Grants Approved 2009 - 2010
Partnerships with the Canadian Institutes of Health Research
Eye Stem Cells: Biology and Therapeutic Applications – Sun Life Financial
Primary Investigator: Valerie Wallace, Ottawa Hospital Research InstitutePer Fagerholm, Linköping University, Sweden
May Griffith, Ottawa Hospital Research Institute, University of Ottawa
Bernard Hurley, Ottawa Hospital
Derek van der Kooy, University of Toronto
Carol Schuurmans, University of Calgary
Vincent Tropepe, University of Toronto
Ottawa Hospital Research Institute
Granted: $2.4 million over 5 years, January 2009 - December 2013
Funded by: CIHR - Regenerative Medicine and Nanomedicine, FFB, Sun Life Financial
Stem cell therapies have the potential to benefit more than one million Canadians affected by degenerative eye diseases, such as retinitis pigmentosa, age-related macular degeneration and corneal diseases; all of which cause blindness. By replacing cells that have been lost through disease or injury, stem cell therapies could potentially benefit anyone, at any stage of eye disease.
Together the team hopes to develop better methods for controlling stem cells, so that they can coax these cells into producing different kinds of eye cells, such as retinal and corneal cells. This is currently the greatest obstacle to successful stem cell therapies. They will also develop more efficient transplantation methods that help new eye cells integrate with existing tissue to restore lost vision. And they will work towards combining cells, genes, biomaterials and pharmaceuticals to create an improved artificial cornea.
Novel Gene Therapy Approaches for the Treatment of Retinal Degenerative Diseases
Primary Investigator: Robert Molday, University of British ColumbiaJim Hu, University of Toronto
Bill Hauswirth, University of Florida
Robert Koenekoop, McGill University
Marinko Sarunic, Simon Fraser University
University of British Columbia
Granted: $3 million over 6 years, January 2009 - December 2014
Funded by: CIHR - Regenerative Medicine and Nanomedicine, FFB
The application of gene therapy for retinal degenerative diseases will be investigated in Stargardt macular dystrophy, cone-rod dystrophy, Leber congenital amaurosis (LCA), and retinitis pigmentosa (RP). The strategy is to replace the defective gene with a “new healthy gene” in specific animal models for retinal degenerative diseases with the aim of slowing photoreceptor loss and partially restoring vision. Success in these animal models would lead to future human clinical trials. The recent success in gene therapy for RPE65 has been highly conclusive for LCA; we believe that we can learn from this and advance even more quickly this time.
XIAP Gene Therapy for the Treatment of Retinal Degeneration
Primary Investigator: Catherine Tsilfidis, Ottawa Hospital Research InstituteRobert Korneluk, University of Ottawa
William Hauswirth, University of Florida
David Zacks, Kellogg Eye Center and the University of Michigan
Stuart Coupland, University of Ottawa Eye Institute
Brian Leonard, University of Ottawa Eye Institute
Ottawa Hospital Research Institute
Granted: $1.4 million over 5 years, January 2010 - December 2015
Funded by: CIHR - Institute of Aging, FFB, Jean Boddy and Jim & Colleen Pallister, Scotiabank
Previously funded by FFB: $40,000 over 6 months, July 2009 - December 2009
The goal of this project is to begin testing a new gene therapy in patients, who are losing their vision due to retinal disease, by the end of five years. Dr. Tsilfidis and her team have shown that a gene called XIAP can block this process and prevent retinal cell death. The gene can be delivered to the eye using a virus called Adeno-Associated Virus (AAV). This therapy has proven particularly promising in an experimental model of retinitis pigmentosa, a genetic condition and important cause of blindness in which a large portion of the outer layer of the retina is lost. XIAP gene therapy was able to protect the cells of this critical part of the eye from dying, resulting in significant preservation of vision.
Operating Grants
Gautam Awatramani
Dalhousie UniversityProbing and Repairing Circuits During Retinal Degeneration
Granted: $90,000 over 1 year, July 2009 - June 2010
Dr. Awatramani is leading a team to test and design strategies to restore vision in people already blind from retinal degeneration. The focus is on probing and repairing circuits during retinal degeneration. Dr. Awatramani is part of a team that partially restored vision in animals that were otherwise completely blind from inherited retinal degeneration (Lagali et al., 2008). This breakthrough revealed the importance of reprogramming surviving, non-photoreceptive retinal neurons to be light-responsive.
Outcomes of the research include a better understanding of the bipolar cells (neurons that normally relay signals from rods and cones) and what is most effective way to make them respond beneficially. Light sensitivity, kinetics and responses in animals with restored vision will be measured for development of new treatment theories and pre-clinical tests.
Michel Cayouette
Institut de recherches cliniques de MontréalSpecification of temporal identity in retinal progenitor cells
[Renewal] Granted: $80,000 over 1 year, July 2009 - June 2010
Stem cells are promising source of replacements for photoreceptors lost through degeneration. But to design safe and efficient cell replacement therapies, researchers need to understand the mechanisms that guide formation of the various retinal cell types during normal development. Recently discovered Ikaros, a gene expressed in early retinal progenitor cells; test whether or how it is critical for generating early-born neurons (e.g., photoreceptors).
This will be done through genetically engineered mice (Ikaros-reporter, and mutant (gene-trap) of related gene Pegasus, both already created and in use in his lab); and through gene expression-profiling with gene “chips”.
Gilbert Bernier
Maisonneuve Rosemont HospitalStem Cell Transplantation for the Treatment of Retinal Degenerative Disease
[Renewal] Granted: $50,000 over 1 year, July 2009 - June 2010
In RP and AMD, replacement of lost photoreceptors is one potential way to stop disease progression and restore visual function. Human embryonic stem cells can be expanded and manipulated in culture to produce specific cell types, and recent work revealed that post-mitotic photoreceptor precursors from newborn mice could functionally integrate the retina of adult mice. The goal here to differentiate pluripotent hES cells into photoreceptors in the test tube and test their therapeutic potential in animal models of retinal degeneration.
Bernier and his team will grow hES cells in novel cell culture conditions and inducing them to become rods and cones, by applying chemical factors known to do this; also enhancing survival by engineering them to make their own survival factors; testing integration of transplants with microscopy and electrophysiology.
Robert Koenekoop
McGill UniversityIdentifying novel Leber congenital amaurosis genes using novel strategies
[Renewal] Granted: $50,000 over 1 year, July 2009 - June 2010
This project will identify new genes and mutations responsible for Leber congenital amaurosis (LCA), the severest human retinal dystrophy and the most common cause of inherited childhood blindness.
Dr. Koenekoop will explore genes that encode for proteins known to interact with the protein, lebercilin, encoded by the gene in which mutations cause LCA5 (“the lebercilin interactome”) as well as other proteins involved in structure and maintenance of the photoreceptors’ ciliary backbone (the “ciliary proteome”), to identify new LCA candidate genes.
Graduate Student Scholarships
Elizabeth M. Kita
FFB and Alberta Heritage Foundation for Medical Research (AHFMR) PartnershipUniversity of Calgary
Supervisor: Sarah McFarlane, Ph.D.
The Expression and Function of Class 3 Semaphorins in the Developing Retina
Awarded: $100,000 over 5 years, January 2010 - December 2015
Blindness can be caused by damage to retinal cells that link the eye to the brain, as in glaucoma. But there is hope that sight might be restored by replacing the damaged cells and by guiding them to make the right connections in the brain. Under the supervision of Prof. Sarah McFarlane, Ms. Elizabeth Kita is studying proteins called semaphorins, which act like signs to direct these connections during development. By learning to read these signs and understand how they work, we might use them to guide re-growth of eye-brain connections and thus restore vision in many blind people.