Margaret Fahnestock, PhD and Maikel Rheinstadter, PhD

McMaster University

Project name: Delivering therapeutics across the blood brain barrier 

One of the major challenges in treating Alzheimer’s disease (AD) is the difficulty of delivering large therapeutic molecules into the brain due to the blood-brain barrier (BBB), which prevents entry of most molecules to the brain. To address this, Dr. Fahnestock and Dr. Rheinstadter are developing an innovative drug delivery system that uses empty red blood cells to transport large compounds across the BBB. The efficacy of this approach will be tested by: (1) injecting these carriers and their contents into mice to determine the optimal route, dose, and injection schedule to maximize the delivery of therapeutic proteins into the brain and (2) demonstrating that sufficient amounts of a protein important for brain function can be delivered to improve learning and memory in a mouse model of AD. If successful, this project will confirm the potential of red blood cells as an effective drug delivery system, paving the way for further development of this approach for AD and other neurodegenerative diseases of aging. 

Paul Fraser, PhD

University of Toronto

Project Name:Advancing a SUM02-based biologic for the treatment of neurodegenerative diseases 

Alzheimer’s disease (AD) is characterized by the accumulation of abnormal protein deposits, which causes nerve cell death leading to cognitive dysfunction in affected individuals. A key protein known as SUMO can attach to these proteins to counteract their effects. Dr. Fraser and his team have created a biological compound, SBT02, that replicates SUMO’s function, which has demonstrated potential in blocking the toxic effects of amyloid and reducing memory impairments in AD mouse models. Dr. Fraser will conduct extensive testing of SBT02 to determine the effective dose and frequency of administration in mice. If successful, this project will provide the necessary information to form the basis for a clinical trial.  

Martin Levesque, PhD

Université Laval

Project name: Advancing Neuroimaging Biomarkers for Parkinson’s Disease: Targeting Pathological Alpha-Synuclein with Immuno-Radioligand Imaging 

A hallmark of Parkinson’s disease (PD) is the aggregation of pathological alpha-synuclein (a-syn) proteins in the brain. The development of an a-syn-based imaging biomarker could improve the diagnosis and prognosis of PD. However, there are currently no clinically approved methods to image a-syn in human and therefore, there is an urgent need to develop methods to accurately image a-syn in the brain. Dr. Levesque will develop an antibody-based PET tracer that specifically binds to a-syn in the brain. If successful, the project will generate a novel imaging biomarker for PD, which can be further tested and validated in human studies. If proven safe and effective, this tool will address the critical need for improved diagnostic methods for PD and aid in identifying patients who may respond to a-syn-based therapies.   

Marco Prado, PhD

Western University

Project name: Testing the efficacy of an amyloid vaccine on high-level cognition in a new genetic-risk model of Alzheimer’s disease 

Recently developed Alzheimer’s Disease (AD) therapies help the immune system identify and clear amyloid from the brain, a core feature of AD. However, these treatments can cause side effects such as brain swelling and bleeding, which are worse in people that have the AD risk gene ApoE4. To address this, Dr. Prado’s team is testing a vaccine that selectively targets a soluble form of amyloid to prevent cognitive problems in mice without affecting the brain’s blood vessels. They will compare their vaccine with the currently available AD therapy, lecanemab, in a mouse model of AD with the ApoE4 risk factor and use sophisticated MRI and microscopy technology to study the brain.  The team will also use a touchscreen technology to measure any changes in cognitive function in real-time and as the mice age. If successful, this project will develop a therapeutic that avoids the harmful, sometimes fatal, effects seen in existing AD treatments. 

Joel Watts, PhD

University of Toronto    

Project name: Humanized mouse models targeting alpha-synuclein to improve drug discovery 

The use of animal models is critical for testing novel therapeutics to confirm safety and efficacy before moving to human trials. Therefore, there is an urgent need to develop “humanized” animal models that more closely mirror human disease. To facilitate development of therapeutics for Parkinson’s disease (PD), Dr. Watts will: (1) develop new mouse models of PD that express the human alpha-synuclein gene at normal levels in the brain, and (2) make these novel mouse models freely available to the research community. If successful, the project will produce a new mouse model that will better mirror human PD neuropathology and behavioural impairments. This model will help facilitate preclinical (i.e., animal) drug efficacy studies and fast-track translation of novel PD therapeutics for clinical use.