Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Alzheimer's disease (AD) affects over half a million Canadians. AD is characterized by a gradual decline in cognition, which arises in response to several pathological changes in the brain including degeneration and dysfunction of nerve cells. At present, there is a critical need for AD therapies that enhance neuronal survival and function. Neurotrophins are proteins in the brain that induce neuronal survival and function, and can potentially halt cell loss observed in AD. In particular, nerve growth factor (NGF) has significant potential for the treatment of AD. The main challenges in clinical trials for NGF have been delivery to the brain in sufficient doses to impact cell function and controlling its delivery to specific brain areas to minimize off-target effects. Novel therapeutic agents with more favorable pharmacological properties than native NGF have been developed to address these limitations. These molecules are classified as tropomyosin receptor kinase A (TrkA) agonists which stimulate neuronal survival and activity by interacting with TrkA present on neurons. Moreover, a promising strategy for the non-invasive delivery of therapeutics to specific brain areas is magnetic resonance imaging-guided focused ultrasound (MRIgFUS) combined with microbubbles given intravenously. The interaction of ultrasound with circulating microbubbles allows for drugs injected intravenously to enter the brain at MRIgFUS-targeted areas. In this project, we will use animal models to establish the efficacy of TrkA agonists delivered to the brain using MRIgFUS. We expect that this treatment will improve neuronal health and cognition, while minimizing side effects. Overall, this research will provide key milestones in animal models prior to clinical translation for AD patients.