Dr. Catherine Tsilfidis

​Ottawa Research Institute

XIAP Gene Therapy for the Treatment of Retinal Degeneration: Safety and Toxicity Studies for Translation into the Clinic (2012-2015)

A project funded through the Foundation Fighting Blindness

Dr. Tsilfidis and her team have shown that a gene called XIAP can block retinal cell death in models of retinal disease.  Dr. Tsilfidis plans to use a novel gene therapy approach to slow cell death in many forms of retinal disease. XIAP gene therapy relies on a viral vector to transfer the XIAP gene into treated cells. Laboratory studies have demonstrated that this can protect the vision of experimental animals, whose retinas have been damaged by retinal detachment or genetic mutation. To inject human beings with a similar viral vector, the therapy must be manufactured according to strict standards and undergo rigorous testing. Viral vectors have previously been developed to deliver genetic material to retinal cells and have received FDA approval for other human clinical trials; Dr. William Hauswirth at the University of Florida has unparalleled expertise in this area. The Krembil Foundation, through The Foundation Fighting Blindness, is supporting the production of a viral vector produced in Dr. Hauswirth's facilities of a sufficient standard to gain regulatory approval for a human clinical trial in both Canada and the USA. This funding will also support some of the initial safety and toxicity testing necessary to start clinical trials using XIAP gene therapy.

Dr. Valerie Wallace

Toronto Western Research Institute

Investigating the Role of CCDC136 in Cone Function and Achromatopsia (2014-2017)

A project funded through the Foundation Fighting Blindness


​Achromatopsia is a genetic condition where patients experience a severe loss of vision in daylight, loss of colour vision and other vision disturbances.  Achromatopsia occurs because a genetic mutation prevents the cone photoreceptors in the retina from functioning properly. Similarly, cone dystrophy is also due to a loss of function in the cone photoreceptors associated with genetic factors.  All of the achromatopsia genes identified to date make proteins that are essential for cones to function and respond to light. One of the five known mutations can be identified in about 80% of people with achramatopsia, however in 20% of cases, the cause is unknown. Incidental to another study being conducted by Dr. Wallace, which focused on transplanting cone cells to restore sight, Dr. Wallace’s team identified a novel achromatopsia gene in mice. The team will work to understand and document the role of this gene, CCDC136, in cone cell function, and how its mutation leads to vision loss in mice. Dr. Wallace will also partner with Dr. Bernd Wissinger at the University Eye Clinic Tübingen. At this clinic, they have collected samples from 95 people who have achromatopsia where none of the known genes have been identified, as well as 47 people with cone dystrophy, due to unknown causes. The team will screen these samples to see if mutations in this gene cause disease in human patients.

Dr. Rod Bremner

Lunenfeld-Tanenbaum Research Institute

Strategies to Prevent and Treat Retinoblastoma Cancers (2012-2015)​


​The human retinoblastoma gene (RB) is part of a molecular pathway that is defective causing most human cancers.  Children missing one copy of the gene inevitably develop RB, and RB survivors have an increased likelihood of developing other cancers later in life.  Currently, there is no targeted treatment to prevent tumor development in these individuals.  Dr. Bremner and his team have developed genetic mouse models to mimic RB pathway defects.  These valuable research tools have helped them expose the molecular network that includes four critical protein nodes essential for RB initiation.  Dr. Bremner and his team will interfere, either genetically and/or pharmaceutically, with these nodes to prevent tumor formation.  The long term goal of these preclinical studies is to dramatically alter the management of cancer in patients with one defective copy of the RB gene.  ​ 

Dr. Kari Hoffman

​Centre for Vision Research, York University

Modulating Memory Circuits: Focal Deep Brain Stimulation treatments to Improve Medial Temporal Lobe Function (2014-2017)

A project funded in partnership with Brain Canada

Alzheimer’s disease is a devastating neurodegenerative disease with no effective treatment.  The memory deficits associated with the disease are the result of dysfunctional memory circuits in the brain.  Deep brain stimulation for the treatment of Alzheimer’s was recently pioneered by Dr. Andres Lozano, a fellow collaborator.  Deep brain stimulation (DBS) involves the targeted delivery of patterned electrical stimulation to specific regions of the brain to modulate circuit activity involved in memory.  The therapeutic mechanisms of deep brain stimulation for Alzheimers are largely unknown; understanding them would allow for more effective treatment.  Dr. Hoffman’s goal is to modulate memory networks in preclinical models using innovative, focal stimulation methods, to improve network function.  By systematically changing both the location, and timing of DBS, Dr. Hoffman and her team intend to refine and optimize the delivery of DBS to maximize its impact on improving memory function.  Ultimately these findings will impact DBS protocols for use in Alzheimer’s patients.

Dr. Ray Truant

McMaster University

Establishing a Fast Pipeline from High Content Screening to Pre-Clinical Compounds to Clinical Trials for Huntington's Disease (2014-2016)


Huntington’s disease is a devastating neurodegenerative disease.  Unlike other neurodegenerative diseases, the cause of Huntington’s is known: an expansion of CAG DNA in the huntingtin gene, resulting in a toxic mutant version of the huntingtin protein.  Part of this toxicity is because one end of the huntingtin protein is missing the attachment of a phosphate group which greatly impacts huntingtin shape and function.  The goal of Dr. Truant’s research is to identify compounds that can re-phosphorylate mutant huntingtin and recover protein function, which can then be developed into therapies for Huntington’s disease.  Dr. Truant has developed assays using high content microscopy and nanoscopy that can image the phosphorylation state and shape of huntingtin protein.  He is testing for small molecule compounds that restore the phosphorylation or the shape of mutant huntingtin in cell models of Huntington’s disease.  Successful compounds will then be used in mouse models of Huntington’s to test whether they can reverse the motor symptoms associated with Huntington’s disease.  By accelerating the pipeline to drug discovery, Dr. Truant’s goal is to rapidly identify novel drug candidates for Huntington’s disease that can be quickly brought to clinical trials.

Dr. Jeff Wrana

Lunenfeld-Tanenbaum Research Institute

Unraveling the Network Architecture of Cancer Cells (2012-2016)


Cancer is a disease associated with many mutations that combine together to allow cancerous cells to divide indefinitely.  Cancer cells are continually evolving and generating genetic diversity, which makes it difficult to develop targeted cancer treatment, and is the reason why cancer often evades therapy.  Dr. Wrana and his team believe the key to developing therapeutics that selectively target cancer cells is to understand how genes and proteins interact in large dynamic networks and how disturbances in these network interactions drive cancer formation and progression.  Using novel, cutting edge technology Dr. Wrana and his team of cancer and computational biologists will increase our understanding of how protein networks are assembled and how they contribute to cancer.  These findings will be crucial for exposing new targets for cancer treatments, and ultimately provide a foundation for the design and implementation of combinatorial strategies that improve the success of anti-cancer therapeutics.

* Not all grants have been displayed

Mechanisms of Disease

Past Grant:  The Role of Temporal Lobe Synchrony in Memory Formation (2013-2014)

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Past Grants:  Chemical Biological Approach to New Drug Leads for Huntington's Disease (2011-2012)

​                        Role of Cofilin Rods in Huntington's Disease (2009-2010)

Dr. Philippe Monnier

Toronto Western Research Institute

A New Strategy to Prevent Photoreceptor Degeneration (2015-2017)

A project funded through the Foundation Fighting Blindness​​


Within the eye, photoreceptor cells capture light making vision possible. In retinal degenerative diseases like retinitis pigmentosa, these cells die leading to vision loss.  Dr. Philippe Monnier studies what happens when nerve cells in the optic nerve are injured. Cells in the injured nerve receive protein signals that prompt the cell to die. If the cell’s outside surface is modified so that it ignores these signals, the cell is preserved.  In this research project, Dr. Monnier and his team will study this effect in a mouse model of retinitis pigmentosa. They will evaluate several ways of blocking these protein signals. One possibility involves an existing drug that may modify the outer surface of the photoreceptor to ignore the signals. If this approach proves promising, it could lead to important advances in retinal disease treatment.