Grant: CIHR Fellowship

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of motor neurons in adults and is characterized by progressive muscular paralysis. Motor neurons are cells of the nervous system that innervate muscles to produce movement. Currently, there is no curative treatment for this fatal disease and patients with ALS have an average life expectancy of 3-4 years from the onset of symptoms. Global studies suggest that ALS has a death rate and incidence rate of 2 per 100,000 individuals annually. This suggests that each year approximately 700 people in Canada die of ALS and a further 700 are diagnosed with this disease. Multiple perturbations of cellular function contribute to the ALS disease state, one of which is the incorrect trafficking of cargo between different compartments of motor neurons. To date, Alsin and Spatacsin represent the only identified genetic risk factors mutated in ALS patients that function in the intracellular trafficking of cargo. In this study, I propose a multifaceted approach to functionally characterize the effects of ALS-associated mutations of Alsin and Spatacsin in motor neurons. This study will not only provide fundamental insight into the biological mechanism of Alsin- and Spatacsin-regulated cargo trafficking in normal and diseased motor neurons, but will also identify novel interacting partners of Alsin and Spatacsin that serve as potential therapeutic drug targets. Interestingly, the only approved treatment for ALS, Riluzole, although not of high efficacy, functions in part by regulating the trafficking of cargo in motor neurons.