and balances the promotion of scientific and clinical progress with other key policy imperatives. Through a multi-disciplinary policy workshop supported by legal and policy analyses, this project will investigate two main questions: (1) whether, and, in what manner, should Canadian embryo and related research regulations be updated to reflect current research realities and scientific advances? and (2) what specific rules and governance mechanisms are required to ensure the ethical conduct of novel embryo-based research activities? The project will produce a consensus-based model policy and governance framework for regulating embryo research advances in Canada, academic publications and “policy briefing notes” designed for particular audiences, including legislators, scientists, media and the public. The project outcomes will have direct relevance to issues and research activities that affect or involve many Canadians, including scientists, governments and patients.
01/12/2016
31/12/2017
2016
Ubaka Ogbogu (P)
University of Alberta
Impact Public Policy
Ogbogu
Lead
Ubaka Ogbogu, Amy Zarzeczny
40,000
Regulating the future: model policies for emerging stem cell research activities, including research on gene-edited and reconstituted embryos
ELSI
Legislation governing research on human embryos in Canada, including stem cell derivation research, was enacted in 2004. Since then, a number of research techniques not directly addressed in the legislation have been described in the scientific literature. Two such techniques – the creation and use of genetically modified human embryos for research and the patterning of human induced pluripotent stem cells in a manner that may resemble post-implantation embryos – raise pressing questions both about the legality of these emerging techniques and about the appropriateness of current governance frameworks. More specifically, the growing interest in these emerging avenues of research highlight the need to reconsider Canada’s regulatory framework in the context of current scientific realities and to evaluate whether it adequately and appropriately addresses and balances the promotion of scientific and clinical progress with other key policy imperatives. Through a multi-disciplinary policy workshop supported by legal and policy analyses, this project will investigate two main questions: (1) whether, and, in what manner, should Canadian embryo and related research regulations be updated to reflect current research realities and scientific advances? and (2) what specific rules and governance mechanisms are required to ensure the ethical conduct of novel embryo-based research activities? The project will produce a consensus-based model policy and governance framework for regulating embryo research advances in Canada, academic publications and “policy briefing notes” designed for particular audiences, including legislators, scientists, media and the public. The project outcomes will have direct relevance to issues and research activities that affect or involve many Canadians, including scientists, governments and patients.
01/12/2016
31/12/2017
2018
Jean Roy (P)
Hôpital Maisonneuve-Rosemont
Clinical Trial Awards
Roy
Lead
Jean Roy
500,000
Allogeneic stem cell transplant using UM171 expanded cord bloods for patients with high-risk multiple myeloma
Blood, Myeloma
Multiple myeloma, the second most common blood cancer in Canada, remains incurable with a life expectancy of 5-6 years. Myeloma patients with advanced disease, chromosome abnormalities, myeloma cells in the blood or who are unresponsive to initial therapy have an even worse survival of approximately 3 years. To date, the only curative option for multiple myeloma is an allogeneic stem cell transplant (a transplant from a family or unrelated donor). However, allogeneic transplant is associated with serious side effects, the most significant being the donor cells attacking various recipient’s organs, a condition called graft-versus-host disease, leading to an early mortality of 10-20%. In patients who survive, long-term immune complications (80%) and relapse (50%) remain frequent. Clearly, allogeneic transplant needs to be improved in order to cure more patients.
In this study, we propose to use the unique properties of cord blood in order to make allogeneic transplant safer and more successful for myeloma patients. Cord blood use is associated with a much lower incidence of immune complications while having strong anti-cancer activity. It has been used for decades in children, less so in adults due to small number of stem cells in the graft leading to slow blood counts recovery after transplant. Recently, a novel molecule discovered by Canadian scientists in Montreal, UM171, has been shown to increase the number of stem cells and anti-cancer immune cells in laboratory, with promising results in the first 17 adults transplanted. In this study, cord bloods will be cultured in laboratory then infused in 10 patients with myeloma at higher risk of relapse. We expect a decreased incidence of immune complications and lower incidence of relapse. If successful, allogeneic transplant using cord bloods expanded with UM171 could become the treatment of choice for patients with poor prognosis multiple myeloma in the near future.
01/04/2018
28/02/2019
2018
James Shapiro (P)
University of Alberta
Clinical Trial Awards
Shapiro
Lead
James Shapiro
500,000
Pancreatic Progenitor Cell Therapy: Solving Supply and Survival Issues of Islet Cell Transplantation for T1DM
Diabetes
The proposed project is aimed at treating, and functionally curing, type 1 diabetes mellitus (T1D) patients with embryonic stem cell-derived islet replacement therapy. There is no known way to prevent or cure T1D. Since the primary pathogenesis of T1D is the loss of the insulin-producing beta cells in the pancreas, it is a good candidate for cell replacement therapy. Cadaver islet transplantation represents clinical proof-of-concept for this approach, and the pluripotent stem cell-based technologies have the potential to solve the current shortage of material, as well as to provide reliable, high quality implantable material delivered in a safe and broadly applicable format.
The VC01 trial is designed to target all insulin-utilizing patients, including at least 270,000 Canadians and 40 million worldwide; the VC02 trial targets 10% T1D patients at high risk of acute complications. Both use the same pancreatic endoderm cells (PEC-01). These patients suffer insulin injection, hypoglycemia unawareness, and severe hypoglycemic episodes, which can be sometimes fatal. Medical care costs for people with diabetes are more than two times higher than for those without diabetes.
ViaCyte has made great progress in developing a practical islet cell replacement therapy, and the Edmonton Team has collaborated with them both in pre-clinical and clinical studies previously (VC01 cohort 1 and VC02 cohort 1 – SCN funded). The proposal herein is to perform clinical testing of an improved VC01 delivery device to demonstrate clinically relevant efficacy, and the VC02 in high-risk T1D patients (cohort 2) to assess safety and efficacy.
The project is likely the most expedient way to assess this therapy in T1D patients with the most urgent unmet medical need. VC01/VC02 products could transform and save the lives of countless people suffering with T1D, and eventually minimize the resource stress placed on our healthcare system.
01/04/2018
28/02/2019
2018
Duncan Stewart (P)
Ottawa Hospital Research Institute
Clinical Trial Awards
Stewart
Lead
Duncan Stewart
500,000
ENhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT- AMI)
Cardiac
Rationale: Patients with a large area of damaged heart muscle after a heart attack have a high risk for heart failure and death. Cell-based gene therapy could restore working muscle in regions that otherwise would form only scar tissue, and lead to better heart repair and function.
Purpose: The primary objectives of the ENACT-AMI trial are to determine whether the administration of a patient’s own (autologous) Endothelial Progenitor Cells (EPCs) is safe and effective in improving cardiac function following large heart attack, and whether the use of cells that are genetically engineered by adding extra copies of a gene that is critical for blood vessel function and repair, namely endothelial Nitric Oxide Synthase (eNOS), is superior to non-modified cells. A secondary objective is to determine whether the benefit of EPC therapy depends on the timing of cell delivery (5-15 days versus 16-30 days post-STEMI).
Novel aspects: The use of the patient’s own cells avoids the immunological rejection that occurs with transplantation of cells from other individuals, but is greatly hampered by the fact that the reparative activities of stem and progenitor cells are negatively influenced by the host risk factors that lead to heart disease in the first place, namely advanced age, high cholesterol, diabetes and so forth. We have shown that adding extra copies of the eNOS gene (which protects blood vessels and promotes their growth and repair) can restore the activity of EPCs from heart patients by almost 90%. ENACT-AMI is the first clinical trial in the world to include a strategy designed to enhance the function of a patient’s own cells, and the first to use combination gene and cell therapy, for the treatment of heart disease.
Benefits to Canadians and Canada: While outcomes after heart attacks have greatly improved with the advent of modern therapies to open up the blocked coronary artery (reperfusion therapy), about 20% of patients fail to receive the expected benefits of reperfusion therapy, and face the consequences of large heart damage and subsequent heart failure. Should gene-enhanced EPCs provide an effective adjunctive treatment for these patients, this would avoid a high individual burden of chronic debilitating disease, while reducing the high costs to the health care system which in Canada totals $2.8 billion per year for heart failure (heartandstroke.ca/heartreport). If successful, ENACT investigators are well positioned to disseminate such a therapy across Canada though CellCAN, a unique network of cell manufacturing facilities across Canada.
01/04/2018
28/02/2019
2018
Timothy Kieffer (P)
University of British Columbia
Impact Clinical Translation and Accelerator
Kieffer
Lead
Timothy Kieffer
100,000
Assessment of Cell Maturation and Function in Subcutaneous Macroencapsulation Devices in Rodents
Diabetes
01/04/2018
28/02/2019
2018
Zachary Laksman (P)
University of British Columbia
Impact Clinical Translation and Accelerator
Laksman
Lead
Zachary Laksman, Glen Tibbits
90,000
High throughput novel drug screening in human tissue model of atrial fibrillation
Cardiac Disease
01/04/2018
28/02/2019
2018
Glen Tibbits (C)
Simon Fraser University
Impact Clinical Translation and Accelerator
Laksman
Co-Investigator
Zachary Laksman, Glen Tibbits
10,000
High throughput novel drug screening in human tissue model of atrial fibrillation
Cardiac Disease
01/04/2018
28/02/2019
2018
Lauralyn McIntyre (P)
Ottawa Hospital Research Institute
Impact Clinical Translation and Accelerator
McIntyre
Lead
Lauralyn McIntyre
100,000
Cellular Immunotherapy for Septic Shock (CISS2): A Phase II Multicentre Clinical Trial
Sepsis
01/04/2018
28/02/2019
2018
Bernard Thébaud (P)
Ottawa Hospital Research Institute
Impact Clinical Translation and Accelerator
Thébaud
Lead
Bernard Thébaud
99,905
Endothelial Progenitor Cell-derived Therapies for Neonatal Pulmonary Hypertension
Lung Disease
01/04/2018
28/02/2019
2018
Glen Tibbits (P)
Simon Fraser University
Impact Clinical Translation and Accelerator
Tibbits
Lead
Glen Tibbits
99,500
Developing an hiPSC-CM based protocol to investigate SIDS-implicated sudden cardiac arrest in infants
Cardiac
01/04/2018
28/02/2019
2018
Xudong Cao (C)
University of Ottawa
Impact Clinical Translation and Accelerator
Tsai
Co-Investigator
Xudong Cao, Eve Tsai
28,915
Translating an animal endogenous stem/progenitor cell repair strategy for stroke to humans
Brain injury
01/04/2018
28/02/2019
2018
Eve Tsai (P)
Ottawa Hospital Research Institute
Impact Clinical Translation and Accelerator
Tsai
Lead
Xudong Cao, Eve Tsai
71,085
Translating an animal endogenous stem/progenitor cell repair strategy for stroke to humans
Brain injury
01/04/2018
28/02/2019
2018
Derrick Rancourt (P)
University of Calgary
Impact Commercialization
Rancourt
Lead
Derrick Rancourt
100,000
Enhancing the Efficiency of Genome Engineering in Human Pluripotent Stem Cells
Genome Engineering
01/04/2018
28/02/2019
2018
Peter Zandstra (P)
University of British Columbia
Impact Commercialization
Zandstra
Lead
Peter Zandstra
100,000
A robust, quantitative, and high-throughput assay to rapidly characterize human induced pluripotent stem cells.
Untreatable retinal degeneration dramatically affects millions of people, both young and old. In Canada, vision loss incurs the highest direct healthcare costs of any disease group – $33,000/patient/year. Globally, age-related macular degeneration (AMD) has an economic cost of over $350 billon (USD) annually, let alone the many other diseases that cause untreatable retinal degeneration.
Fortunately, stem-cell-based therapeutics are rapidly approaching the level of efficacy, safety, and economic scalability needed for clinical adoption. However, a central barrier remains for vision to be restored to the vast majority of patients that suffer from advanced retinal degeneration, that both the retinal pigment epithelium (RPE) and photoreceptor (PR) layers – co-dependant layers – must be regenerated. Unfortunately, these graft cells have not been shown to self-stratify and thus cannot be simply co-injected. Current best graft delivery efforts use scaffolds or sheets, which often do more harm than good or provide negligible coverage.
We have developed a cell-based therapeutic that addresses this translational roadblock by non-invasively inducing (via proprietary technology) dual-graft (RPE+PR) suspension injected into the subretinal space into polarized – stratified – layers with extensive fundus-coverage. This is achieved using standard clinical techniques and infrastructure, which reduces costs and increases likelihood of clinical adoption. We have attained dual-graft stratification in live rabbit trials. Despite these promising graft-architecture data, further optimization through larger-scale animal trials is required to obtain the efficacy and safety data to attract the considerable investment and partnerships needed to initiate clinical trials in Canada. Our core aims are: 1) generating dual-graft stratification in clinically relevant: graft (stem-cell-derived) and hosts (rabbits that have lost their PR layer), and 2) establishing graft integration (useful synapse formation) and vision benefit. In preparation for commercialization, our multidisciplinary team, representing three Canadian universities (UBC, SFU, and DU), have spun-off the company, VisuCyte Therapeutics Inc., which is being incubated at UBC.
01/04/2018
28/02/2019
2018
Shirley Mei (C)
Ottawa Hospital Research Institute
Disease Team
McIntyre
Co-Investigator
Lauralyn McIntyre, Shirley Mei
44,278
Cellular Immunotherapy for Septic Shock (CISS2): A phase II multicentre clinical trial
Sepsis
Septic shock is a common and devastating illness in the intensive care unit (ICU) accounting for approximately 20% of admissions, of which 30-40% will die. Survivors suffer long-term impairment in function and reduced quality of life (QOL). Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy. Mesenchymal stem cells (MSCs) represent a novel treatment and have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death in septic animals.
Our team is the first in the World to have completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in acutely ill patients and that a randomized controlled trial (RCT) is feasible. We are now moving to a Phase II RCT at several Canadian academic hospitals. This RCT will continue to evaluate safety and assess if there are strong signals for clinical benefit and determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective
Our multi-disciplinary team brings extensive experience in basic science, translational research, and early and late-phase clinical trialists. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a potent cryopreserved MSC product and to ensure its efficient distribution to participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support an international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and QOL of survivors of this devastating illness.
01/04/2018
28/02/2019
2018
Lauralyn McIntyre (P)
Ottawa Hospital Research Institute
Disease Team
McIntyre
Lead
Lauralyn McIntyre, Shirley Mei
155,722
Cellular Immunotherapy for Septic Shock (CISS2): A phase II multicentre clinical trial
Sepsis
Septic shock is a common and devastating illness in the intensive care unit (ICU) accounting for approximately 20% of admissions, of which 30-40% will die. Survivors suffer long-term impairment in function and reduced quality of life (QOL). Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy. Mesenchymal stem cells (MSCs) represent a novel treatment and have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death in septic animals.
Our team is the first in the World to have completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in acutely ill patients and that a randomized controlled trial (RCT) is feasible. We are now moving to a Phase II RCT at several Canadian academic hospitals. This RCT will continue to evaluate safety and assess if there are strong signals for clinical benefit and determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective
Our multi-disciplinary team brings extensive experience in basic science, translational research, and early and late-phase clinical trialists. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a potent cryopreserved MSC product and to ensure its efficient distribution to participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support an international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and QOL of survivors of this devastating illness.
01/04/2018
28/02/2019
2018
Cindi Morshead (C)
University of Toronto
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,223
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Jing Wang (C)
Ottawa Hospital Research Institute
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Paul Frankland (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
David Kaplan (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Ann Yeh (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Doug Munoz (C)
Queen's University
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Donald Mabbott (C)
The Hospital for Sick Children
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Freda Miller (P)
The Hospital for Sick Children
Disease Team
Miller
Lead
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,222
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Wolfram Tetzlaff (C)
University of British Columbia
Disease Team
Miller
Co-Investigator
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff
22,223
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair
Neural
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/04/2018
28/02/2019
2018
Massimiliano Paganelli (P)
CHU Sainte-Justine
Disease Team
Paganelli
Lead
Massimiliano Paganelli
100,000
Safety and efficacy of stem cell- derived Encapsulated Liver Tissue to treat liver failure without immunosuppression
Liver Failure
One in ten Canadians is affected by liver disease. The standard of care for liver failure (the common outcome of any progressive liver disease) is liver transplantation, but only 400 transplants are performed each year in Canada for over 5000 liver deaths/year. Thus, there is an urgent need for new therapies capable of replacing liver functions in children and adults with liver failure. Thanks to a grant from the Stem Cell Network and to a team of internationally-renowned experts, in less than one year we developed an innovative stem cell-derived product capable of effectively performing the functions of the human liver. The final aim of this multidisciplinary project is to develop such a product into a treatment to restore the lacking liver functions in patients with liver failure, improving survival and preventing/treating complications. We will thoroughly assess the potential of our stem cell-derived product (what we call the encapsulated liver tissue, or ELT) to purify the patients’ blood from toxic substances and synthesize proteins needed for vital functions, improving survival and preventing severe complications, without the risk of rejection (eliminating the need for lifelong immunosuppression). If successful, at the end of the study we will dispose of a safe and effective off-the-shelf, implantable product to potentially treat thousands of people with liver failure. We will then conduct thorough pre-clinical studies, in compliance with Health Canada requirements, in order to prepare for an early-phase clinical trial in the medium term (3 years). We already protected this intellectual property and, in collaboration with our partners, we will work to translate the ELT to the industry through a start-up company creation or out-licensing. If successful, this project will deliver an innovative product to treat acute, chronic or acute-on-chronic liver failure without immunosuppression, with the potential of saving hundreds of thousands of patients worldwide.
01/04/2018
28/02/2019
2018
Gregory Korbutt (C)
University of Alberta
Disease Team
Shapiro
Co-Investigator
James Shapiro, Gregory Korbutt
50,000
Development of a novel stem cell- derived transplant modality for type 1 diabetes
Diabetes
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/04/2018
28/02/2019
2018
James Shapiro (P)
University of Alberta
Disease Team
Shapiro
Lead
James Shapiro, Gregory Korbutt
50,000
Development of a novel stem cell- derived transplant modality for type 1 diabetes
Diabetes
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/04/2018
28/02/2019
2018
Bruce Verchere (P)
University of British Columbia
Disease Team
Verchere
Lead
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings
80,000
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/04/2018
28/02/2019
2018
Francis Lynn (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings
80,000
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/04/2018
28/02/2019
2018
Timothy Kieffer (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings
20,000
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/04/2018
28/02/2019
2018
Megan Levings (C)
University of British Columbia
Disease Team
Verchere
Co-Investigator
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings
20,000
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/04/2018
28/02/2019
2018
Jean-François Bouchard (C)
Université de Montréal
Disease Team
Bernier
Co-Investigator
Gilbert Bernier, May Griffith, Jean-François Bouchard
25,000
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques
Ocular
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial.
01/04/2018
28/02/2019
2018
May Griffith (C)
Université de Montréal
Disease Team
Bernier
Co-Investigator
Gilbert Bernier, May Griffith, Jean-François Bouchard
25,000
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques
Ocular
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial.
01/04/2018
28/02/2019
2018
Gilbert Bernier (P)
Hôpital Maisonneuve-Rosemont
Disease Team
Bernier
Lead
Gilbert Bernier, May Griffith, Jean-François Bouchard
150,000
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques
Ocular
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial.
01/04/2018
28/02/2019
2018
Timothy Caulfield (P)
University of Alberta
Impact Public Policy
Caulfield
Lead
Timothy Caulfield
40,000
The Next Step: Specific Strategies for Addressing the Marketing of Unproven Stem Cell Therapies
Unproven therapies
01/04/2018
28/02/2019
2018
Bartha Knoppers (P)
McGill University
Impact Public Policy
Knoppers
Lead
Bartha Knoppers
39,736
Reforming Canadian Stem Cell Policy: Moving Beyond the Assisted Human Reproduction Act (AHRA)
ELSI
01/04/2018
28/02/2019
2018
Eric Marsault (C)
Université de Sherbrooke
Impact Translation
Bentzinger
Co-Investigator
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault
9,000
Apelinergic Compounds for the treatment of muscular dystrophy
Muscle dystrophy
01/04/2018
28/02/2019
2018
Mannix Auger-Messier (C)
Université de Sherbrooke
Impact Translation
Bentzinger
Co-Investigator
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault
7,000
Apelinergic Compounds for the treatment of muscular dystrophy
Muscle dystrophy
01/04/2018
28/02/2019
2018
Florian Bentzinger (P)
Université de Sherbrooke
Impact Translation
Bentzinger
Lead
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault
83,000
Apelinergic Compounds for the treatment of muscular dystrophy
Muscle dystrophy
01/04/2018
28/02/2019
2018
Mick Bhatia (P)
McMaster University
Impact Translation
Bhatia
Lead
Mick Bhatia
100,000
Identification of kinases and their target substrates in early human PSC specification
Kinases
01/04/2018
28/02/2019
2018
Nicolas Dumont (P)
CHU Sainte-Justine
Impact Translation
Dumont
Lead
Nicolas Dumont
100,000
Targeting muscle stem cells to mitigate Duchenne muscular dystrophy
Muscle dystrophy
01/04/2018
28/02/2019
2018
John Hassell (P)
McMaster University
Impact Translation
Hassell
Lead
John Hassell
99,500
HTR5A as a target for anticancer stem cell drug discovery
Breast Cancer
01/04/2018
28/02/2019
2020
Timothy Kieffer (C)
University of British Columbia
Accelerating Clinical Translation
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
40,000
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/01/2020
31/01/2022
2020
Megan Levings (C)
University of British Columbia
Accelerating Clinical Translation
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
40,000
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/01/2020
31/01/2022
2020
Francis Lynn (C)
University of British Columbia
Accelerating Clinical Translation
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
228,000
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/01/2020
31/01/2022
2020
Bruce Verchere (P)
University of British Columbia
Accelerating Clinical Translation
Verchere
Lead
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
292,000
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes
Diabetes
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today.
01/01/2020
31/01/2022
2020
Nilesh Ghugre (C)
University of Toronto
Accelerating Clinical Translation
Laflamme
Co-Investigator
Michael Laflamme, Graham Wright, Nilesh Ghugre
74,592
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells
Cardiac
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine.
01/01/2020
31/01/2022
2020
Graham Wright (C)
University of Toronto
Accelerating Clinical Translation
Laflamme
Co-Investigator
Michael Laflamme, Graham Wright, Nilesh Ghugre
22,704
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells
Cardiac
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine.
01/01/2020
31/01/2022
2020
Michael Laflamme (P)
University Health Network
Accelerating Clinical Translation
Laflamme
Lead
Michael Laflamme, Graham Wright, Nilesh Ghugre
502,389
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells
Cardiac
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine.
01/01/2020
31/01/2022
2020
Zachary Laksman (P)
University of British Columbia
Accelerating Clinical Translation
Laksman
Lead
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham
292,000
Pipeline towards stem cell driven personalized medicine for atrial fibrillation
Cardiac; atrial fibrilation
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation.
01/01/2020
31/01/2022
2020
Gordon Keller (C)
University Health Network
Accelerating Clinical Translation
Laksman
Co-Investigator
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham
30,000
Pipeline towards stem cell driven personalized medicine for atrial fibrillation
Cardiac
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation.
01/01/2020
31/01/2022
2020
Glen Tibbits (C)
Simon Fraser University
Accelerating Clinical Translation
Laksman
Co-Investigator
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham
152,000
Pipeline towards stem cell driven personalized medicine for atrial fibrillation
Cardiac
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation.
01/01/2020
31/01/2022
2020
Liam Brunham (C)
University of British Columbia
Accelerating Clinical Translation
Laksman
Co-Investigator
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham
112,000
Pipeline towards stem cell driven personalized medicine for atrial fibrillation
Cardiac
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation.
01/01/2020
31/01/2022
2020
Greg Korbutt (C)
University of Alberta
Accelerating Clinical Translation
Nostro
Co-Investigator
Cristina Nostro, Andrew Pepper, Greg Korbutt
150,000
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment
Diabetes
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/01/2020
31/01/2022
2020
Andrew Pepper (C)
University of Alberta
Accelerating Clinical Translation
Nostro
Co-Investigator
Cristina Nostro, Andrew Pepper, Greg Korbutt
150,000
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment
Diabetes
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/01/2020
31/01/2022
2020
Cristina Nostro (P)
University Health Network
Accelerating Clinical Translation
Nostro
Lead
Cristina Nostro, Andrew Pepper, Greg Korbutt
300,000
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment
Diabetes
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials.
01/01/2020
31/01/2022
2020
Vincent-Philippe Lavallee (C)
Université de Montréal
Accelerating Clinical Translation
Sauvageau
Co-Investigator
Guy Sauvageau, Vincent-Philippe Lavallee
28,200
UM171 expansion improves the curative attributes of bone marrow stem cell grafts
Blood
Hematopoietic stem cells (HSC) transplantation is one of the most effective therapeutic strategies for patients with hematological malignancies. Largely supported by the SCN, our group of collaborators developed a cord blood (CB)-derived HSC expansion solution that includes the UM171 molecule and a Fed-batch HSC expansion system both of which combined have had major impact on CB transplantation. Indeed, to date more than 50 patients have received UM171/Fed-batch-expanded CB grafts with very promising results including low incidence of transplant-related mortality, chronic graft versus host disease and relapse rate. One of the key attributes of UM171/Fed-batch expanded CB is the inclusion of large numbers of immuno-modulatory cells, which we believe contribute to the success of these transplants. With the view of extending these attributes to bone marrow (BM) transplants, which are much more numerous than CB and hence further increasing the clinical impact of this procedure, we now propose three well-defined experimental aims:
First, we will develop a large-scale manufacturing process that will enable the production of UM171 expanded bone marrow grafts for our future clinical trial.
Second, considering our recent work showing that UM171 treatment of BM HSCs results in a marked increase in their ability to repopulate the thymus of humanized mice, we now intend to carefully characterize this important effect and verify if it is preserved in BM grafts derived from older donors which are typically associated with poor lymphoid function and clinical outcome. This will enable us to determine the optimal donor age in which this unique effect of UM171 is found and refine the design of our future clinical trial.
Third, we plan to characterize the cellular subpopulations in UM171-expanded BM grafts using state of the art technology, including CITE-Seq and preclinical functional assays. These essential preclinical studies will provide some understanding of the clinical impact of UM171 transplants and address regulatory issues associated with graft expansion.
These three aims represent an essential prerequisite of an optimal future clinical trial of UM171 bone marrow stem cell expansion whose final design will also be drafted using support and results from this grant.
01/09/2020
28/02/2022
2020
Guy Sauvageau (P)
Université de Montréal
Accelerating Clinical Translation
Sauvageau
Lead
Guy Sauvageau, Vincent-Philippe Lavallee
371,800
UM171 expansion improves the curative attributes of bone marrow stem cell grafts
Blood; leukemia
Hematopoietic stem cells (HSC) transplantation is one of the most effective therapeutic strategies for patients with hematological malignancies. Largely supported by the SCN, our group of collaborators developed a cord blood (CB)-derived HSC expansion solution that includes the UM171 molecule and a Fed-batch HSC expansion system both of which combined have had major impact on CB transplantation. Indeed, to date more than 50 patients have received UM171/Fed-batch-expanded CB grafts with very promising results including low incidence of transplant-related mortality, chronic graft versus host disease and relapse rate. One of the key attributes of UM171/Fed-batch expanded CB is the inclusion of large numbers of immuno-modulatory cells, which we believe contribute to the success of these transplants. With the view of extending these attributes to bone marrow (BM) transplants, which are much more numerous than CB and hence further increasing the clinical impact of this procedure, we now propose three well-defined experimental aims:
First, we will develop a large-scale manufacturing process that will enable the production of UM171 expanded bone marrow grafts for our future clinical trial.
Second, considering our recent work showing that UM171 treatment of BM HSCs results in a marked increase in their ability to repopulate the thymus of humanized mice, we now intend to carefully characterize this important effect and verify if it is preserved in BM grafts derived from older donors which are typically associated with poor lymphoid function and clinical outcome. This will enable us to determine the optimal donor age in which this unique effect of UM171 is found and refine the design of our future clinical trial.
Third, we plan to characterize the cellular subpopulations in UM171-expanded BM grafts using state of the art technology, including CITE-Seq and preclinical functional assays. These essential preclinical studies will provide some understanding of the clinical impact of UM171 transplants and address regulatory issues associated with graft expansion.
These three aims represent an essential prerequisite of an optimal future clinical trial of UM171 bone marrow stem cell expansion whose final design will also be drafted using support and results from this grant.
01/09/2020
28/02/2022
2020
Greg Korbutt (C)
University of Alberta
Accelerating Clinical Translation
Shapiro
Co-Investigator
James Shapiro, Greg Korbutt
49,750
Autologous Patient-derived Islets from Induced Pluripotent Stem Cells (iPSC): The Next Generation Diabetes Therapy
Diabetes
The University of Alberta under Dr. Shapiro’s direction has established a global presence as a leader in islet transplantation for T1D. Islet transplantation has a proven track record of success in effectively eradicating the risk of hypoglycemia while rendering many patients insulin free for variable periods. The downside, however, is the need for life-long immunosuppression, and a limited ability to isolate a full normal complement of islet mass to engraft in the recipient, as well as an insufficient organ donor pool requirement to meet the demand if indications for islet transplantation move beyond the select few with ‘brittle’ control. In contrast, human induced pluripotent stem cells (iPSCs) offer considerable promise as a renewable autologous β-cell source for transplantation without the need for chronic life-long immunosuppression. Human iPSC-derived β-cells have previously been shown to effectively control blood sugar and reverse diabetes in mice. In this proposal, we aim to validate human-derived autologous expanded iPSCs for generating β-like cells sourced from normal controls, patients with T1D, T2D and those with surgical diabetes after TP using established protocols, without the need for maintenance immune suppression. The purpose of using subjects with surgical diabetes, as controls, is to avoid potential initial challenges with either autoimmunity (in T1D) or insulin resistance (in T2D). The aim of the project is to evaluate iPSC-derived immature progenitor cells versus more mature functional β-like cells for scale-up. The ultimate goal is to establish GMP manufacturing processes to initiate a clinical trial for subcutaneous (phase 1 safety) followed by intraportal (phase 1/2 safety + efficacy) transplantation of autologous self-expanded β-like cells into TP patients, without immunosuppression, succeeded by transplantation in T2D and T1D patients.
The proposal shows strong potential for developing autologous cell therapy for the curative treatment of diabetes. Efforts to scale up GMP-grade iPSC-derived β-like cells will impart social benefit to Canadians and significantly relieve the current ever-increasing economic burden of diabetes healthcare in Canada. Our project team includes excellent researchers, clinicians and highly skilled technicians with stem cell expertise. In addition, we will collaborate with experts in islet regeneration, molecular genetics, transplant immunology, and GMP cell manufacturing.
01/09/2020
28/02/2022
2020
James Shapiro (P)
University of Alberta
Accelerating Clinical Translation
Shapiro
Lead
James Shapiro, Greg Korbutt
350,250
Autologous Patient-derived Islets from Induced Pluripotent Stem Cells (iPSC): The Next Generation Diabetes Therapy
Diabetes
The University of Alberta under Dr. Shapiro’s direction has established a global presence as a leader in islet transplantation for T1D. Islet transplantation has a proven track record of success in effectively eradicating the risk of hypoglycemia while rendering many patients insulin free for variable periods. The downside, however, is the need for life-long immunosuppression, and a limited ability to isolate a full normal complement of islet mass to engraft in the recipient, as well as an insufficient organ donor pool requirement to meet the demand if indications for islet transplantation move beyond the select few with ‘brittle’ control. In contrast, human induced pluripotent stem cells (iPSCs) offer considerable promise as a renewable autologous β-cell source for transplantation without the need for chronic life-long immunosuppression. Human iPSC-derived β-cells have previously been shown to effectively control blood sugar and reverse diabetes in mice. In this proposal, we aim to validate human-derived autologous expanded iPSCs for generating β-like cells sourced from normal controls, patients with T1D, T2D and those with surgical diabetes after TP using established protocols, without the need for maintenance immune suppression. The purpose of using subjects with surgical diabetes, as controls, is to avoid potential initial challenges with either autoimmunity (in T1D) or insulin resistance (in T2D). The aim of the project is to evaluate iPSC-derived immature progenitor cells versus more mature functional β-like cells for scale-up. The ultimate goal is to establish GMP manufacturing processes to initiate a clinical trial for subcutaneous (phase 1 safety) followed by intraportal (phase 1/2 safety + efficacy) transplantation of autologous self-expanded β-like cells into TP patients, without immunosuppression, succeeded by transplantation in T2D and T1D patients.
The proposal shows strong potential for developing autologous cell therapy for the curative treatment of diabetes. Efforts to scale up GMP-grade iPSC-derived β-like cells will impart social benefit to Canadians and significantly relieve the current ever-increasing economic burden of diabetes healthcare in Canada. Our project team includes excellent researchers, clinicians and highly skilled technicians with stem cell expertise. In addition, we will collaborate with experts in islet regeneration, molecular genetics, transplant immunology, and GMP cell manufacturing.
01/09/2020
28/02/2022
2020
Glen Tibbits (P)
Simon Fraser University
Accelerating Clinical Translation
Tibbits
Lead
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem
217,415
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT)
Cardiac
Rare disease status
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT.
01/09/2020
28/02/2022
2020
Francis Lynn (C)
University of British Columbia
Accelerating Clinical Translation
Tibbits
Co-Investigator
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem
33,210
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT)
Cardiac
Rare disease status
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT.
01/09/2020
28/02/2022
2020
Shubhayan Sanatani (C)
University of British Columbia
Accelerating Clinical Translation
Tibbits
Co-Investigator
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem
51,450
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT)
Cardiac
Rare disease status
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT.
01/09/2020
28/02/2022
2020
Filip van Petegem (C)
University of British Columbia
Accelerating Clinical Translation
Tibbits
Co-Investigator
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem
97,875
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT)
Cardiac
Rare disease status
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT.
01/09/2020
28/02/2022
2020
Paul Frankland (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,333
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
David Kaplan (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,333
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Donald Mabbott (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
25,000
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Freda Miller (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,333
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Cindi Morshead (C)
University of Toronto
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,333
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Douglas Munoz (C)
Queen's University
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
25,000
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Jiwon Oh (C)
University of Toronto
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
5,000
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Jing Wang (C)
Ottawa Hospital Research Institute
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,332
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Ann Yeh (P)
The Hospital for Sick Children
Accelerating Clinical Translation
Yeh
Lead
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
25,000
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural; ms
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Wolfram Tetzlaff (C)
University of British Columbia
Accelerating Clinical Translation
Yeh
Co-Investigator
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff
53,333
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS
Neural
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
01/09/2020
28/02/2022
2020
Jonas Mattsson (C)
University Health Network
Accelerating Clinical Translation
Zúñiga-Pflücker
Co-Investigator
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
80,000
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm)
Blood
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients.
01/09/2020
28/02/2022
2020
Donna Wall (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Zúñiga-Pflücker
Co-Investigator
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
80,000
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm)
Blood
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients.
01/09/2020
28/02/2022
2020
Juan Carlos Zúñiga-Pflücker (P)
Sunnybrook Research Institute
Accelerating Clinical Translation
Zúñiga-Pflücker
Lead
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
240,000
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm)
Blood; immunotherapies for cancer
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients.
01/09/2020
28/02/2022
2020
Manuel Caruso (C)
Université Laval
Accelerating Clinical Translation
Germain
Co-Investigator
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso
12,000
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction
Skin
Rare disease status
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/09/2020
28/02/2022
2020
Bartha Knoppers (C)
McGill University
Accelerating Clinical Translation
Germain
Co-Investigator
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso
30,000
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction
Skin
Rare disease status
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/09/2020
28/02/2022
2020
Elena Pope (C)
The Hospital for Sick Children
Accelerating Clinical Translation
Germain
Co-Investigator
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso
6,000
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction
Skin
Rare disease status
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/09/2020
28/02/2022
2020
Lucie Germain (P)
Université Laval
Accelerating Clinical Translation
Germain
Lead
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso
352,000
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction
Skin; epidermolysis bullosa
Rare disease status
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/09/2020
28/02/2022
2020
Sandra Cohen (P)
Hôpital Maisonneuve-Rosemont
Advancing Clinical Trials
Cohen
Lead
Sandra Cohen
1,600,000
UM171-Expanded Cord Blood Grafts Offer Potential Cure for Very High-Risk Leukemia Patients
Blood; leukemia
Stem cell transplantation is one of the best therapies to cure blood cancers. Unfortunately, the risks of relapse (≈30%) and of dying from complications related to the transplant (also known as transplant related mortality ≈20%) remain high. Usually, patients receive bone marrow or blood stem cells from a related or unrelated compatible donor. Cord blood (CB) is an attractive alternative stem cell source due to its unique properties, including low risk of chronic graft-versus-host disease (GVHD) and relapse. A lower risk of chronic GVHD is very important as it is the major determinant of long-term quality of life after a transplant. However, these advantages of CB transplants are offset by the limited cell dose (i.e. small cords), which results in delayed recovery of blood counts, increased infections, prolonged hospitalization and early mortality. We have now completed a first clinical trial to test 2 Canadian discoveries, the UM171 small molecule developed in G. Sauvageau and A. Marinier’s laboratories (University of Montreal) and an optimized culture system from P. Zandstra’s laboratory (University of British Columbia). Combined, these ground-breaking technologies increase the number of stem cells in CB and were able to dramatically reduce transplant related mortality (<5%) with a very low risk of chronic GVHD. Most relevant to this grant, we also noticed a very low risk of blood cancer relapse in patients who had diseases with a very high risk of recurrence.
We now seek financial support to treat patients in a new trial to confirm that indeed UM171 CB has a potent anti-leukemia effect. For this we propose to recruit 20 very high risk acute leukemia/preleukemia patients (expected cure rate with standard transplant ≈20%) and compare them to historical control patients transplanted with similar high-risk disease. For this, we have brought together a Canadian multidisciplinary team with state-of-the-art expertise in stem cell biology, immunology, bioengineering, cell therapy, statistics and clinical transplantation. Using UM171-expanded CB grafts, we expect a cure rate of at least 50%, more than doubling the current expected results. This could represent a real breakthrough treatment for these mostly uncurable patients.
01/01/2020
31/01/2022
2020
Veronique Moulin (P)
Université Laval
Advancing Clinical Trials
Moulin
Lead
Veronique Moulin
670,645
Self-Assembly Skin Substitutes (SASS) for the treatment of acute wounds of Canadian burn patients
Skin burns
The treatment of burn wounds is based on skin autografts. When the surface that needs to be covered is superior to 50% of the total body surface area, the treatment with autografts becomes strategic, the extent of the burns reducing the donor sites availability. With the tissue engineering method developed in our lab, autologous Self-Assembly Skin Substitutes (SASS) can be produced from only a small skin biopsy and could permanently cover all the patient wounds. Thanks to the Special Access Program of Health Canada, 14 patients have already been treated with very good results. This early phase clinical trial has now been accepted by Health Canada and few patients have been treated in Quebec Province. This project will allow to extend the trial to burn units in the rest of Canada. The aim of this trial is to evaluate this novel therapeutic approach, treating 17 patients to help skin regeneration. We plan to recruit at least 7 patients during the 2 next years and evaluate graft take and the post-grafting scar aspect during 2 to 3 years. Our aim is to treat majority of Canadian patients that have been burned on more than 50% of their body during the 2 years to come. To reach this goal, we will collaborate with the Canadian surgeons that are dedicated to the burn patient treatment. We speculate that SASS treatment will have economic and social benefits as our preliminary results have demonstrated that treatment decreases the morbidity generated by the standard treatment (decreasing further surgery needs and pain of the patients) and improves the quality of the post-burn scars.
Our interdisciplinary team is composed of four internationally known researchers in regenerative medicine from two universities and of plastic surgeons working in the major Canadian burn unit sites. Manufacturing SASS in Tissue processing centre built and directed by our team, we are the only Canadian team dedicated to the reconstruction of organized tissues to treat patients. At the end of the clinical trial and acceptance by Health Canada, we will be the first place in Canada to routinely treat patients with autologous reconstructed skin.
01/01/2020
31/01/2022
2020
Bernard Thébaud (P)
Ottawa Hospital Research Institute
Advancing Clinical Trials
Thébaud
Lead
Bernard Thébaud
638,150
HULC-I: Helping Underdeveloped Lungs with mesenchymal stromal Cells – A phase I trial
Lung
Extreme prematurity is the main cause of death in children below 5 years of age. The most severe complication is bronchopulmonary dysplasia (BPD), a chronic lung disease that follows ventilator and oxygen treatment for acute failure to breathe. BPD also leads to brain damage and blindness. Currently, there is no treatment for BPD. Because these injuries occur in developing organs, consequences are life-long and carry a high economic burden. Thus, effective interventions at this stage of life provide exceptional value.
Our group was the first to demonstrate that umbilical cord-derived mesenchymal stromal cells (uc-MSCs) repair neonatal lung injury in experimental models. We then pioneered several innovations enabling this world’s first clinical trial: (1) a highly efficient, high yield, low passage, GMP clinical-grade uc-MSC product; (2) a novel team science approach (INCuBATOR: Innovative-Neonatal-CellUlar-therapies-for-BPD-Accelerating-Translation-Of-Research) to enhance clinical translation success through rigorous, evidence-based processes mitigating the potential high-risk nature of cell therapy in newborns. Thus, we created a strong, multidisciplinary, well-attuned, international team with complementary expertise to deliver on this research.
HULC-I is a Phase I, dose-escalation trial to determine the safety and feasibility of intravenous injection of allogeneic uc-MSCs for extreme preterm infants at high risk of developing BPD. The study includes an observational control group (n=12) and an interventional group (n=9). Our multi-disciplinary team has extensive experience in stem cell biology/manufacturing, clinical trials, health psychology and economics to ensure the success of this trial. The deliverables are to provide evidence for a larger, Phase II Canadian multi-centre trial, to determine the safety and efficacy of uc-MSCs. Ultimately, HULC-I will provide a potential breakthrough therapy to improve the outcome of extreme preterm babies in Canada and world-wide.
HULC-I will also deliver social and economic benefits by providing a new workforce of HQP and developing novel commercial entities. Our partner at the Technische Universität Dresden holds a patent for the uc-MSC product that is currently being internationalized in Europe, USA and Canada. The spin-off MDTB Cells GmbH will further develop and distribute a novel, high quality uc-derived MSC product with plans to establish a spin-off in Canada to facilitate operations in North America.
01/01/2020
31/01/2022
2020
Lucie Germain (P)
Université Laval
Advancing Clinical Trials
Germain
Lead
Lucie Germain
500,000
Cultured epithelial corneal autografts for the treatment of Canadians with limbal stem cell deficiency
Ocular; limbal stem cell deficiency
Limbal stem cell deficiency (LSCD) is a severe disease caused by damage or depletion of stem cells in the corneal limbal region of the eye following trauma or disease. The LOEX/CHU de Québec, a leader in autologous epithelium therapy using cultured stem cells, has performed the first clinical trial in Canada offering cultured epithelial corneal autograft (CECA) as a treatment for the LSCD.
The objective of the present proposal is to develop a multicenter clinical trial (Quebec, Montreal and Toronto) to recruit a greater number of LSCD patients for the collection of safety data on the CECA graft, but with a primary endpoint focused on efficacy. Therefore, we expect to: i) establish and organize new clinical sites, which involves the training of new cornea specialists for CECA grafting, ii) recruit and treat 34 adult patients and 5 minor patients, and iii) educate and advise Canadian ophthalmologists on this new therapeutic alternative now available in Canada.
Following successful clinical testing, this trial will provide clinical proof-of-concept for a safe and effective stem cell-based therapy accessible to Canadian ophthalmologists and their patients for the treatment of LSCD. Without treatment, LSCD results in severe visual impairments which impacts on the quality of life of patients and their families. LSCD is a rare disease that affects patients' ability of the patient to work, drive and conduct their daily activities. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving vision in their affected eye.
Our interdisciplinary team brings together three fundamental investigators, including two experts in tissue-engineering and an expert in ethical/legal issues, three clinician ophtalmologists, one pathologist, many research professionals experienced in the clinical translation of tissue engineering products and a patient representative. The LOEX is equipped with clean rooms and has been producing CECA since 2012. Thus, our research group has the infrastructure, expertise and knowledge to ensure the success of the project.
01/01/2020
31/01/2022
2020
Yun Li (C)
The Hospital for Sick Children
COVID19 Rapid Response Initiative
Muffat
Co-Investigator
Yun Li, Julien Muffat
90,000
Investigating the role of inflammatory responses in neurological effects of COVID-19, using patient-derived stem cell models
COVID-19, Neural
The COVID-19 pandemic, due to the coronavirus SARS-CoV-2, is taking an enormous toll on populations worldwide. The primary presentation is pneumonia, yet the disease clearly affects multiple organs, often culminating in liver and kidney damage. Severity of the disease may often find its roots in an inappropriately intense and prolonged innate immune response, a so-called cytokine storm, driven by innate immune cells (macrophages). Strikingly, many patients report sensory symptoms, such as loss of smell and taste, pains, visual disturbances, and headaches. These indicate that the virus may target the brain. The brain harbors a population of prototypic tissue-resident innate immune cells, the microglia. In the brain, these cells are normally protected from peripheral insults. However, they will respond to inflammatory stimuli that do reach them, and are known to be the target of neuro-invasive viruses. We propose to investigate the neuro-invasive potential of SARS-CoV-2, with an emphasis on the role of resident innate immune cells in mediating the injury. Given the species restriction of SARS-CoV-2, we will work with a set of novel human tissue culture models that we uniquely developed to investigate inflammatory etiologies of neurological diseases. We previously successfully and rapidly deployed similar technologies during the Zika epidemic. We will assess infection parameters and cellular responses in brain cells derived from patient stem cells. Working with brain-resident immune cells will shed light on the interaction of SARS-CoV-2 with similar cellular targets in other organs, such as the lungs. We will study the virus’ ability to enter, replicate, kill the cells or trigger unchecked inflammation. We will dissect the host machinery involved in these responses by identifying protective or damaging mutations, generated using CRISPR technology for every gene in those cells. Our team has the technical know-how and access to all resources needed to deliver rapidly on our plans.
17/04/2020
16/04/2021
2020
Julien Muffat (P)
The Hospital for Sick Children
COVID19 Rapid Response Initiative
Muffat
Lead
Yun Li, Julien Muffat
90,000
Investigating the role of inflammatory responses in neurological effects of COVID-19, using patient-derived stem cell models
COVID-19, Neural
The COVID-19 pandemic, due to the coronavirus SARS-CoV-2, is taking an enormous toll on populations worldwide. The primary presentation is pneumonia, yet the disease clearly affects multiple organs, often culminating in liver and kidney damage. Severity of the disease may often find its roots in an inappropriately intense and prolonged innate immune response, a so-called cytokine storm, driven by innate immune cells (macrophages). Strikingly, many patients report sensory symptoms, such as loss of smell and taste, pains, visual disturbances, and headaches. These indicate that the virus may target the brain. The brain harbors a population of prototypic tissue-resident innate immune cells, the microglia. In the brain, these cells are normally protected from peripheral insults. However, they will respond to inflammatory stimuli that do reach them, and are known to be the target of neuro-invasive viruses. We propose to investigate the neuro-invasive potential of SARS-CoV-2, with an emphasis on the role of resident innate immune cells in mediating the injury. Given the species restriction of SARS-CoV-2, we will work with a set of novel human tissue culture models that we uniquely developed to investigate inflammatory etiologies of neurological diseases. We previously successfully and rapidly deployed similar technologies during the Zika epidemic. We will assess infection parameters and cellular responses in brain cells derived from patient stem cells. Working with brain-resident immune cells will shed light on the interaction of SARS-CoV-2 with similar cellular targets in other organs, such as the lungs. We will study the virus’ ability to enter, replicate, kill the cells or trigger unchecked inflammation. We will dissect the host machinery involved in these responses by identifying protective or damaging mutations, generated using CRISPR technology for every gene in those cells. Our team has the technical know-how and access to all resources needed to deliver rapidly on our plans.
17/04/2020
16/04/2021
2020
Amy Wong (C)
The Hospital for Sick Children
COVID19 Rapid Response Initiative
Stanford
Co-Investigator
William Stanford, Amy Wong
77,120
Identifying and targeting pulmonary and immune mechanisms in COVID-19 using human stem cell derived lineages
COVID-19, Lung, vascular
Understanding why some COVID-19 patients develop acute respiratory distress syndrome (ARDS) that drives morbidity and mortality is unclear but is urgently needed to determine which patients should be treated early and develop therapeutic interventions to save lives. The two known comorbidities – hypertension and diabetes – associated with severe COVID-19 suggests a vascular pathology. In fact, in addition to the respiratory epithelia, the lung vasculature expresses high levels of angiotensin converting enzyme-2 (ACE-2), the receptor that SARS-CoV-2 uses to infect cells. Additionally, it appears from emerging studies that a myeloid-dominant cytokine storm contributes to lung tissue injury in COVID-19 ARDS.
With our partners at BioSymetrics, we will leverage our team’s expertise in lung and stem cell biology, disease modeling, immunology, bioengineering, drug screening and development, and infectious disease to dissect underlying molecular and cellular mechanisms driving disease severity and screen for disease modifying drugs. To maximize translational impact, our team’s unique approach uses human pluripotent stem cells to generate ACE2-expressing respiratory epithelia grown in a tissue-mimetic air liquid interface and vascular cells grown in a lung-mimetic hydrogel to analyze infectivity and cellular and molecular behaviour in response to SARS-CoV-2. Moreover, we will perform single cell RNA-seq analyses and co-culture studies with control and infected peripheral blood derived myeloid cells to model the altered lung epithelia, vascular, and immune responses in COVID-19. These mechanistic studies will be mined to discover putative biomarkers that identify patients likely to require intensive care so that acute care may be started early to prevent the need for intensive care. Finally, using a novel ACE2 activity high content imaging assay, we will implement a Health Canada/FDA approved drug repurposing screen to identify therapeutics to reduce disease severity.
17/04/2020
16/04/2021
2020
William Stanford (P)
Ottawa Hospital Research Institute
COVID19 Rapid Response Initiative
Stanford
Lead
William Stanford, Amy Wong
118,750
Identifying and targeting pulmonary and immune mechanisms in COVID-19 using human stem cell derived lineages
COVID-19, Lung, vascular
Understanding why some COVID-19 patients develop acute respiratory distress syndrome (ARDS) that drives morbidity and mortality is unclear but is urgently needed to determine which patients should be treated early and develop therapeutic interventions to save lives. The two known comorbidities – hypertension and diabetes – associated with severe COVID-19 suggests a vascular pathology. In fact, in addition to the respiratory epithelia, the lung vasculature expresses high levels of angiotensin converting enzyme-2 (ACE-2), the receptor that SARS-CoV-2 uses to infect cells. Additionally, it appears from emerging studies that a myeloid-dominant cytokine storm contributes to lung tissue injury in COVID-19 ARDS.
With our partners at BioSymetrics, we will leverage our team’s expertise in lung and stem cell biology, disease modeling, immunology, bioengineering, drug screening and development, and infectious disease to dissect underlying molecular and cellular mechanisms driving disease severity and screen for disease modifying drugs. To maximize translational impact, our team’s unique approach uses human pluripotent stem cells to generate ACE2-expressing respiratory epithelia grown in a tissue-mimetic air liquid interface and vascular cells grown in a lung-mimetic hydrogel to analyze infectivity and cellular and molecular behaviour in response to SARS-CoV-2. Moreover, we will perform single cell RNA-seq analyses and co-culture studies with control and infected peripheral blood derived myeloid cells to model the altered lung epithelia, vascular, and immune responses in COVID-19. These mechanistic studies will be mined to discover putative biomarkers that identify patients likely to require intensive care so that acute care may be started early to prevent the need for intensive care. Finally, using a novel ACE2 activity high content imaging assay, we will implement a Health Canada/FDA approved drug repurposing screen to identify therapeutics to reduce disease severity.
17/04/2020
16/04/2021
2020
Duncan Stewart (P)
Ottawa Hospital Research Institute
COVID19 Rapid Response Initiative
Stewart
Lead
Duncan Stewart
300,000
Cellular Immuno-Therapy for COVID-19 induced Acute Respiratory Distress Syndrome: the CIRCA-19 Trial
COVID-19, MSC clinical trial
The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although 80% of infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). This often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world’s first clinical trial using MSC therapy for patients with severe infections (sepsis) which often are associated with ARDS. This trial demonstrated tolerability, and some signs of efficacy. In addition, we have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in 3 different clinical studies. Here, we propose a series of trials to allow us to rapidly initiate a clinical study to establish feasibility and safety of MSCs treatment in patients with COVID-19 related ARDS. In total, 27 patients will be entered into three sequential trial. The first trial, called the ‘Vanguard’ study, is designed to determine the optimal of dose of bone marrow-derived MSCs to be used for these very sick patients. The next two trials will use this same optimal dose of cells, but will administer MSCs derived from the umbilical cord, which is an abundant and readily available source. In this way we will confirm the safety of the use of umbilical cord MSCs and obtain preliminary information about their potential benefits in the treatment of this often lethal disease.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy
Muscle
Rare disease status
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke.
01/01/2020
31/01/2022
2020
Jodi Warman (C)
University of Ottawa
Innovation Research Program for Early Career Investigators
Khacho
Co-Investigator
Mireille Khacho, Jodi Warman
20,300
Mitochondrial dynamics as a therapeutic target for muscle stem cells in muscle wasting diseases
Muscle
Rare disease status
An estimated 4 million Canadians currently suffer from muscle wasting conditions, manifesting as loss of muscle mass and function. Muscle wasting is the most significant cause of disability in the aging population and individuals with muscle degenerative diseases, including muscular dystrophies, myopathies and aging. The decline in muscle function affects mobility, voluntary function and quality of life, often leading to institutionalization and mortality. This imposes a dramatic burden on individuals and society, costing Canadians several billions of dollars per year. Thus, there is a pressing need for the development of preventative and therapeutic strategies targeting muscle wasting. For many years, muscle wasting was thought to be only a problem of the myofibers, yet recent evidence shows that muscle stem cell (MuSC) dysfunction plays a significant role. Adult skeletal muscle normally has a high regenerative capacity, however, within the context of muscle wasting MuSCs are depleted and muscle regeneration is impaired. Currently, the reason for MuSC depletion is unclear and thus there are no therapies targeting their restoration. Understanding the underlying etiological factors leading to MuSC depletion is instrumental in identifying novel approaches to restore muscle repair and function. Our recent studies were the first to uncovered that dysregulation of mitochondrial dynamics and function, as observed in muscle wasting, impairs stem cell longevity and regenerative capacity. The overarching goal of this proposal is to restore MuSC number and function and promote muscle repair in aging and muscle wasting diseases. The combination of our proposed animal and human studies of muscle stem cells will provide novel therapeutic options using pharmaceutical and supplementation strategies. Importantly, this could have immediate translational potential to a clinical environment to improve muscle function and quality of life in patients.
01/09/2020
28/02/2022
2020
Mireille Khacho (P)
University of Ottawa
Innovation Research Program for Early Career Investigators
Khacho
Lead
Mireille Khacho, Jodi Warman
129,700
Mitochondrial dynamics as a therapeutic target for muscle stem cells in muscle wasting diseases
Muscle; various
Rare disease status
An estimated 4 million Canadians currently suffer from muscle wasting conditions, manifesting as loss of muscle mass and function. Muscle wasting is the most significant cause of disability in the aging population and individuals with muscle degenerative diseases, including muscular dystrophies, myopathies and aging. The decline in muscle function affects mobility, voluntary function and quality of life, often leading to institutionalization and mortality. This imposes a dramatic burden on individuals and society, costing Canadians several billions of dollars per year. Thus, there is a pressing need for the development of preventative and therapeutic strategies targeting muscle wasting. For many years, muscle wasting was thought to be only a problem of the myofibers, yet recent evidence shows that muscle stem cell (MuSC) dysfunction plays a significant role. Adult skeletal muscle normally has a high regenerative capacity, however, within the context of muscle wasting MuSCs are depleted and muscle regeneration is impaired. Currently, the reason for MuSC depletion is unclear and thus there are no therapies targeting their restoration. Understanding the underlying etiological factors leading to MuSC depletion is instrumental in identifying novel approaches to restore muscle repair and function. Our recent studies were the first to uncovered that dysregulation of mitochondrial dynamics and function, as observed in muscle wasting, impairs stem cell longevity and regenerative capacity. The overarching goal of this proposal is to restore MuSC number and function and promote muscle repair in aging and muscle wasting diseases. The combination of our proposed animal and human studies of muscle stem cells will provide novel therapeutic options using pharmaceutical and supplementation strategies. Importantly, this could have immediate translational potential to a clinical environment to improve muscle function and quality of life in patients.
01/09/2020
28/02/2022
2020
Yun Li (P)
The Hospital for Sick Children
Innovation Research Program for Early Career Investigators
Li
Lead
Yun Li
150,000
Engineering an organoid model of the hippocampal neurogenic niche for basic and translational research
Neural
The hippocampus is a unique structure in the human brain that contains a long-lasting neurogenic niche. During fetal development, neurons are generated by radial glia (RG), the bona fide neural stem cells of the brain. While RG in most other regions of the human brain are depleted prior to birth, some RG in the fetal hippocampus remain undifferentiated and persist for decades after birth. As a result, the hippocampus is one of the only regions of the brain where new neurons are born throughout life. However, our knowledge of the fetal hippocampal neurogenic niche is extremely limited, because of the inaccessible nature of the human fetal brain. It has been hypothesized that the long-lasting nature of the hippocampal RG critically depends on their ability to enter quiescence. Disruption of this process during fetal development likely has profound consequences on the capacity of postnatal and adult hippocampal neurogenesis. Addressing these important unknowns requires experimental models of the developing human brain, and genetic tools to manipulate the human genome, prerequisites unattainable until recently.
In the current proposal, we seek to engineer a novel organoid model of the human hippocampal neurogenic niche, to study normal and pathological development. Combining breakthrough technologies in human pluripotent stem cells (hPSCs), genome editing, and 3D organoids, my lab has recently reported that human brain development and diseases could be modeled in vitro. In unpublished results, we have created a suite of genetically engineered hPSCs to label, manipulate, and ablate hippocampal RG. These expertise and genetic tools put us at a uniquely advantageous position to carry out the proposed research. Our work will establish a significant long-term resource for studying human hippocampal neurogenesis in health and disease.
01/09/2020
28/02/2022
2020
Stephanie Protze (P)
University Health Network
Innovation Research Program for Early Career Investigators
Protze
Lead
Stephanie Protze, Zachary Laksman
127,400
Developing stem cell-based biological pacemakers for patients with sick sinus syndrome
Cardiac; sick sinus syndrome
Rare disease status
The human heartbeat is controlled by the primary pacemaker known as the sinoatrial node (SAN). Failure of the SAN, due to diseases or aging, causes a life-threatening slow heartbeat and needs to be treated by implantation of an electronic pacemaker. Approximately 21,000 Canadians receive an electronic pacemaker every year, a number that is steadily increasing with an aging population. The treatment with electronic pacemakers has a couple of disadvantages such as the need for surgical battery replacements, the lack of autonomic responsiveness, and the risk of complications such as infection of the leads and pacing-induced heart failure.
In this project we aim to develop a stem cell-derived biological pacemaker that could overcome these disadvantages by replacing the damaged SAN with new functional pacemaker cells. We have already established a method for the generation of stem cell-derived SAN pacemaker cells. A large number of these SAN cells are required to create a biological pacemaker. This can be easiest accomplished by a positive selection process. As part of this project we will validate a novel cell surface marker that we have recently discovered to be present on SAN pacemaker cells. We will test the utility of this marker to isolate large numbers of SAN pacemaker cells from differentiated stem cell cultures. In addition, we will establish a novel animal model of SAN disease and provide proof of concept that these stem cell-derived SAN pacemaker cells can function as a biological pacemaker in this model.
To successfully carry out this translational project, we have put together an interdisciplinary team including: Dr. Laksman (UBC, Vancouver), a clinician scientist; Dr. Laflamme (UHN, Toronto), an expert in cell therapies for the heart; Dr. Bader (UofT, Toronto), a computational biologist; and Dr. Efimov (GWU, Washington, US), a pioneer of experimental electrophysiology with extensive expertise in heart rhythm disorders; and myself, Dr. Protze (UHN, Toronto), an early career investigator with expertise in developmental and stem cell biology.
Taken together, our team will advance the development of biological pacemakers that represent a possible cure, rather than a treatment, for patients with pacemaker diseases in Canada and worldwide.
01/09/2020
28/02/2022
2020
Zachary Laksman (C)
University of British Columbia
Innovation Research Program for Early Career Investigators
Protze
Co-Investigator
Stephanie Protze, Zachary Laksman
22,600
Developing stem cell-based biological pacemakers for patients with sick sinus syndrome
Cardiac
Rare disease status
The human heartbeat is controlled by the primary pacemaker known as the sinoatrial node (SAN). Failure of the SAN, due to diseases or aging, causes a life-threatening slow heartbeat and needs to be treated by implantation of an electronic pacemaker. Approximately 21,000 Canadians receive an electronic pacemaker every year, a number that is steadily increasing with an aging population. The treatment with electronic pacemakers has a couple of disadvantages such as the need for surgical battery replacements, the lack of autonomic responsiveness, and the risk of complications such as infection of the leads and pacing-induced heart failure.
In this project we aim to develop a stem cell-derived biological pacemaker that could overcome these disadvantages by replacing the damaged SAN with new functional pacemaker cells. We have already established a method for the generation of stem cell-derived SAN pacemaker cells. A large number of these SAN cells are required to create a biological pacemaker. This can be easiest accomplished by a positive selection process. As part of this project we will validate a novel cell surface marker that we have recently discovered to be present on SAN pacemaker cells. We will test the utility of this marker to isolate large numbers of SAN pacemaker cells from differentiated stem cell cultures. In addition, we will establish a novel animal model of SAN disease and provide proof of concept that these stem cell-derived SAN pacemaker cells can function as a biological pacemaker in this model.
To successfully carry out this translational project, we have put together an interdisciplinary team including: Dr. Laksman (UBC, Vancouver), a clinician scientist; Dr. Laflamme (UHN, Toronto), an expert in cell therapies for the heart; Dr. Bader (UofT, Toronto), a computational biologist; and Dr. Efimov (GWU, Washington, US), a pioneer of experimental electrophysiology with extensive expertise in heart rhythm disorders; and myself, Dr. Protze (UHN, Toronto), an early career investigator with expertise in developmental and stem cell biology.
Taken together, our team will advance the development of biological pacemakers that represent a possible cure, rather than a treatment, for patients with pacemaker diseases in Canada and worldwide.
01/09/2020
28/02/2022
2020
Jo Stratton (P)
McGill University
Innovation Research Program for Early Career Investigators
Stratton
Lead
Jo Stratton
150,000
Human iPSC ependymal cells: An innovative model to study human brain in health and disease
Neural
The major technological breakthrough of the description of “Yamanaka factors” enables the reprogramming of human cells into pluripotent stem cells appropriate for deriving a diversity of human cells that have previously been inaccessible for study. This includes the study of brain cells, such as neurons and several glia cell types, that are notoriously difficult to access. The ependymal cell – the brain’s epithelial barrier cell, lines the entire ventricular system and is critically understudied largely due to a lack of reliable cellular models for their study. Ependymal cells regulate cerebrospinal fluid (CSF) circulation; and over the last decade, their role in the maintenance of CSF homeostasis is becoming much more appreciated. There is an overwhelming number of neurological conditions and diseases that are subject to ependymal cell abnormalities, which can subsequently interfere with developmental processes, regenerative mechanisms and contribute to disease progression.
Developing a robust method for generating ependymal cell cultures would not only greatly benefit my research program but would also have a wider impact on the research community, given no such method currently exists. Our objective is to use human iPSCs to develop a robust method for the routine culturing of human ependymal cells. In the process of developing this translational method, we will gain a greater understanding of the developmental timelines of human ependymal cells and apply this knowledge to better inform their regenerative potential and how they may become compromised in disease. We can use this system to understand how genes and environment interact in diseases impacting ependymal cells or impacted by ependymal cells - an accomplishment in both the fields of stem cell biology and ependymal cell biology. Ultimately, we will generate methodology that will be disseminated openly via Open-Access journals and at conferences. Along with our team of iPSC and glia experts, Drs Thomas Durcan and Luke Healy, as well as ependymal cell biologist, Jo Anne Stratton, we are well positioned to execute this project. Finally, the McGill Regenerative Network is an instrumental partner for this project, where they will support trainee stipend costs and provide network resources.
01/09/2020
28/02/2022
2020
Amy Wong (P)
The Hospital for Sick Children
Innovation Research Program for Early Career Investigators
Wong
Lead
Amy Wong
150,000
Elucidating the role of CFTR in human fetal lung lineage development
Lung
Rare disease status
Cystic Fibrosis (CF) is a common genetic disease which causes difficulties in breathing, recurrent lung infections. Children under the age of 12 are not eligible for current treatments (at a cost of $300,000 CAD/year for a lifetime) aimed at targeting the main CF genetic mutation. This has been a large debate over the past few years with clinicians arguing for the early treatment of CF in children to mitigate the extent of lung damage caused by this progressively fatal disease. However, there has not been useful models to really understand the impact of CFTR functional correction in human fetuses, neonates, or young children, let alone understand the role of CFTR in normal lung development.
In 2012, I developed the first human lung in the petri dish derived solely from pluripotent stem cells. These stem cells when generated from individuals with CF enabled the use of an unlimited source of lung cells to better understand individual CF disease and personalized screens for therapeutic drugs. My lab has since expanded our stem cell-derived lung model repertoire to include fetal, immature and mature lungs derived from induced pluripotent stem cells. We have the unique models to understand how a defect in CFTR expression can impact normal development and long-term lung functions that impact therapy outcomes. We will do so my combining single cell technologies, mathematical modeling, stem cell and primary tissue models to address: 1) the origins and lineage relationship of cells expressing CFTR during development, 2) CFTR expression and function in normal lung development and, 3) the effects of CFTR mutation in lung lineage development. Our overarching goal is to understand the role of CFTR in early lung development and CF pathogenesis. Early treatment of CF lung disease will translate to meaningful therapeutic outcome that improves the health, economic and social welfare of the patient and benefits our Canadian healthcare system.
01/09/2020
28/02/2022
2020
Natasha Chang (P)
McGill University
Innovation Research Program for Early Career Investigators
Chang
Lead
Natasha Chang
150,000
Targeting muscle stem cells to enhance endogenous repair in Duchenne muscular dystrophy
Muscle; Duchenne Muscular Dystrophy
Rare disease status
Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. Recent studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as normal healthy muscle stem cells and their impairment plays a contributing role in disease progression. Current therapeutic strategies for muscular dystrophy do not address the deficiencies in muscle stem cell function. Here, we describe a novel approach to target muscle stem cells to mitigate the disease. We have found that a group of small molecule compounds known to have anti-tumorigenic properties that protect against muscle wasting have the ability to improve muscle differentiation, the process whereby muscle stem cells make mature muscle cells. This study investigates the use of these compounds to boost the regenerative capacity of muscle stem cells. We propose that enhancing muscle repair through the restoration of muscle stem cell function will improve muscle quality and strength in DMD. The findings from these studies will provide proof-of-concept validation to further develop these compounds for clinical use in DMD patients. This project is lead by Dr. Natasha Chang, an Assistant Professor at McGill University who specializes in muscle stem cell biology and muscle stem cell contributions to muscle pathologies. This project is supported by a multi-disciplinary team of investigators including Dr. Jerry Pelletier and Dr. Imed Gallouzi, experts on mRNA translation mechanisms and muscle wasting, as well as Dr. Gerald Pfeffer, who specializes in neuromuscular diseases. Moreover, this project is supported through generous support from McGill University, the McGill Regenerative Medicine Network, Muscular Dystrophy Canada, and Aurora Scientific Inc.
01/09/2020
28/02/2022
2020
Kathleen Hodgkinson (C)
Memorial University of Newfoundland
Innovation Research Program for Early Career Investigators
Esseltine
Co-Investigator
Jessica Esseltine, Kathleen Hodgkinson
20,000
A personalized, translational approach to understanding inherited Arrhythmogenic Right Ventricular Cardiomyopathy in Newfoundland
Cardiac
Rare disease status
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart disease that can cause sudden death as its first symptom. It tragically shortens the lives of healthy young people, with men affected worse than women. 50% of ARVC men will die by age 40, and 80% by 50 (5% and 20% of women).
Genes are messages written in a DNA alphabet that build proteins. Proteins are the building blocks of the cells from which we are all made. A mistake in a gene can disrupt the protein causing serious disease. ARVC in Newfoundland is caused by a DNA spelling mistake in a gene called TMEM43. This mutation was discovered in Newfoundland. Men and women both inherit the TMEM43 gene mutation, and pass it on to 50% of their children. Thus, ARVC is known as “The Newfoundland curse”.
Although all people with the TMEM43 gene mutation will get ARVC, it is not the same severity in everyone. We know nothing about what this gene change does to heart cells. We do not know why women are protected compared to men. We do not know why some dies suddenly or need a heart transplant, while others live relatively normal lives.
We have a dedicated group of families invested in helping with our research. We will collect skin samples from affected and unaffected family members and ‘reprogram’ their skin cells into induced pluripotent stem cells (iPSC). These iPSCs can become any cell type. So we can take skin cells and turn them into beating heart cells. We can then investigate how ARVC heart cells are different than their unaffected siblings. We can “repair” the DNA in these cells using CRISPR-Cas9 technology. The large families mean we can access subjects with severe forms of ARVC, and less severe forms, and access their gene negative brothers and sisters as controls.
Although concentrated within NL, ARVC caused by this mutation is seen worldwide. This research proposal will allow us to understand basic ARVC biology, which may lead to new therapies based on understanding the causes of the variation in disease presentation we see, leading to true precision medicine.
01/09/2020
28/02/2022
2020
Jessica Esseltine (P)
Memorial University of Newfoundland
Innovation Research Program for Early Career Investigators
Esseltine
Lead
Jessica Esseltine, Kathleen Hodgkinson
130,000
A personalized, translational approach to understanding inherited Arrhythmogenic Right Ventricular Cardiomyopathy in Newfoundland
Cardiac; Arrhythmogenic Right Ventricular Cardiomyopathy
Rare disease status
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart disease that can cause sudden death as its first symptom. It tragically shortens the lives of healthy young people, with men affected worse than women. 50% of ARVC men will die by age 40, and 80% by 50 (5% and 20% of women).
Genes are messages written in a DNA alphabet that build proteins. Proteins are the building blocks of the cells from which we are all made. A mistake in a gene can disrupt the protein causing serious disease. ARVC in Newfoundland is caused by a DNA spelling mistake in a gene called TMEM43. This mutation was discovered in Newfoundland. Men and women both inherit the TMEM43 gene mutation, and pass it on to 50% of their children. Thus, ARVC is known as “The Newfoundland curse”.
Although all people with the TMEM43 gene mutation will get ARVC, it is not the same severity in everyone. We know nothing about what this gene change does to heart cells. We do not know why women are protected compared to men. We do not know why some dies suddenly or need a heart transplant, while others live relatively normal lives.
We have a dedicated group of families invested in helping with our research. We will collect skin samples from affected and unaffected family members and ‘reprogram’ their skin cells into induced pluripotent stem cells (iPSC). These iPSCs can become any cell type. So we can take skin cells and turn them into beating heart cells. We can then investigate how ARVC heart cells are different than their unaffected siblings. We can “repair” the DNA in these cells using CRISPR-Cas9 technology. The large families mean we can access subjects with severe forms of ARVC, and less severe forms, and access their gene negative brothers and sisters as controls.
Although concentrated within NL, ARVC caused by this mutation is seen worldwide. This research proposal will allow us to understand basic ARVC biology, which may lead to new therapies based on understanding the causes of the variation in disease presentation we see, leading to true precision medicine.
01/09/2020
28/02/2022
2020
Jean-François Bouchard (C)
Université de Montréal
Fueling Biotechnology Partnerships Awards
Bernier
Co-Investigator
Gilbert Bernier, May Griffith, Jean-François Bouchard
66,000
Photoreceptor transplantation for the treatment of retinal degenerative diseases
Ocular
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level.
01/01/2020
31/01/2022
2020
May Griffith (C)
Université de Montréal
Fueling Biotechnology Partnerships Awards
Bernier
Co-Investigator
Gilbert Bernier, May Griffith, Jean-François Bouchard
66,000
Photoreceptor transplantation for the treatment of retinal degenerative diseases
Ocular
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level.
01/01/2020
31/01/2022
2020
Gilbert Bernier (P)
Hôpital Maisonneuve-Rosemont
Fueling Biotechnology Partnerships Awards
Bernier
Lead
Gilbert Bernier, May Griffith, Jean-François Bouchard
368,000
Photoreceptor transplantation for the treatment of retinal degenerative diseases
Ocular; multiple diseases
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level.
01/01/2020
31/01/2022
2020
Massimiliano Paganelli (P)
CHU Sainte-Justine
Fueling Biotechnology Partnerships Awards
Paganelli
Lead
Massimiliano Paganelli
500,000
iPSC-derived encapsulated liver tissue to treat acute liver failure: pivotal confirmation in large animals
Liver Failure
Liver failure is the common outcome of most progressive liver diseases, affecting millions of people worldwide. Acute liver failure (ALF) is an extremely severe, progressive syndrome resulting from a sudden insult (like a drug, virus or toxin) to a previously healthy liver that affects thousands of people every year. Patients with ALF need to receive a liver transplant within days from the diagnosis, before their disease becomes irreversibly too severe. Over the last 3 years, with the support of the Stem Cell Network and other provincial and federal funding agencies, we developed an implantable product derived from human stem cells capable of treating ALF, avoiding transplantation. We already showed that what we call the Encapsulated Liver Tissue (ELT) is capable to perform mature liver function in a dish. We also showed that the ELT is safe and effective in treating ALF in rodents, without the risk of rejection or tumor formation. The ELT showed a significant competitive edge over similar products that are being developed worldwide. To promote the development and maturation of this technology and ease its translation to the patients, we created a spin-off company (Morphocell Technologies) and licensed our IP. We are already working with this Canadian regenerative medicine company and with the Centre for Commercialization of Regenerative Medicine (CCRM) to transform the ELT into a safe product for human use. With this project, we will collaborate with Morphocell, CCRM and other Canadian leading experts and stakeholders to confirm the safety and efficacy of the ELT in a large animal model of ALF. This will allow moving this promising treatment towards a first clinical trial in patients with ALF. This grant will support Canadian leadership in this field, help the growth of a promising Canadian biotechnology company (contributing to job creation) and foster the creation of unique scientific and technical expertise. If successful, this project will bring closer to the patients what has been widely recognized as a disruptive treatment for liver disease, which could save and improve the quality of life of thousands of patients with ALF and hundreds of thousands with chronic liver failure, worldwide.
01/01/2020
31/01/2022
2020
Corrine Hoesli (C)
McGill University
Fueling Biotechnology Partnerships Awards
Kieffer
Co-Investigator
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli
130,000
A Bioprinted Insulin-Producing Device for Diabetes
Diabetes
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market.
01/01/2020
31/01/2022
2020
Megan Levings (C)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Kieffer
Co-Investigator
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli
90,000
A Bioprinted Insulin-Producing Device for Diabetes
Diabetes
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market.
01/01/2020
31/01/2022
2020
Steven Paraskevas (C)
McGill University
Fueling Biotechnology Partnerships Awards
Kieffer
Co-Investigator
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli
70,000
A Bioprinted Insulin-Producing Device for Diabetes
Diabetes
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market.
01/01/2020
31/01/2022
2020
James Piret (C)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Kieffer
Co-Investigator
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli
80,000
A Bioprinted Insulin-Producing Device for Diabetes
Diabetes
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market.
01/01/2020
31/01/2022
2020
Timothy Kieffer (P)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Kieffer
Lead
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli
130,000
A Bioprinted Insulin-Producing Device for Diabetes
Diabetes
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market.
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP.
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP.
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP.
01/09/2020
28/02/2022
2020
Peter Zandstra (P)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Zandstra
Lead
Peter Zandstra, David Knapp, Robert Holt
266,300
Enabling a platform for customized pluripotent stem cell derived T-cell therapies
Blood, CAR-T
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications.
01/09/2020
28/02/2022
2020
David Knapp (C)
Université de Montréal
Fueling Biotechnology Partnerships Awards
Zandstra
Co-Investigator
Peter Zandstra, David Knapp, Robert Holt
40,000
Enabling a platform for customized pluripotent stem cell derived T-cell therapies
Blood, CAR-T
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications.
01/09/2020
28/02/2022
2020
Robert Holt (C)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Zandstra
Co-Investigator
Peter Zandstra, David Knapp, Robert Holt
43,700
Enabling a platform for customized pluripotent stem cell derived T-cell therapies
Blood, CAR-T
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications.
01/09/2020
28/02/2022
2020
Bartha Knoppers (P)
McGill University
Translation & Society
Knoppers
Lead
Bartha Knoppers
74,836
Ethical and Legal Framework for Direct-to-Participant (DTP) Recruitment
ELSI, patient recruitment
An important impediment to research progress in stem cell research, particularly for rare diseases, is the recruitment of participants for data and sample collection. Addressing this challenge, Canadian researchers are currently exploring the use of international Direct-to-Participant (DTP) recruitment, a novel recruitment strategy harnessing the communication and networking potential of the internet and social media platforms. DTP will impact how research studies are conducted as the model allows the direct recruitment, consenting and enrollment of participants via the internet without involvement from other researchers or institutions/hospitals. Presently, the benefits of DTP recruitment are unknown while little research has been conducted regarding the ethical/legal implications of this methodology. Likewise, there is a lack of national and international guidance for the appropriate and legitimate uses of DTP recruitment, as well as how best to resolve the ethical/legal concerns that can unfold, since many countries – including Canada – have yet to clearly address the issue. The absence of proper governance presents challenges for researchers when navigating the different regulatory and ethical requirements and increases the likelihood of risks to participants.
The main objective of this project is to fill this ethical and policy gap by: i) examining the ethical/legal issues of international DTP recruitment (for adult and minor participants), and ii) yielding concrete, practical ethical guidance and tools for Canadian researchers and REBs. In collaboration with the Program for Individualized Cystic Fibrosis Therapy (CFIT) at SickKids, we will first build a case study to examine the feasibility and utility of international DTP recruitment, while producing practical, context specific governance framework and recruitment tools. Knowledge and pragmatic experience gained from the CFIT case study, along with consultations with national stakeholders (REB representatives, researchers, oversight agencies and policy makers), will contribute to the development of Canadian Best Practice Guidelines for DTP recruitment. As innovative and fundamental resources for Canadian REBs and researchers, the guidelines and practical tools will directly address an immediate need for clear policy and guidance for international DTP recruitment in stem cell research. They will also set the standards for Canada and internationally, consolidating Canada’s position as a leader in policy development.
01/01/2020
31/01/2022
2020
Kelly Cobey (C)
Ottawa Hospital Research Institute
Translation & Society Team Award
Thébaud
Co-Investigator
Bernard Thébaud, Manoj Lalu, Kelly Cobey
15,000
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research
ELSI, MSCs
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman.
01/09/2020
28/02/2022
2020
Manoj Lalu (C)
Ottawa Hospital Research Institute
Translation & Society Team Award
Thébaud
Co-Investigator
Bernard Thébaud, Manoj Lalu, Kelly Cobey
58,500
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research
ELSI, MSCs
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman.
01/09/2020
28/02/2022
2020
Bernard Thébaud (P)
Ottawa Hospital Research Institute
Translation & Society Team Award
Thébaud
Lead
Bernard Thébaud, Manoj Lalu, Kelly Cobey
101,500
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research
ELSI, MSCs
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman.
01/09/2020
28/02/2022
2022
Véronique Moulin (P)
Université Laval
Clinical Trial Awards
Moulin
Lead
Véronique Moulin
581,700
Tissue engineering to treat Canadian burn patients: the Self-Assembled Skin Substitutes (SASS)
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites. With the tissue engineering methods developed in our lab, autologous Self-Assembled Skin Substitutes (SASS) can be produced and could permanently cover all the patient wounds. This early phase clinical trial has now been accepted by Health Canada and 14 patients have been treated. The objective is to complete the clinical trial and apply for Health Canada authorization to offer our product in Canada.
To reach this goal, we will collaborate with surgeons that are dedicated to treating burn patients. We speculate that SASS treatment will have economic and social benefits as our preliminary results demonstrated that treatment decreases morbidity caused by standard treatments and improves the quality of the post-burn scars.
Our team is composed of four internationally known researchers in regenerative medicine from two universities and of plastic surgeons working in major Canadian burn unit sites. Manufacturing SASS in a tissue processing centre built and directed by our team, we are the only Canadian team dedicated to the reconstruction of organized tissues to treat patients. Following acceptance by Health Canada, we will be the first team in Canada to routinely treat patients with autologous reconstructed skin.
01/04/2022
31/01/2025
2022
David Thompson (P)
University of British Columbia
Clinical Trial Awards
Thompson
Lead
David Thompson
1,000,000
Clinical Trial of the First Gene-Edited Cell Replacement Therapy for Type 1 Diabetes
Diabetes is a debilitating disorder of high blood sugar that afflicts millions of Canadians. People living with type 1 diabetes lack the cells that release the hormone insulin, so multiple daily insulin injections remain the conventional way to control blood sugar levels and survive. We and others have demonstrated that transplant of clusters of insulin-producing cells, called islets, can reduce or even eliminate insulin injections. Unfortunately, the only source of islets for transplant is recently deceased donors and only a tiny fraction of those in need can receive them. There have been remarkable breakthroughs in unraveling the process by which islet cells develop naturally in the body. As a result, it is now possible to replicate this process in the lab with cultured stem cells. We have been conducting clinical trials in which islet precursor cells generated from stem cells are loaded into thin devices and implanted under the skin. Our initial assessments are very encouraging, but patients are required to take powerful immunosuppressants. Now in a world’s first we will test cells that have been genetically engineered to be stealthy such that we can achieve our objective of transplanting the cells without the need for immunosuppression. If successful, this innovative approach could provide a cure for diabetes, freeing Canadians from insulin injections, debilitating complications, and the economic burden of this disease.
01/04/2022
31/01/2025
2022
Lauralyn McIntyre (P)
Ottawa Hospital Research Institute
Clinical Trial Awards
McIntyre
Lead
Lauralyn McIntyre
999,850
Umbilical Mesenchymal Stem Cells as Cellular Immunotherapy for Septic Shock (UC-CISS): A Phase II RCT
Severe infection with shock (septic shock) in the intensive care unit (ICU) accounts for approximately 20% of admissions, of which 20 to 40% will die. Septic shock is associated with an uncontrolled inflammatory response that is initiated by an infectious organism. Studies done in septic animals suggest that the infusion of mesenchymal stem cells (MSCs) balance inflammation, help with repair of injured organs, and reduce death. Hence, it represents a promising potential therapy for septic shock._x000D_
We completed the first in the World Phase I safety trial of MSCs (n=9) versus controls (n=21) in 30 patients with septic shock (CISS Phase I trial). The CISS Phase I trial results confirmed the optimum dose and that treatment with MSCs is safe._x000D_
The Phase II trial (UC-CISS II) will determine whether MSCs as compared to placebo reduce organ failures. UC-CISS II will also continue to evaluate safety and determine whether MSCs improve clinical and patient important outcomes. UC-CISS II will randomize 122 ICU patients with septic shock to previously frozen MSCs or placebo across Canadian centers. The frequency of adverse events (AEs) and serious AEs will be recorded. Blood will be drawn for inflammation markers and the effectiveness of MSC therapy as compared to its cost will be evaluated. _x000D_
UC-CISS II results will be used to support an international Phase III MSC trial which if positive could save thousands of lives and restore the function and quality of life of septic shock survivors.
01/04/2022
31/01/2025
2022
Anastasia Tikhonova (P)
University Health Network
Early Career Researcher Jump Start Awards
Tikhonova
Lead
Anastasia Tikhonova, Courtney Jones
255,750
Targeting the bone marrow microenvironment to promote hematopoietic regeneration
Cancer
Bone marrow niche, hematopoiesis, hematopoietic regeneration, bone marrow microenvironment, hematopoietic stem cell transplantation, metabolism
Patients with cancers are often treated with multiple rounds of chemotherapy. Many patients receiving chemotherapy also develop long-term bone injury and have compromised blood cell development. Blood stem cells are maintained by specialized “support cells” in the bone marrow. Dysfunction of bone marrow support cells has been linked to bone marrow transplant failure. However, what causes this dysfunction and whether it can be reversed to improve transplantation is not known. Using state-of-the-art techniques, we will study the impact of different chemotherapy agents on blood stem cells and their surrounding ecosystem. Our ultimate goal is to define the optimal bone marrow conditions, to improve the quality of life of cancer survivors.
01/04/2022
31/01/2025
2022
Courtney Jones (C)
University Health Network
Early Career Researcher Jump Start Awards
Tikhonova
Co-Investigator
Anastasia Tikhonova, Courtney Jones
44,250
Targeting the bone marrow microenvironment to promote hematopoietic regeneration
Cancer
Bone marrow niche, hematopoiesis, hematopoietic regeneration, bone marrow microenvironment, hematopoietic stem cell transplantation, metabolism
Patients with cancers are often treated with multiple rounds of chemotherapy. Many patients receiving chemotherapy also develop long-term bone injury and have compromised blood cell development. Blood stem cells are maintained by specialized “support cells” in the bone marrow. Dysfunction of bone marrow support cells has been linked to bone marrow transplant failure. However, what causes this dysfunction and whether it can be reversed to improve transplantation is not known. Using state-of-the-art techniques, we will study the impact of different chemotherapy agents on blood stem cells and their surrounding ecosystem. Our ultimate goal is to define the optimal bone marrow conditions, to improve the quality of life of cancer survivors.
01/04/2022
31/01/2025
2022
Mamatha Bhat (P)
University Health Network
Early Career Researcher Jump Start Awards
Bhat
Lead
Mamatha Bhat
300,000
A Nanoparticle-based Strategy to Therapeutically Restore Regenerative Capacity in Cirrhotic Livers
The liver is the only internal organ in the body that can quickly regenerate. One in four Canadians is affected by liver disease. Liver disease is often silent and scars the liver, causing cirrhosis over many years, which reduces its ability to regenerate. Almost a third of these people will die or become ineligible for a liver transplant. To help patients with end-stage liver disease, we need to understand what makes the liver regenerate and harness this as a therapeutic strategy. _x000D_
_x000D_
We know that one of the signaling pathways, called the Hippo-YAP, controls tissue regeneration. When we remove part of the liver in mice, rapid liver regeneration increases the number of YAP-dependent genes, which are reduced in presence of fibrosis. However, fibrotic livers that regenerate are able to rescue the liver from worsening scarring. To better understand the mechanisms driving liver regeneration despite scarring, we will use single-cell profiling technology to identify genes in livers that retain the capacity to regenerate. We will then examine a liver-selective lipid-based particles strategy to see if it can help improve regeneration even when the liver is scarred, while sparing the rest of body any side effects. _x000D_
_x000D_
This project will provide the first steps towards a unique therapeutic strategy to rescue defective liver regeneration in patients with chronic liver disease and help them live longer._x000D_
_x000D_
01/04/2022
31/01/2025
2022
Sheila Teves (P)
University of British Columbia
Early Career Researcher Jump Start Awards
Teves
Lead
Sheila Teves
300,000
Transcription regulation of hiPSC-derived cardiomyocytes during maturation and hypertrophic cardiomyopathy
Heart disease is the leading cause of death worldwide, with almost 9 million deaths globally in 2019 alone. In the US, 1 in every 4 deaths is due to heart failure, with estimated costs to the US economy at about $219 billion each year. More importantly, as the population on average is living longer, heart disease is on the rise. Therefore, demand for better interventions and treatments will increase over time._x000D_
One challenge with developing new therapeutics for heart disease is that most of the research uses animal models that do not necessarily mimic human disease. Over the last two decades, scientists have discovered a way to convert adult human cells into a more stem cell-like state. These so-called induced pluripotent stem cells can then be differentiated into heart cells like cardiomyocytes. These patient derived cells provide a promising new system for heart disease drug screening, except that they fail to fully mature and instead resemble the immature cells seen in the inherited heart disease called hypertrophic cardiomyopathy. Therefore, the main goal of this proposed project is to discover the determining factors that allow for cardiomyocytes from human induced pluripotent stem cells to fully mature. We will use gene editing, genomics, and proteomics to learn how gene expression changes between immature and mature cardiomyocytes, and apply this knowledge towards identifying new targets for therapeutic intervention, specifically for hypertrophic cardiomyopathy. _x000D_
01/04/2022
31/01/2025
2022
Amy Wong (P)
The Hospital for Sick Children
Early Career Researcher Jump Start Awards
Wong
Lead
Amy Wong, Bo Wang, Nika Shakiba
135,272
Deciphering cell competition during iPSC differentiation towards lung epithelia
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases.
01/04/2022
31/01/2025
2022
Bo Wang (C)
University Health Network
Early Career Researcher Jump Start Awards
Wong
Co-Investigator
Amy Wong, Bo Wang, Nika Shakiba
44,625
Deciphering cell competition during iPSC differentiation towards lung epithelia
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases.
01/04/2022
31/01/2025
2022
Nika Shakiba (C)
University of British Columbia
Early Career Researcher Jump Start Awards
Wong
Co-Investigator
Amy Wong, Bo Wang, Nika Shakiba
120,103
Deciphering cell competition during iPSC differentiation towards lung epithelia
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases.
Duchenne muscular dystrophy (DMD) is a severely debilitating and fatal paediatric muscle disease that affects 1 in every 5,000 Canadian male births. With the help of corticosteroids, cardiac and respiratory medical care, DMD patients can now live up to 30 years of age. However, despite intense research efforts to understand the cause and progression of the disease, there still remains no effective cure for DMD. Historically, DMD has been viewed as a disease affecting the integrity of the muscle tissue, which leads to repetitive weakening and damage of the muscle fibers. However, new studies have shown that muscle stem cells, which are stem cells that reside within the muscle, are also affected in DMD. DMD stem cells do not function as normal healthy muscle stem cells, and their dysfunction plays a role in disease progression. Moreover, current DMD therapeutic strategies do not target muscle stem cells. Our research program aims to characterize muscle stem cells in DMD and to understand how they are dysfunctional. We have found that a metabolic nutrient recycling pathway is altered in DMD muscle stem cells. Our study aims to identify strategies to restore muscle stem cell function to ameliorate muscle degenerative disease. The findings from this research program will provide a proof-of-concept for targeting muscle stem cells to restore stem cell function as a therapeutic strategy for patients with DMD.
01/04/2022
31/01/2025
2022
Nika Shakiba (P)
University of British Columbia
Early Career Researcher Jump Start Awards
Shakiba
Lead
Nika Shakiba
300,000
Elucidating the competitive advantage of aberrant pluripotent stem cells in suspension bioprocesses
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to understand how variants survive and thrive in culture. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at the growth of each cell. Using computational models, we will untangle these complex datasets and determine whether variants bully normal cells, using cell killing to take over the culture._x000D_
_x000D_
Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world leader in cell therapy manufacturing for regenerative medicine.
01/04/2022
31/01/2025
2022
Julien Muffat (P)
The Hospital for Sick Children
Early Career Researcher Jump Start Awards
Muffat
Lead
Julien Muffat
300,000
Engineering microglia to support oligodendrocyte transplants, and improve remyelination after white matter injury
The human brain has very limited capacity for regeneration, as seen in the progressive decline in Multiple Sclerosis One of the components destroyed in MS is the sheath that insulates the electrical wires within the brain and spinal cord. When the sheaths are gone, the wires die. The cells that form the wires cannot regenerate, but the sheaths can be repaired. If they are repaired early enough during MS, the electrical wiring will also survive, and the patient will improve. There is a population of brain immune cells, maintaining the integrity of the sheath. With age, immune cells and sheath cells lose their regenerative abilities. We can rejuvenate skin cells into stem cells, and turn them into electrical nerve cells, sheath cells, and brain immune cells. We can make a model of the electrical wiring of the brain in a culture dish. This teaches us things that animal models cannot. With this model, we will study how sheath cells contact the nerve cells, and whether the presence of immune cells helps. Later, we will induce the death of sheath cells, and observe tissue responses, mimicking aspects of MS. We will then add rejuvenated sheath cells and immune cells, to test whether either or both can restore tissue integrity and function. If, as we predict, immune cells can help sheath cells restore nerve integrity, this will pave the way for rapid application to patients, finding drugs that further improve this process, or using the patient’s own cells to restore function
01/04/2022
31/01/2025
2022
Ly Vu (P)
University of British Columbia
Early Career Researcher Jump Start Awards
Vu
Lead
Ly Vu
300,000
Modulating activity of RNA regulating proteins to preserve long-term regenerative potential of Hematopoietic Stem Cells
The focus of this proposed project is umbilical cord blood-derived hematopoietic stem cells (CB-HSCs) ex vivo expansion. CB-HSCs have long been considered a key source of stem cell therapy for hematological disorders. However, the inadequate cell dose isolated from a single cord blood unit still represents a major challenge in the field. While expansion of HSCs ex vivo offers a technical solution to the limited number of cells, increasing evidence points to the reduced long-term engraftment of cultured HSCs when comparing to unexpanded HSCs. Therefore, overcoming the diminished potency of expanded HSCs is essential to push the field forward and enable the wider use of CB-HSCs in regenerative medicine. In this proposal, we aim to uncover new mediators and molecular networks controlling HSCs function under the ex vivo culture conditions. The overarching goal is to leverage the gained knowledge to implement innovative approaches to improve HSCs expansion by preserving their self-renewal capacity. In addition, mechanistic insights into the ability of HSCs to mitigate stresses and maintain their life-long repopulation capacity will enhance our understanding of stem cell biology, thus have implications in the broader stem cell research and regenerative medicine field.
01/04/2022
31/01/2025
2022
Daniel Coutu (P)
Ottawa Hospital Research Institute
Early Career Researcher Jump Start Awards
Coutu
Lead
Daniel Coutu
300,000
Pharmacological rejuvenation of skeletal stem cells for use in regenerative orthopedic surgery
Chronic and debilitating conditions affecting the joints or skeleton affect over half of the Canadian population. These can be caused by trauma, normal degeneration, wear and tear, chronic inflammation or congenital malformations. The skeleton is composed of a variety of tissues including bone, cartilage, tendons, and ligaments. While it is widely assumed that stem cells are responsible for the growth, maintenance and repair of these tissues, these stem cells remain poorly characterized to date and most skeletal tissues lose regenerative capacity with age or repeated trauma. For this reason, there is an incentive to better study stem cells of the skeletal system and develop better regenerative therapies for patients. The project we propose here will study the properties of newly identified skeletal stem cell populations for their capacity to enhance skeletal tissue regeneration. We will use high-end genomics and imaging methods to study skeletal stem cells from both mouse and human tissues. We will screen pharmacological compounds for their capacity to improve tissue regeneration by stem cells using animal models of acute injury and chronic osteoarthritis. The project we propose will highlight the properties of skeletal stem cells and will be a key stepping-stone to develop and bring new therapies to patients suffering chronic, painful and debilitating orthopedic conditions.
01/04/2022
31/01/2025
2022
Carl de Boer (P)
University of British Columbia
Early Career Researcher Jump Start Awards
Boer
Lead
Carl de Boer
300,000
Decoding human cis-regulatory logic in development to treat disease
Many common diseases, including heart disease, are thought to be caused in part by genetics. Each individual has a unique genetic makeup, which affects their disease risk in ways we do not completely understand. However, we do know that disease-associated genetic variation often lies in the DNA sequences that control when and where genes are activated. This variation causes disease by turning the genes on or off at the wrong time or in the wrong cell. Our limited understanding of the code that cells use to interpret the DNA restricts our ability to predict how genetic variation alters gene activity. Our work aims to learn this code. We will create gene regulation computer models using data from experimental measurements of synthetic DNA sequences. Our innovation lies in enabling many more sequences (tens of millions) to be measured at once, providing enough data to learn complex computer models. We are interested in heart development, and will study the cells that cause the heart to beat (cardiomyocytes) and their precursors (pluripotent cells). Once we have learned the gene regulatory code, we will use it to determine how genetics alters disease risk. Next, we will use our models to design DNA sequences that activate genes only in specific cell types that may be useful in gene therapies. This work will improve our ability to identify people at a risk of developing disease, and will enable the development of therapeutics that treat disease.
01/04/2022
31/01/2025
2022
Maryam Faiz (P)
University of Toronto
Early Career Researcher Jump Start Awards
Faiz
Lead
Maryam Faiz, Scott Yuzwa, Samer Hussein
154,500
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease.
01/04/2022
31/01/2025
2022
Scott Yuzwa (C)
University of Toronto
Early Career Researcher Jump Start Awards
Faiz
Co-Investigator
Maryam Faiz, Scott Yuzwa, Samer Hussein
50,500
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease.
01/04/2022
31/01/2025
2022
Samer Hussein (C)
University of Toronto
Early Career Researcher Jump Start Awards
Faiz
Co-Investigator
Maryam Faiz, Scott Yuzwa, Samer Hussein
95,000
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease.
01/04/2022
31/01/2025
2022
Samantha Payne (P)
University of Guelph
Early Career Researcher Jump Start Awards
Payne
Lead
Samantha Payne
273,775
Investigating neuron-dependent cues to promote tissue regeneration
A common response to organ or tissue damage is scarring. Aside from cosmetic considerations, scarring in organs such as the liver or lungs can lead to impaired function, disability, and reduced quality of life. Following tissue damage, scarring is caused by the abnormal activity of cells called fibroblasts, which create protein-rich stiffened matrix. In non-mammalian species, in place of scarring there is complete regeneration and restoration of function. Understanding why the response to injury differs between species will help to generate therapeutics to promote regeneration over scarring. Virtually every tissue of the body contains nerves which connect peripheral organs and tissues to the brain. In select conditions nerves can promote regeneration, but it not clearly understood how. The objective of this research project is to study the role of nerves in modulating the response to injury to develop new therapeutics to promote regeneration over scarring. We will investigate the effect of nerves on scar-forming cells to gain an understanding of why humans and other mammals form scars while non-mammals do not. This project is innovative because it will use something already present in the injury environment – nerves – and harness them towards therapeutics. Understanding how nerves prevent scar formation will help to develop treatments that will improve patient quality of life and have economic benefits to Canada in terms of lowering long-term disability costs.
01/04/2022
31/01/2025
2022
Shinichiro Ogawa (P)
University Health Network
Fueling Biotechnology Partnerships Awards
Ogawa
Lead
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland
331,500
Developing functional 3D bioprinted liver tissues with sustained immune evasion
Liver Disease
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_
01/04/2022
31/03/2024
2022
Gordon Keller (C)
University Health Network
Fueling Biotechnology Partnerships Awards
Ogawa
Co-Investigator
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland
5,000
Developing functional 3D bioprinted liver tissues with sustained immune evasion
Liver Disease
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_
01/04/2022
31/03/2024
2022
Ian McGilvray (C)
University Health Network
Fueling Biotechnology Partnerships Awards
Ogawa
Co-Investigator
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland
23,750
Developing functional 3D bioprinted liver tissues with sustained immune evasion
Liver Disease
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_
01/04/2022
31/03/2024
2022
Sonya MacParland (C)
University Health Network
Fueling Biotechnology Partnerships Awards
Ogawa
Co-Investigator
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland
39,750
Developing functional 3D bioprinted liver tissues with sustained immune evasion
Liver Disease
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_
01/04/2022
31/03/2024
2022
Michael Underhill (P)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Underhill
Lead
Michael Underhill, Pamela Hoodless
324,200
Novel therapeutic strategies to promote liver regeneration
Mesenchymal progenitors (MPs) are a type of stem/progenitor cell, present in all tissues of our bodies. Normally, these cells are in a quiet (i.e., quiescent) state. Quiescence is an important property of many progenitors, and is critical to the healthy maintenance, renewal and regeneration of tissues. MPs exit quiescence and become activated following injury, inflammation and disease. Activated MPs have critical and diverse roles in supporting regeneration, and directly contribute to the healed tissue. Following successful regeneration, a subset of activated cells returns to a quiescent state. In other instances, activated MPs endure, contribute to tissue repair and cause fibrosis, which is associated with the accumulation of scar tissue that typically impairs organ function. Fibrosis underlies ~45% of chronic disease. Globally, chronic liver disease is a major health burden, afflicting ~844 million people. Currently, the only therapeutic option is liver transplantation, and with the shortage of livers available, there is a high unmet need for anti-fibrotic therapies. A novel genetic model will be used to explore the contribution of MPs to fibrosis, with an emphasis on the development of therapeutic approaches that enhance MP quiescence and thereby reduce fibrosis. These studies are expected to generate intellectual property and critical efficacy data, enabling the advancement of this program into the clinic to positively affect the lives of millions of patients worldwide.
01/04/2022
31/03/2024
2022
Pamela Hoodless (C)
BC Cancer, part of the Provincial Health Services Authority
Fueling Biotechnology Partnerships Awards
Underhill
Co-Investigator
Michael Underhill, Pamela Hoodless
75,000
Novel therapeutic strategies to promote liver regeneration
Mesenchymal progenitors (MPs) are a type of stem/progenitor cell, present in all tissues of our bodies. Normally, these cells are in a quiet (i.e., quiescent) state. Quiescence is an important property of many progenitors, and is critical to the healthy maintenance, renewal and regeneration of tissues. MPs exit quiescence and become activated following injury, inflammation and disease. Activated MPs have critical and diverse roles in supporting regeneration, and directly contribute to the healed tissue. Following successful regeneration, a subset of activated cells returns to a quiescent state. In other instances, activated MPs endure, contribute to tissue repair and cause fibrosis, which is associated with the accumulation of scar tissue that typically impairs organ function. Fibrosis underlies ~45% of chronic disease. Globally, chronic liver disease is a major health burden, afflicting ~844 million people. Currently, the only therapeutic option is liver transplantation, and with the shortage of livers available, there is a high unmet need for anti-fibrotic therapies. A novel genetic model will be used to explore the contribution of MPs to fibrosis, with an emphasis on the development of therapeutic approaches that enhance MP quiescence and thereby reduce fibrosis. These studies are expected to generate intellectual property and critical efficacy data, enabling the advancement of this program into the clinic to positively affect the lives of millions of patients worldwide.
01/04/2022
31/03/2024
2022
Guy Sauvageau (P)
Université de Montréal
Horizon Awards
Sauvageau
Lead
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
1,282,964
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Etienne Gagnon (C)
Université de Montréal
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
625,110
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Josée Hébert (C)
Hôpital Maisoneuve-Rosemont, centre de recherche
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
140,000
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Ma'n Zawati (C)
McGill University
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
124,926
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Peter Zandstra (C)
University of British Columbia
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
157,500
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Nika Shakiba (C)
University of British Columbia
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
75,000
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Philippe Roux (C)
Université de Montréal
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
117,500
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
Vincent-Philippe Lavallée (C)
Centre Hospitalier Universitaire Sainte-Justine
Horizon Awards
Sauvageau
Co-Investigator
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée
477,000
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_
01/04/2022
31/01/2025
2022
James Shapiro (P)
University of Alberta
Horizon Awards
Shapiro
Lead
James Shapiro, Michael Kallos, Timothy Kieffer
2,450,238
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality.
01/04/2022
31/01/2025
2022
Michael Kallos (C)
University of Calgary
Horizon Awards
Shapiro
Co-Investigator
James Shapiro, Michael Kallos, Timothy Kieffer
298,825
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality.
01/04/2022
31/01/2025
2022
Timothy Kieffer (C)
University of British Columbia
Horizon Awards
Shapiro
Co-Investigator
James Shapiro, Michael Kallos, Timothy Kieffer
244,333
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality.
01/04/2022
31/01/2025
2022
Sara Vasconcelos (P)
University Health Network
Horizon Awards
Vasconcelos
Lead
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme
2,270,110
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_
01/04/2022
31/01/2025
2022
Gregory Korbutt (C)
University of Alberta
Horizon Awards
Vasconcelos
Co-Investigator
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme
100,800
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_
01/04/2022
31/01/2025
2022
Michael Laflamme (C)
University Health Network
Horizon Awards
Vasconcelos
Co-Investigator
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme
629,090
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_
01/04/2022
31/01/2025
2022
Juan Carlos Zúñiga-Pflücker (C)
Sunnybrook Health Sciences Centre
Impact Awards
Keller
Co-Investigator
Gordon Keller, Juan Carlos Zúñiga-Pflücker
100,000
Novel human pluripotent stem cell-derived hematopoietic cell therapy
Multiple Diseases
Human pluripotent stem cells, hematopoietic stem cells, T cell progenitors, neutrophil progenitors, cell therapy
Blood disorders, such as leukemia, can be treated or even cured by bone marrow transplantation. The success of this therapy is due to the presence of blood-forming stem cells in bone marrow, that following transplantation, create a new blood-forming system in the patient. While successful, this therapy is limited to patients that have a matched bone marrow (stem cell) donor. A second challenge is that the transplanted stem cells take time to regenerate cells of the immune system , specifically those cells known as T-cells. This delay can leave transplant patients susceptible to life threatening infections. _x000D_
_x000D_
Our research proposed seeks to address these limitations by producing blood-forming stem cells and T cell progenitors in the lab from a specialized type of stem cell known as a human pluripotent stem cell (hPSCs). The proposed experiments build on recent findings from Dr. Keller’s lab showing that it is possible to generate blood forming progenitors from hPSCs. We will optimize the development of these progenitors and demonstrate that they are indeed human blood-forming stem cells. We will also generate T cell progenitors from hPSCs that can rapidly make T cells following transplantation and demonstrate that they can generate function T cells in mice. A successful outcome will move us one step closer to developing novel cell therapies to treat patients with leukemia and other blood cell disorders who currently are unable to receive a bone marrow transplant.
01/04/2022
31/03/2024
2022
Gordon Keller (P)
University Health Network
Impact Awards
Keller
Lead
Gordon Keller, Juan Carlos Zúñiga-Pflücker
149,820
Novel human pluripotent stem cell-derived hematopoietic cell therapy
Multiple Diseases
Human pluripotent stem cells, hematopoietic stem cells, T cell progenitors, neutrophil progenitors, cell therapy
Blood disorders, such as leukemia, can be treated or even cured by bone marrow transplantation. The success of this therapy is due to the presence of blood-forming stem cells in bone marrow, that following transplantation, create a new blood-forming system in the patient. While successful, this therapy is limited to patients that have a matched bone marrow (stem cell) donor. A second challenge is that the transplanted stem cells take time to regenerate cells of the immune system , specifically those cells known as T-cells. This delay can leave transplant patients susceptible to life threatening infections. _x000D_
_x000D_
Our research proposed seeks to address these limitations by producing blood-forming stem cells and T cell progenitors in the lab from a specialized type of stem cell known as a human pluripotent stem cell (hPSCs). The proposed experiments build on recent findings from Dr. Keller’s lab showing that it is possible to generate blood forming progenitors from hPSCs. We will optimize the development of these progenitors and demonstrate that they are indeed human blood-forming stem cells. We will also generate T cell progenitors from hPSCs that can rapidly make T cells following transplantation and demonstrate that they can generate function T cells in mice. A successful outcome will move us one step closer to developing novel cell therapies to treat patients with leukemia and other blood cell disorders who currently are unable to receive a bone marrow transplant.
01/04/2022
31/03/2024
2022
Martin Levesque (P)
Université Laval
Impact Awards
Levesque
Lead
Martin Levesque, Samer Hussein
183,000
Repairing the dopaminergic circuits in Parkinson disease using synucleinopathy resistant neurones grafting
Parkinson's disease is a chronic brain disorder, characterized by the accumulation of toxic protein aggregates and the degeneration of dopamine producing neurons. Cell replacement therapy aims to restore function in the body by replacing lost, or dysfunctional cells by healthy ones. Although recent progress facilitates cell replacement therapy for Parkinson's disease, there are still hurdles to overcome. One major challenge is the survival of the grafted neurons in a brain environment containing these toxic protein aggregates. _x000D_
_x000D_
Our main objective is to develop strategies to promote survival of transplanted dopamine neurons to efficiently restore the dopamine deficiencies. Our aims are designed to propose a solution to an important barrier of the effectiveness of cell transplantation i.e. enhance survival of dopamine neuron engraftment in the pathological brain. Our team provides a uniquely suited combination of expertise in cell transplantation and Parkinson’s disease models to carry the proposed work to successful completion. The work will be carried out in preclinical models of Parkinson’s disease and will contribute to a significant amelioration of cell replacement therapies._x000D_
01/04/2022
31/03/2024
2022
Samer Hussein (C)
Université Laval
Impact Awards
Levesque
Co-Investigator
Martin Levesque, Samer Hussein
67,000
Repairing the dopaminergic circuits in Parkinson disease using synucleinopathy resistant neurones grafting
Parkinson's disease is a chronic brain disorder, characterized by the accumulation of toxic protein aggregates and the degeneration of dopamine producing neurons. Cell replacement therapy aims to restore function in the body by replacing lost, or dysfunctional cells by healthy ones. Although recent progress facilitates cell replacement therapy for Parkinson's disease, there are still hurdles to overcome. One major challenge is the survival of the grafted neurons in a brain environment containing these toxic protein aggregates. _x000D_
_x000D_
Our main objective is to develop strategies to promote survival of transplanted dopamine neurons to efficiently restore the dopamine deficiencies. Our aims are designed to propose a solution to an important barrier of the effectiveness of cell transplantation i.e. enhance survival of dopamine neuron engraftment in the pathological brain. Our team provides a uniquely suited combination of expertise in cell transplantation and Parkinson’s disease models to carry the proposed work to successful completion. The work will be carried out in preclinical models of Parkinson’s disease and will contribute to a significant amelioration of cell replacement therapies._x000D_
01/04/2022
31/03/2024
2022
Milica Radisic (P)
University Health Network
Impact Awards
Radisic
Lead
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman
145,000
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack.
01/04/2022
31/03/2024
2022
Gordon Keller (C)
University Health Network
Impact Awards
Radisic
Co-Investigator
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman
30,000
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack.
01/04/2022
31/03/2024
2022
Michael Laflamme (C)
University Health Network
Impact Awards
Radisic
Co-Investigator
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman
10,000
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack.
01/04/2022
31/03/2024
2022
Slava Epelman (C)
University Health Network
Impact Awards
Radisic
Co-Investigator
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman
65,000
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack.
01/04/2022
31/03/2024
2022
Lucie Germain (P)
Université Laval
Impact Awards
Germain
Lead
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin
223,272
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/04/2022
31/03/2024
2022
Bartha Knoppers (C)
McGill University
Impact Awards
Germain
Co-Investigator
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin
10,000
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/04/2022
31/03/2024
2022
Elena Pope (C)
The Hospital for Sick Children
Impact Awards
Germain
Co-Investigator
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin
5,000
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/04/2022
31/03/2024
2022
Manuel Caruso (C)
Université Laval
Impact Awards
Germain
Co-Investigator
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin
7,200
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/04/2022
31/03/2024
2022
Véronique Moulin (C)
Université Laval
Impact Awards
Germain
Co-Investigator
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin
4,528
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds.
01/04/2022
31/03/2024
2022
Bernard Thébaud (P)
Ottawa Hospital Research Institute
Impact Awards
Thébaud
Lead
Bernard Thébaud
249,976
Ironman – Improved Respiratory Outcome of Newborns with Modified Angiogenic Nanovesicles
High blood pressure in the lungs (pulmonary hypertension, PH) complicates lung diseases in babies with overly small lungs. PH doubles the risk of death, and survivors have long-term health problems that can reach into adulthood. Today, there is no effective treatment for severe PH. Our lab showed that specific cells (endothelial progenitor cells or EPCs) can make new blood vessels and stimulate lung growth and lower PH. These cells act like “smart local pharmacies” by releasing tiny particles (extra-cellular vesicles or EV) that contain factors to instruct new blood vessels to grow. We are using a new, induced pluripotent-derived EPC that can be easily and consistently produced in very high quantities. We will test if the EVs from these cells are safe and effective in lab experiments. If so, our innovation will bring a breakthrough treatment that will save lives and improving the quality of life of babies with PH. Our discovery will deliver economic, social and health benefits for Canadians and patients around the world that suffer from diseases with low blood supply such as heart attack, stroke or preeclampsia (high blood pressure in pregnant women that puts the life of both mother and baby at risk; it often leads to a C-section and preterm delivery). This new cell product has potential for commercialization and job creation. It has already led our partner Dr. Yoder to create a company (Vascugen) with the goal of manufacturing a new cell product to be used in patients.
01/04/2022
31/03/2024
2022
Lauren Flynn (P)
University of Western Ontario
Impact Awards
Flynn
Lead
Lauren Flynn, John Ronald
230,000
Delivery of adipose-derived stromal cells within novel cell-assembled bioscaffolds for the treatment of chronic wounds
Chronic or non-healing skin wounds are a significant and growing clinical problem that occurs frequently in diabetics, individuals with vascular disease, and patients who are elderly or have mobility restrictions, negatively affecting their overall health and quality of life. Treating these wounds is costly and places a substantial burden on the Canadian healthcare system. Unfortunately, current wound dressings fail to address the underlying biological dysfunction within the wound bed, resulting in unpredictable outcomes and treatment times that often extend beyond 20 weeks. In cases where the wound fails to heal, amputation of the affected limb may be required. The proposed research addresses the critical need for new chronic wound treatments. Our team has designed novel cell therapies derived from human fat discarded as surgical waste that can naturally promote blood vessel formation and soft tissue regeneration. In the current project, our interdisciplinary team of experts will perform pre-clinical testing using established mouse and pig models to validate that our patented cell therapy platform can robustly and reproducibly stimulate healing. This data will allow us to advance towards clinical trials in humans and demonstrate proof-of-concept of our promising technology to potential industry partners in the wound care sector who could aid in commercialization and clinical translation, helping to position Canada as a leader in the advanced wound care field.
01/04/2022
31/03/2024
2022
John Ronald (C)
University of Western Ontario
Impact Awards
Flynn
Co-Investigator
Lauren Flynn, John Ronald
20,000
Delivery of adipose-derived stromal cells within novel cell-assembled bioscaffolds for the treatment of chronic wounds
Chronic or non-healing skin wounds are a significant and growing clinical problem that occurs frequently in diabetics, individuals with vascular disease, and patients who are elderly or have mobility restrictions, negatively affecting their overall health and quality of life. Treating these wounds is costly and places a substantial burden on the Canadian healthcare system. Unfortunately, current wound dressings fail to address the underlying biological dysfunction within the wound bed, resulting in unpredictable outcomes and treatment times that often extend beyond 20 weeks. In cases where the wound fails to heal, amputation of the affected limb may be required. The proposed research addresses the critical need for new chronic wound treatments. Our team has designed novel cell therapies derived from human fat discarded as surgical waste that can naturally promote blood vessel formation and soft tissue regeneration. In the current project, our interdisciplinary team of experts will perform pre-clinical testing using established mouse and pig models to validate that our patented cell therapy platform can robustly and reproducibly stimulate healing. This data will allow us to advance towards clinical trials in humans and demonstrate proof-of-concept of our promising technology to potential industry partners in the wound care sector who could aid in commercialization and clinical translation, helping to position Canada as a leader in the advanced wound care field.
01/04/2022
31/03/2024
2022
Molly Shoichet (P)
University of Toronto
Impact Awards
Shoichet
Lead
Molly Shoichet, Andras Nagy, Cindi Morshead
110,000
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_
01/04/2022
31/03/2024
2022
Andras Nagy (C)
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Impact Awards
Shoichet
Co-Investigator
Molly Shoichet, Andras Nagy, Cindi Morshead
30,000
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_
01/04/2022
31/03/2024
2022
Cindi Morshead (C)
University of Toronto
Impact Awards
Shoichet
Co-Investigator
Molly Shoichet, Andras Nagy, Cindi Morshead
110,000
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_
01/04/2022
31/03/2024
2022
Pamela Hoodless (P)
University of British Columbia
Impact Awards
Hoodless
Lead
Pamela Hoodless
250,000
Pathways of Cell Identity in Human Liver Organoids
Multiple Diseases
Liver, Organoids, Human pluripotent stem cells, Signal Transduction, Cell-cell interactions, Lineage Tracing
Liver disorders re a leading cause of death worldwide. Non-alcoholic fatty liver disease affects over 7 million Canadians and liver cancer is fastest rising cancer in Canada. Current treatments for chronic liver disease focus on slowing progression and minimizing complications, such as hypertension. Liver transplantation is a potential cure, but is dependent on donor availability._x000D_
_x000D_
Recent advances in the generation of hepatocytes, the main functional cell in the liver, from human pluripotent stem cells (hPSCs) have excited researchers by providing a potential source of cells for transplants, drug testing and bioarticial liver devices. Current methods of making hepatocytes in a dish from hPSCs do not produce fully functional hepatocytes. Moreover, other types of cells that are needed for a proper functioning liver are rarely included. To improve methods, we need to better understand how heaptocytes interact with other cell types during development to create a fully functional liver._x000D_
_x000D_
Our project will generate livers from hPSCs using multi-cellular, 3D organoid cultures, often called 'mini-livers'. Importantly, these organoids contain many of the different types of cells necessary for liver functions. We will use state-of-the-art methods to understand how different cells are related in organoids and will explore the cellular environment which drives liver development. Our project will address how close organoids are to normal liver development and how they may be improved.
01/04/2022
31/03/2024
2022
Karun Singh (P)
University Health Network
Impact Awards
Singh
Lead
Karun Singh, Sarah Wootton
235,000
Gene therapy to restore neural connectivity in neurodevelopmental disorders associated with a CNV microdeletion
The 15q13.3 deletion is a neurodevelopmental disorder (NDD) that manifests early during postnatal life and is associated with epilepsy, schizophrenia, autism spectrum disorder and developmental delay. It is a genetic disorder caused by the loss of a small piece of genetic material (DNA), and is recurrently found in genetic studies, occurring in 1 in 2500-5000 individuals. The genomic region affected typically contains ~10 genes. There are no treatments that reverse or cure the symptoms and impairments experienced by individuals, which cause life-long disabilities. We recently identified that one of the ten genes (OTUD7A) in this genetic region may be responsible to for mediating a major portion of the clinical outcomes associated with this deletion. To understand how OTUD7A contributes to abnormal brain function, we performed a novel screen to identify which proteins interact with OTUD7A and revealed that it regulates signaling molecules through a process named protein homeostasis, which is the regulation of protein levels. In this project, we will examine whether the loss of OTUD7A function impairs axonal and synaptic development using patient stem cell-derived neural cells as models. We hypothesize that abnormal protein homeostasis of targets of OTUD7A contributes to defective synaptic development and neural plasticity, its. We will also test a gene therapy strategy to restore OTUD7A function and regenerate defective neural circuits in patient-derived neural cells.
01/04/2022
31/03/2024
2022
Sarah Wootton (C)
University of Guelph
Impact Awards
Singh
Co-Investigator
Karun Singh, Sarah Wootton
15,000
Gene therapy to restore neural connectivity in neurodevelopmental disorders associated with a CNV microdeletion
The 15q13.3 deletion is a neurodevelopmental disorder (NDD) that manifests early during postnatal life and is associated with epilepsy, schizophrenia, autism spectrum disorder and developmental delay. It is a genetic disorder caused by the loss of a small piece of genetic material (DNA), and is recurrently found in genetic studies, occurring in 1 in 2500-5000 individuals. The genomic region affected typically contains ~10 genes. There are no treatments that reverse or cure the symptoms and impairments experienced by individuals, which cause life-long disabilities. We recently identified that one of the ten genes (OTUD7A) in this genetic region may be responsible to for mediating a major portion of the clinical outcomes associated with this deletion. To understand how OTUD7A contributes to abnormal brain function, we performed a novel screen to identify which proteins interact with OTUD7A and revealed that it regulates signaling molecules through a process named protein homeostasis, which is the regulation of protein levels. In this project, we will examine whether the loss of OTUD7A function impairs axonal and synaptic development using patient stem cell-derived neural cells as models. We hypothesize that abnormal protein homeostasis of targets of OTUD7A contributes to defective synaptic development and neural plasticity, its. We will also test a gene therapy strategy to restore OTUD7A function and regenerate defective neural circuits in patient-derived neural cells.
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators.
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators.
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators.
01/04/2022
31/01/2025
2022
Amy Zarzeczny (P)
University of Regina
Translation & Society Team Award
Zarzeczny
Lead
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu
250,465
Law, Public Policy and Social License for Next-Generation Regenerative Medicine
ELSI
Regenerative medicine, law, policy, regulation, governance, public perception, social license
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public.
01/04/2022
31/01/2025
2022
Timothy Caulfield (C)
University of Alberta
Translation & Society Team Award
Zarzeczny
Co-Investigator
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu
265,830
Law, Public Policy and Social License for Next-Generation Regenerative Medicine
ELSI
Regenerative medicine, law, policy, regulation, governance, public perception, social license
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public.
01/04/2022
31/01/2025
2022
Ubaka Ogbogu (C)
University of Alberta
Translation & Society Team Award
Zarzeczny
Co-Investigator
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu
188,690
Law, Public Policy and Social License for Next-Generation Regenerative Medicine
ELSI
Regenerative medicine, law, policy, regulation, governance, public perception, social license
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public.
01/04/2022
31/01/2025
2022
Manoj Lalu (P)
Ottawa Hospital Research Institute
Translation & Society Team Award
Lalu
Lead
Manoj Lalu
300,000
Engaging patients in laboratory-based cell therapy research: Co-production and field testing of a framework
ELSI
patient engagement, patient and public involvement, patient oriented research
Patient engagement in research means patients are partners on a research team to provide input on various matters. While this practice is becoming more common in clinical (human) research, it is less often used in lab (cell/animal) research. We believe engaging patients in SCN funded research is important. We want to develop guidance for researchers and patient partners in this area. Our team previously identified all lab studies that included patient engagement and interviewed scientists and patients involved. Although few studies were identified, we found that patients can be involved in various aspects of lab research, including identifying priorities and presenting findings. Patient engagement improved researchers’ understanding of the real-life implications of their work, while patient partners gained new insights into biomedical research. _x000D_
_x000D_
The main aim of our project is to identify how SCN funded researchers and patient partners can work together on lab studies and to identify methods that will improve this process. This guidance will be co-developed alongside a team of patients and cell therapy/regenerative medicine researchers. We will also invite SCN lab groups (including trainees) and patients to test the framework, and then participate in focus groups to ask for their feedback. The developed guidance will outline promising practices for patient engagement in preclinical cell therapy research and allow more partnerships to be formed.
01/04/2022
31/01/2025
2023
Bruce Verchere (P)
University of British Columbia
Accelerating Clinical Translation Award
Verchere
Lead
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
188,000
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes
Diabetes
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR.
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes.
01/04/2023
31/01/2025
2023
Francis Lynn (C)
University of British Columbia
Accelerating Clinical Translation Award
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
188,000
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes
Diabetes
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR.
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes.
01/04/2023
31/01/2025
2023
Megan Levings (C)
University of British Columbia
Accelerating Clinical Translation Award
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
188,000
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes
Diabetes
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR.
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes.
01/04/2023
31/01/2025
2023
Timothy Kieffer (C)
University of British Columbia
Accelerating Clinical Translation Award
Verchere
Co-Investigator
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer
36,000
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes
Diabetes
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR.
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes.
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients.
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients.
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients.
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients.
01/04/2023
31/01/2025
2023
Juan Carlos Zúñiga-Pflücker (P)
Sunnybrook Research Institute
Accelerating Clinical Translation Award
Zúñiga-Pflücker
Lead
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
407,375
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM)
Immunotherapy; cancer
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
01/04/2023
31/01/2025
2023
Donna Wall (C)
The Hospital for Sick Children
Accelerating Clinical Translation Award
Zúñiga-Pflücker
Co-Investigator
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
101,500
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM)
Immunotherapy; cancer
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
01/04/2023
31/01/2025
2023
Jonas Mattsson (C)
University Health Network
Accelerating Clinical Translation Award
Zúñiga-Pflücker
Co-Investigator
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson
91,000
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM)
Immunotherapy; cancer
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases.
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases.
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases.
01/04/2023
31/01/2025
2023
Peter Zandstra (P)
University of British Columbia
Accelerating Clinical Translation Award
Zandstra
Lead
Peter Zandstra, Yale Michaels
218,034
PSC-derived immune cells as an advanced delivery vehicle for protein therapeutics
Protein Therapeutics
Stem cells, B cells, inflammation, synthetic biology, developmental immunology
Our aim is to address the challenge of treating chronic inflammatory disease, a group of conditions that impact more than 6 million Canadians. Protein-based medicines called biologics can effectively treat inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis. Unfortunately, for these biologics to be effective, they must be dosed by injections every few weeks. These injections are painful and cause the medicine to travel all over the body leading to side-effects. Furthermore, frequent treatments with biologics are expensive- they can cost more than $70,000 per year per patient. Our goal is to address these limitations by using living cells to make and release biologics from within the body. We are using a type of immune cell called a B cell for this job because B cells can survive in the body for decades and can make and release large quantities of protein. We plan to genetically modify B cells so that they will only make and release their therapy when they sense inflammation within the body. This will help avoid unwanted side effects. Rather than getting B cells from human donors, which is very expensive, we will make our B cell product from human stem cells which can be grown extensively outside of the body. This will allow us to make an affordable medicine that will be accessible to patients. This project will help our partner organisation, Apiary Therapeutics, grow as a company and continue to hire highly skilled Canadians.
01/04/2023
31/01/2025
2023
Yale Michaels (C)
CancerCare Manitoba
Accelerating Clinical Translation Award
Zandstra
Co-Investigator
Peter Zandstra, Yale Michaels
181,966
PSC-derived immune cells as an advanced delivery vehicle for protein therapeutics
Protein Therapeutics
Stem cells, B cells, inflammation, synthetic biology, developmental immunology
Our aim is to address the challenge of treating chronic inflammatory disease, a group of conditions that impact more than 6 million Canadians. Protein-based medicines called biologics can effectively treat inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis. Unfortunately, for these biologics to be effective, they must be dosed by injections every few weeks. These injections are painful and cause the medicine to travel all over the body leading to side-effects. Furthermore, frequent treatments with biologics are expensive- they can cost more than $70,000 per year per patient. Our goal is to address these limitations by using living cells to make and release biologics from within the body. We are using a type of immune cell called a B cell for this job because B cells can survive in the body for decades and can make and release large quantities of protein. We plan to genetically modify B cells so that they will only make and release their therapy when they sense inflammation within the body. This will help avoid unwanted side effects. Rather than getting B cells from human donors, which is very expensive, we will make our B cell product from human stem cells which can be grown extensively outside of the body. This will allow us to make an affordable medicine that will be accessible to patients. This project will help our partner organisation, Apiary Therapeutics, grow as a company and continue to hire highly skilled Canadians.
01/04/2023
31/01/2025
2023
Sowmya Viswanathan (P)
University Health Network
Clinical Trial Awards
Viswanathan
Lead
Sowmya Viswanathan
750,000
Autologous Bone Marrow Aspirate Concentrate or Lipoaspirate Concentrate for OsteoArthritis: ABLE OA Clinical Trial
Joint pain and disability affect 1 in 6 Canadians. There is no cure; patients manage their pain with short lasting treatments. In this clinical trial, we are looking to test two types of preparations that are made from the patient’s bone marrow or fat. These preparations have been used to treat painful joints for years. Health Canada decided to require additional proof in well designed and controlled clinical trials before these preparations could be offered routinely to all patients. The clinical trial we are proposing is well designed; patients are randomly selected to be part of a treatment arm where they will receive their own bone marrow or fat, or a placebo arm, where they will be injected with salt water. They will not know which arm they are in, nor will the clinicians. This design allows us to isolate the real effect from this “placebo” effect. We expect patients in the treatment arm to have greater pain relief and better ability to perform daily activities. Our trial is not only well designed but also answers basic biology questions about why some patients respond well while others do not. We think this is because some patients have more inflammation in their joints and body. We will match the level of inflammation in patients to whether the patients respond well or not. Altogether, our trial will provide access to Canadian patients to new treatments to manage their joint pain and disability and help answer fundamental questions about how these treatments work.
01/04/2023
31/01/2025
2023
Marc Jeschke (P)
McMaster University
Clinical Trial Awards
Jeschke
Lead
Marc Jeschke
298,000
A phase I, single-blind, randomized study of safety of cellularized Integra® using autologous burn-derived MSCs
The single most important factor that determines survival of a burn patient is wound healing. We recently made a discovery that could revolutionize management of burn patients when we isolated cells identified as burn-derived mesenchymal stem cells (BD-MSCs) from discarded burned skin. We then developed Integra®-SC a skin substitute that was engineered by incorporating BD-MSCs into Integra®, a dermal matrix, and found beneficial results in both small and large animal models. We now propose to conduct a first-in-humans clinical trial at an academic hospital in Ontario. We will use Integra®-SC, developed from a patient’s own surgically removed burned tissue, to place on their excised burn wounds. We believe that Integra®-SC will facilitate and improve wound healing, heal faster, and, in the long-term, result in less scar formation. Burn surgeons can utilize Integra®-SC to avoid surgically removing a patient’s own good uninjured skin to use as a donor. Donor sites also need to heal, are often sources of pain, and can scar. This study will be done in stages followed by interim safety analyses. After safety analyses, we will evaluate any needs or gaps in order to include recruitment of patients with a larger percent total body surface area burn. The clinical applicability of Integra®-SC is promising and could create a new standard for burn patients in Ontario and worldwide, further providing a broader clinical application and impacts patients with traumatic and complex wounds.
01/04/2023
31/01/2025
2023
Lucie Germain (P)
Université Laval
Clinical Trial Awards
Germain
Lead
Lucie Germain
603,600
Clinical trial of cultured epithelial corneal autografts for the treatment of Canadians with limbal stem cell deficiency
Limbal stem cell deficiency (LSCD) is a severe disease caused by damage or decrease of stem cells in an area of the eye called the “corneal limbal region,” following trauma or disease. The LOEX/CHU de Québec-Université Laval, a leader in cell therapies, is performing the first clinical trial in Canada offering a treatment for LSCD using “cultured epithelial corneal autograft (CECA).” The CECA involves taking a small piece of tissue from the healthy eye to grow cells to produce CECA and then grafting it back into the affected eye. The LOEX has been successfully producing CECA since 2012. _x000D_
Our interdisciplinary team brings together experts in tissue-engineering and economic, ethical/legal issues, ophthalmology, pathology, research professionals and also a patient representative. _x000D_
The objective of the present proposal is to continue our multicenter (Quebec, Montreal and Toronto) clinical trial to evaluate the effectiveness and safety of the CECA treatment. We expect to recruit and treat 12 adult patients. The number of patients for the entire clinical study will be 49 adult patients and 5 minor patients._x000D_
Without treatment, LSCD results in severe visual impairments affecting the quality of life of patients and their families. LSCD affects patients' ability to work, drive and conduct daily activities. Therefore, this innovative treatment, if proven successful, could change the lives of Canadian patients affected by this rare disease by improving vision in their affected eye.
01/04/2023
31/01/2025
2023
Michael Fehlings (P)
University Health Network
Fueling Biotechnology Partnerships Awards
Fehlings
Lead
Michael Fehlings
400,000
Translation of cGMP grade oligodenrogenic NPCs (oNPCs) for the treatment of traumatic cervical spinal cord injury
Spinal cord injury
neural stem cells, hiPSC, GMP, spinal cord injury
Spinal cord injuries (SCIs), frequently the result of falls or road traffic accidents, have devastating long-term physical, social, and financial impacts on patients and their families. Currently, there are no effective therapies available for the treatment of SCI. Damage to the spinal cord results in the loss of I) cells critical for sending signals from the brain to the rest of the body and ii) myelin, a substance that insulates nerves to ensure signals can travel efficiently. Without these signals, a person’s ability to perform everyday activities such as walking, grasping, holding and controlling bowel / bladder function is compromised, which results in debilitating impairments such as para/quadriplegia and death. Stem cells show exciting promise for treating SCI patients due to their ability to replace any cell type within the human body. This application focuses on a strategy to repair the injured spinal cord using human stem cells that have been generated to repair the myelin damage frequently observed following a SCI. This work is the culmination of over 16 years of research into the fields of SCI and stem cells by my lab, which has now partnered with Inteligex; the only Canadian-based regenerative medicine company working on a stem cell-based therapy for SCI. The aim of this proposal is to develop this stem cell-based therapeutic approach as a viable treatment option for individuals who sustain a SCI.
01/04/2023
31/01/2025
2023
C. Florian Bentzinger (P)
Université de Sherbrooke
Fueling Biotechnology Partnerships Awards
Bentzinger
Lead
C. Florian Bentzinger
398,600
Mobilizing endogenous repair in muscular dystrophy
Muscular dystrophies (MDs) are a group of rare muscle wasting diseases that often affect kids. To date, no effective treatment options are available for MD. The causes of different forms of MD are highly diverse, which makes it difficult to develop treatments that can be used for all patients. We discovered that in several different mouse models of MD, the ability of muscle to repair itself is strongly reduced. The Canadian Biotechnology company Satellos has identified a drug that is able to correct muscle repair defects by stimulation of tissue-resident stem cells. Here, we propose to partner with Satellos to study the effects of this unique treatment approach in mouse models of two particularly severe forms of MD, try to better understand the molecular changes induced by the drug, and test if it can be combined with other regenerative therapies. The study we propose will lay the ground-work for a much-needed novel and highly efficient drug that can potentially be used to treat many different forms of MD. A stem cell targeted therapeutic agent boosting the innate repair capacity of skeletal muscle represents an unprecedented and disruptive discovery that would pioneer a novel class of therapeutics with the potential to have a dramatic impact on the quality of life of patients affected by these devastating diseases.
01/04/2023
31/01/2025
2023
Massimiliano Paganelli (P)
Centre Hospitalier Universitaire Sainte-Justine
Fueling Biotechnology Partnerships Awards
Paganelli
Lead
Massimiliano Paganelli, Christopher Rose
320,000
iPSC-derived Encapsulated Liver Tissue: extending the indication to acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) consists in an acute decompensation of the vital functions of the liver and other organs happening in people suffering from chronic liver disease. No treatment exists for ACLF other than liver transplantation, which is only possible for only a minority of patients. Over the last 5 years, with the support of the Stem Cell Network, we have developed an innovative treatment consisting in an implantable, stem cell-derived liver tissue that is effective in treating acute forms of liver failure, at least in experimental conditions. With this project we aim at assessing whether this treatment, that we call Encapsulated Liver Tissue (ELT), is also effective in treating ACLF. We will test the behavior of the ELT in the peculiar conditions characterizing ACLF and measure its efficacy in treating ACLF-related complications and improving survival of relevant animal models. If successful, this project will allow expanding the indications of the ELT to ACLF, which in turn will allow us and our partner, the regenerative medicine company Morphocell Technologies, to reach more patients in need.
01/04/2023
31/01/2025
2023
Christopher Rose (C)
Centre Hospitalier de l'Université de Montréal
Fueling Biotechnology Partnerships Awards
Paganelli
Co-Investigator
Massimiliano Paganelli, Christopher Rose
80,000
iPSC-derived Encapsulated Liver Tissue: extending the indication to acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) consists in an acute decompensation of the vital functions of the liver and other organs happening in people suffering from chronic liver disease. No treatment exists for ACLF other than liver transplantation, which is only possible for only a minority of patients. Over the last 5 years, with the support of the Stem Cell Network, we have developed an innovative treatment consisting in an implantable, stem cell-derived liver tissue that is effective in treating acute forms of liver failure, at least in experimental conditions. With this project we aim at assessing whether this treatment, that we call Encapsulated Liver Tissue (ELT), is also effective in treating ACLF. We will test the behavior of the ELT in the peculiar conditions characterizing ACLF and measure its efficacy in treating ACLF-related complications and improving survival of relevant animal models. If successful, this project will allow expanding the indications of the ELT to ACLF, which in turn will allow us and our partner, the regenerative medicine company Morphocell Technologies, to reach more patients in need.
01/04/2023
31/01/2025
2023
Fabio Rossi (P)
University of British Columbia
Fueling Biotechnology Partnerships Awards
Rossi
Lead
Fabio Rossi, Bettina Willie, Frank Rauch
194,121
Bone targeted EP4 agonists as therapeutics for muscular dystrophy
Muscle disease
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2,
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action.
01/04/2023
31/01/2025
2023
Bettina Willie (C)
McGill University
Fueling Biotechnology Partnerships Awards
Rossi
Co-Investigator
Fabio Rossi, Bettina Willie, Frank Rauch
108,740
Bone targeted EP4 agonists as therapeutics for muscular dystrophy
Muscle disease
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2,
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action.
01/04/2023
31/01/2025
2023
Frank Rauch (C)
McGill University
Fueling Biotechnology Partnerships Awards
Rossi
Co-Investigator
Fabio Rossi, Bettina Willie, Frank Rauch
96,960
Bone targeted EP4 agonists as therapeutics for muscular dystrophy
Muscle disease
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2,
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action.
01/04/2023
31/01/2025
2023
Jason Guertin (P)
Université Laval
Impact Awards: ELSI Stream
Guertin
Lead
Jason Guertin
200,000
Supporting the use of early economic evaluations within the regenerative medicine field
Though health technologies must be effective before they are made widely available to Canadians, healthcare systems often require they be cost-effective as well. Unfortunately, expertise regarding the economic components of regenerative medicine technologies is scarce._x000D_
_x000D_
This proposal combines a series of real-world projects aimed at examining the cost of a specific regenerative medicine technology, the self-assembled skin substitute (SASS), which is currently being used to treat severely burned patients. Once complete, we will use the experience gained in this first series of projects to design a series of knowledge mobilization tools tailored to fundamental and clinical researchers so as to help them plan their own future economic studies._x000D_
_x000D_
By doing so, we will not only help bring an innovative technology, SASS, to Canadians but also help other Canadian researchers plan economic studies that will be required for the technologies they are creating.
01/04/2023
31/01/2025
2023
Manoj Lalu (P)
Ottawa Hospital Research Institute
Impact Awards: ELSI Stream
Lalu
Lead
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz
101,142
Developing guidance to translate promising cell therapies to early phase clinical trials
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials.
01/04/2023
31/01/2025
2023
Jonathan Kimmelman (C)
McGill University
Impact Awards: ELSI Stream
Lalu
Co-Investigator
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz
15,000
Developing guidance to translate promising cell therapies to early phase clinical trials
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials.
01/04/2023
31/01/2025
2023
Dean Fergusson (C)
Ottawa Hospital Research Institute
Impact Awards: ELSI Stream
Lalu
Co-Investigator
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz
53,859
Developing guidance to translate promising cell therapies to early phase clinical trials
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials.
01/04/2023
31/01/2025
2023
Agnes Grudniewicz (C)
University of Ottawa
Impact Awards: ELSI Stream
Lalu
Co-Investigator
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz
30,000
Developing guidance to translate promising cell therapies to early phase clinical trials
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials.
01/04/2023
31/01/2025
2023
Colin Crist (P)
Sir Mortimer B. Davis-Jewish General Hospital
Impact Awards
Crist
Lead
Colin Crist
250,000
Shining light on muscle regeneration: MuSC mediated delivery of optogenetic contractile properties to skeletal muscle
Muscle disease
Muscle stem cell, ex vivo expansion, genetic manipulation, channelrhodopsin, optogenetics
Skeletal muscle is required for all voluntary movement and is also an important thermogenic organ in adult vertebrates. Although skeletal muscle has a remarkable muscle stem cell (MuSC) dependent capacity for regeneration, it is subject to several diseases, including a large family of muscular dystrophies as well as muscle wasting associated with cancer (cachexia) and aging (sarcopenia). Moreover, loss of muscle strength and paralysis of specific muscle groups can endure in survivors of stroke and spinal cord injury. New therapeutic strategies to restore muscle function are urgently needed._x000D_
_x000D_
Cell based therapies for muscle disease have been envisioned for decades. Although early clinical trials suggest that donor cell transplantation by intramuscular injection is safe, three major hurdles need to be overcome include our inability to expand rare muscle stem cells (MuSCs, the cells that are normally responsible for lifelong regeneration of skeletal muscle), inability to deliver donor myogenic cells systemically through the blood stream, and poor mobility of MuSCs from sites of intramuscular injection. _x000D_
_x000D_
Our vision is to engineer designer, off-the-shelf MuSCs that will evade immune surveillance, engraft into skeletal muscle and turn the myofibre into a therapeutic molecule synthesis platform. Our mission is to take advantage of our MuSC expansion conditions to generate designer MuSCs that will impart contractile properties to skeletal muscle when stimulated with light.
01/04/2023
31/01/2025
2023
Zachary Laksman (P)
University of British Columbia
Impact Awards
Laksman
Lead
Zachary Laksman
249,997
Development of high-throughput assays to stratify cardiotoxic drug risk by sex and genotype
Heart disease
drug safety, drug development, personalized medicine, tissue engineering, translational medicine, genetic heart disease
An important consideration in the development of new medications is side effects. If new drugs are tested and found to affect the heart, those drugs are not considered safe. We will make more accurate tests for the side effects of drugs on the heart. To do this, we will use a “heart in a dish” model to test drugs. In this model, we engineer heart cells so that we can study how they beat in the dish, and how the beat changes in response to drugs._x000D_
Our model will be an improvement on earlier work in several ways. It will use cells that are more like the cells found in adult hearts. We will separately test both male and female cells. We will consider the roles of increased heart rate and the strength of contraction of the beating cells. We will also test whether a very common mutation changes how the cells respond to drugs. In the future, we will be able to test for personalized responses to drugs. This will make medications safer for everybody. _x000D_
01/04/2023
31/01/2025
2023
Yale Michaels (P)
CancerCare Manitoba
Impact Awards
Michaels
Lead
Yale Michaels, David Knapp
185,290
Cellular engineering to enhance T cell production from pluripotent stem cells
T cells are a type of immune cell that protects us from infection. T cells can also be used to treat diseases such as cancer. T cells are removed from a patient’s blood and genetically modified so that they can recognize and kill cancer cells before being returned to the patient’s body. These engineered T cell therapies are very effective with cure-rates above 50% for some types of blood cancer but they are also extremely expensive, costing about $500,000 per patient. To make these treatments cheaper, scientists are trying to produce T cells in the lab from stem cells using a process called in vitro differentiation. By making large quantities of T cells from stem cells in the lab, we can make one product to treat many patients, a much cheaper approach than manufacturing a new personal T cell therapy for each individual. The goal of our project is to make in vitro differentiation more efficient and less expensive so we can bring down the overall cost of T cell therapy and help more patients access these life-saving treatments. Previously, stem cells have been turned into T cells by feeding them complex formulas of proteins and small molecules. Our team is using our expertise in gene editing to make genetically engineered stem cells that know how to become T cells with a reduced reliance on expensive proteins. Our work will contribute to cheaper T cell manufacturing and build Canadian scientific excellence in genetic engineering of stem cells.
01/04/2023
31/01/2025
2023
David Knapp (C)
Université de Montréal
Impact Awards
Michaels
Co-Investigator
Yale Michaels, David Knapp
64,667
Cellular engineering to enhance T cell production from pluripotent stem cells
T cells are a type of immune cell that protects us from infection. T cells can also be used to treat diseases such as cancer. T cells are removed from a patient’s blood and genetically modified so that they can recognize and kill cancer cells before being returned to the patient’s body. These engineered T cell therapies are very effective with cure-rates above 50% for some types of blood cancer but they are also extremely expensive, costing about $500,000 per patient. To make these treatments cheaper, scientists are trying to produce T cells in the lab from stem cells using a process called in vitro differentiation. By making large quantities of T cells from stem cells in the lab, we can make one product to treat many patients, a much cheaper approach than manufacturing a new personal T cell therapy for each individual. The goal of our project is to make in vitro differentiation more efficient and less expensive so we can bring down the overall cost of T cell therapy and help more patients access these life-saving treatments. Previously, stem cells have been turned into T cells by feeding them complex formulas of proteins and small molecules. Our team is using our expertise in gene editing to make genetically engineered stem cells that know how to become T cells with a reduced reliance on expensive proteins. Our work will contribute to cheaper T cell manufacturing and build Canadian scientific excellence in genetic engineering of stem cells.
01/04/2023
31/01/2025
2023
Martin Post (P)
The Hospital for Sick Children
Impact Awards
Post
Lead
Martin Post, Andras Nagy
215,960
Enhancing the production of human alveolar-like macrophages for lung cancer therapy
We have made specialized immune cells from animal stem cells that can clean up diseased cells, viruses, and bacteria in the airways of mice and improve short and long-term lung disease outcomes. We have also made these specialized immune cells from human stem cells. Cell growth of human immune cells slows over time; therefore, to scale our production to clinically relevant cell numbers for human use, we will temporarily change these immune cells into faster growing pre-immune cells by insertion of specific genes that can be switched on and off. Switching them on for a defined time will lead to a large pool of these cells that then can be converted back to the original immune cells. Our aim is to use these cells to target, kill and clear solid lung cancer tumours. To accomplish this, the human immune cells will be modified to display a mutant protein on their cell surface that allows the immune cell to interact, kill and remove tumour cells. We have shown in similar animal-derived immune cells that this modification promotes tumour cell death and removal. We will test the killing capacity of these modified human immune cells by culturing them together with patient-derived cancer cells that are grown in a 3D organ-like structure. This will determine the efficacy of our new immune-cell technology for targeting solid lung tumours, an area of cancer research that has lacked innovation for several decades despite very poor survival rates and a high healthcare burden in Canada.
01/04/2023
31/01/2025
2023
Andras Nagy (C)
Sinai Health System
Impact Awards
Post
Co-Investigator
Martin Post, Andras Nagy
34,040
Enhancing the production of human alveolar-like macrophages for lung cancer therapy
We have made specialized immune cells from animal stem cells that can clean up diseased cells, viruses, and bacteria in the airways of mice and improve short and long-term lung disease outcomes. We have also made these specialized immune cells from human stem cells. Cell growth of human immune cells slows over time; therefore, to scale our production to clinically relevant cell numbers for human use, we will temporarily change these immune cells into faster growing pre-immune cells by insertion of specific genes that can be switched on and off. Switching them on for a defined time will lead to a large pool of these cells that then can be converted back to the original immune cells. Our aim is to use these cells to target, kill and clear solid lung cancer tumours. To accomplish this, the human immune cells will be modified to display a mutant protein on their cell surface that allows the immune cell to interact, kill and remove tumour cells. We have shown in similar animal-derived immune cells that this modification promotes tumour cell death and removal. We will test the killing capacity of these modified human immune cells by culturing them together with patient-derived cancer cells that are grown in a 3D organ-like structure. This will determine the efficacy of our new immune-cell technology for targeting solid lung tumours, an area of cancer research that has lacked innovation for several decades despite very poor survival rates and a high healthcare burden in Canada.
01/04/2023
31/01/2025
2023
Arvind Mer (P)
University of Ottawa
Impact Awards
Mer
Lead
Arvind Mer, Alexandre Blais
144,000
Decoding Alternative Splicing Regulatory Networks in Myogenic Stem Cell Function
Muscle stem cells also known as satellite cells are critical components of skeletal muscle repair after injury. In healthy tissue, satellite cells are undifferentiated and quiescent. Upon injury, they respond quickly and become activated, start proliferation, and differentiate to generate new cells that replace injured cells. Furthermore, a small fraction of the satellite cells will be generated for future use, by avoiding differentiation and returning to the quiescent state. Multiple regulatory mechanisms tightly control each step of this process. However, a key problem in the field is that we don’t fully understand how these fates (quiescence, activation, differentiation, self-renewal) are established, or what mechanisms determine which fate a cell will adopt. Our research addresses these fundamental questions by using bioinformatics, machine learning and experimental genomics approach. We aim to decipher how the process of alternative splicing regulates satellite cells' activity. Furthermore, we will use machine learning to prioritize drugs that can activate satellite cells and maintain their regeneration potential for the long term. This will have a direct implication in the field of regenerative medicine.
01/04/2023
31/01/2025
2023
Alexandre Blais (C)
University of Ottawa
Impact Awards
Mer
Co-Investigator
Arvind Mer, Alexandre Blais
106,000
Decoding Alternative Splicing Regulatory Networks in Myogenic Stem Cell Function
Muscle stem cells also known as satellite cells are critical components of skeletal muscle repair after injury. In healthy tissue, satellite cells are undifferentiated and quiescent. Upon injury, they respond quickly and become activated, start proliferation, and differentiate to generate new cells that replace injured cells. Furthermore, a small fraction of the satellite cells will be generated for future use, by avoiding differentiation and returning to the quiescent state. Multiple regulatory mechanisms tightly control each step of this process. However, a key problem in the field is that we don’t fully understand how these fates (quiescence, activation, differentiation, self-renewal) are established, or what mechanisms determine which fate a cell will adopt. Our research addresses these fundamental questions by using bioinformatics, machine learning and experimental genomics approach. We aim to decipher how the process of alternative splicing regulates satellite cells' activity. Furthermore, we will use machine learning to prioritize drugs that can activate satellite cells and maintain their regeneration potential for the long term. This will have a direct implication in the field of regenerative medicine.
01/04/2023
31/01/2025
2023
Shinichiro Ogawa (P)
University Health Network
Impact Awards
Ogawa
Lead
Shinichiro Ogawa, Boyang Zhang
158,433
Sustained liver engraftment with bioengineered functionally complete liver tissues
Liver disease
Liver regeneration, human pluripotent stem cell- derived hepatocytes, intrahepatic engraftment
Liver failure can only be treated with a new liver; however, many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Despite the recent progress in stem cell therapy, liver cells produced from stem cells are still dissimilar to adult liver cells in terms of maturity and function and thus engraft poorly in injured livers. Recognizing stem cell-derived liver cells cannot further function as single cells, we propose developing functionally complete liver tissues that place the liver cells in their native environment to support their continuous function and engraftment. We are taking an integrated approach that involves directed stem cell differentiation and bioengineered tissue assembly to develop the first functionally complete liver tissue that will possess perfusable blood vessels for nutrient delivery, bile ductal networks for bile acid clearance. We will demonstrate the long-term sustained engraftment of our engineered liver, overcoming the existing low efficacy in stem cell-based liver regenerative therapy. Beyond regenerative medicine, the developed platform and tissues will also find broad applications in drug toxicity and metabolism screening. Ultimately, this work will provide the foundation for the successful clinical translation of stem cell therapy to Canadians living with liver diseases.
01/04/2023
31/01/2025
2023
Boyang Zhang (C)
McMaster University
Impact Awards
Ogawa
Co-Investigator
Shinichiro Ogawa, Boyang Zhang
90,800
Sustained liver engraftment with bioengineered functionally complete liver tissues
Liver disease
Liver regeneration, human pluripotent stem cell- derived hepatocytes, intrahepatic engraftment
Liver failure can only be treated with a new liver; however, many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Despite the recent progress in stem cell therapy, liver cells produced from stem cells are still dissimilar to adult liver cells in terms of maturity and function and thus engraft poorly in injured livers. Recognizing stem cell-derived liver cells cannot further function as single cells, we propose developing functionally complete liver tissues that place the liver cells in their native environment to support their continuous function and engraftment. We are taking an integrated approach that involves directed stem cell differentiation and bioengineered tissue assembly to develop the first functionally complete liver tissue that will possess perfusable blood vessels for nutrient delivery, bile ductal networks for bile acid clearance. We will demonstrate the long-term sustained engraftment of our engineered liver, overcoming the existing low efficacy in stem cell-based liver regenerative therapy. Beyond regenerative medicine, the developed platform and tissues will also find broad applications in drug toxicity and metabolism screening. Ultimately, this work will provide the foundation for the successful clinical translation of stem cell therapy to Canadians living with liver diseases.
01/04/2023
31/01/2025
2023
Kristin Hope (P)
University Health Network
Impact Awards
Hope
Lead
Kristin Hope
250,000
Harnessing developmentally-guided post-transcriptional HSC drivers to advance in vivo hematopoietic regeneration
Bone marrow transplants
hematopoietic stem cells, in vivo regeneration, xenotransplantation, RNA binding proteins, self-renewal, HSC exhaustion
Blood stem cells carefully control the cells they produce over time, choosing to replicate themselves or make functional blood cells (white & red blood cells, platelets, etc) depending on bodily needs. While adult blood stem cells keep their numbers steady to maintain a healthy blood system, fetal stem cells are hardwired to replicate themselves to establish a stem cell pool that can sustain the blood system throughout life. What controls this early replicative process is poorly understood, but represent an untapped system for promoting much-needed, lifesaving adult stem cell replenishment following blood system-damaging treatments and physiological insults such as chemotherapy, blood stem cell transplant, and infection. We have identified the protein TRIM71 as a potential driver of fetal blood stem cell replication and aim to test if its restoration in adult blood stem cells will encourage their expansion and re-establish blood system maintenance. Using pre-clinical models of blood stem cell defects and characterizing clinical samples that are real-world examples of blood stem cell exhaustion resulting from therapeutic insults we aim to unravel how TRIM71 works to promote stem cells and identify drugs that can mimic these effects. This study will culminate in the identification of new targets for re-establishment of the blood stem cell pool across a wide group of adult patients and ultimately address clinically unmet needs of hematological regenerative medicine therapies.
01/04/2023
31/01/2025
2023
Junio Dort (P)
University of Ottawa
Impact Awards
Dort
Lead
Junio Dort
250,000
Novel therapeutic compounds targeting G-coupled receptors to enhance muscle stem cell function in Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD), a frequent genetic disease affecting young boys, causes severe muscle wasting, resulting in ambulatory and respiratory impairments, and premature death. This degenerative environment leads to chronic inflammation that accelerates muscle wasting. Glucocorticoids remain the most efficient drugs that reduce the progression of the disease; however, its positive effect is limited to a few years. Glucocorticoids also have many detrimental side effects. A class of pharmacological compounds called ‘bioactive lipid receptor agonists’ could represent the future of the conventional treatment for DMD. In various inflammatory diseases, the use of these compounds decreases inflammation without harmful side effects. But the therapeutic effect of these compounds is not known on skeletal muscle. The objective of this research project is to investigate the efficacity of these compounds to repair muscles affected by DMD. We will use cells from dystrophic mice and from patients with DMD, as well as the mdx-DBA/2J mice (a well characterized model of DMD) to characterize the beneficial effect of these compounds compared to glucocorticoids. This research project will demonstrate the efficacy of bioactive lipid receptor agonists to reduce inflammation and enhance muscle repair. This will clearly contribute to the development of a more potent treatment for DMD as compared to glucocorticoids.
01/04/2023
31/01/2025
2023
Yan Burelle (P)
University of Ottawa
Impact Awards
Burelle
Lead
Yan Burelle
224,520
Targeting mitochondrial quality control to promote muscle regeneration.
Dysfunction of mitochondria, the cellular powerhouses, plays an important role in a plethora human disorders, including rare genetic myopathies such as Duchenne Muscular Dystrophy (DMD). Mitochondrial dysfunction also causes stem cell abnormalities in several tissues including skeletal muscle. For this reason, modulation of mitochondrial quality is increasingly proposed as a therapeutic strategy to prevent/restore cellular function. However, our ability to do so in muscle stem cells (MuSCs) is hampered by limited knowledge of pathways regulating mitochondrial quality._x000D_
The proposed work will define how mitophagy (a process degrading damaged mitochondria), is regulated in MuSCs, what pathways are involved, how it affects mitochondrial qualities and MuSC function, and whether mitophagy can be targeted to better maintain muscle regeneration capacity._x000D_
_x000D_
Three aims are proposed. _x000D_
1) Delineate the role of mitophagy in the maintenance of MuSC regenerative capacity by silencing the expression of Parkin, a key gene regulating mitophagy._x000D_
2) Determine the effect of genetically enhancing mitophagy on MuSC regenerative capacity_x000D_
3) Determine the effect of novel mitophagy stimulating drugs MuSC regenerative capacity_x000D_
_x000D_
This work will clearly establish the role of mitophagy in MuSCs, and provide proof-of-principle data on the therapeutic potential of a novel class of mitophagy enhancers to improve muscle regeneration.
01/04/2023
31/01/2025
2023
James Ellis (P)
The Hospital for Sick Children
Impact Awards
Ellis
Lead
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh
130,000
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_
01/04/2023
31/01/2025
2023
Augusto Zani (C)
The Hospital for Sick Children
Impact Awards
Ellis
Co-Investigator
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh
70,000
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_
01/04/2023
31/01/2025
2023
Ji-Young Youn (C)
The Hospital for Sick Children
Impact Awards
Ellis
Co-Investigator
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh
25,000
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_
01/04/2023
31/01/2025
2023
Karun Singh (C)
University Health Network
Impact Awards
Ellis
Co-Investigator
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh
25,000
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_
Share this page