Grant: Fellowship: Canada Impact+ Research Training Awards - Postdoctoral

"Amyotrophic lateral sclerosis (ALS) destroys motor neurons controlling movement, leaving patients unable to walk, speak, or breathe, with survival of only 2–5 years post-diagnosis. ALS is exceptionally difficult to treat because only 10% of cases have a known genetic cause; the remaining 90% result from complex interactions between genes, environment, aging, and lifestyle. Current ALS treatments modestly slow disease progression and cannot rebuild the neural circuits required for movement. My goal is to develop a gene therapy targeting early disease mechanisms in the motor cortex, where ALS dysfunction begins and drives progression. I will use a carefully engineered virus to safely deliver a customized gene that activates a natural neuronal identity program and strengthens cellular resilience. This approach targets a triple therapeutic opportunity. First, it converts astrocytes, support cells that normally protect neurons but become proliferative and toxic in ALS, into new, functional neurons. Second, it reduces the number of these harmful astrocytes that worsen disease. Third, it strengthens surviving neurons to better resist the cellular stress that causes degeneration. In preliminary studies using ALS mouse models, this approach improved neuronal survival, motor function, and lifespan. My proposed work will use an ALS mouse model to refine this strategy by testing interventions at both early and late disease stages and defining the underlying mechanisms. By combining early intervention, neuronal replacement, and enhanced resilience of surviving neurons, this project represents a fundamentally new approach to ALS therapy. For patients facing this relentless disease, this could shift the goal from slowing decline to genuinely restoring what has been lost."