Grant: DRA: Canada Impact+ Research Training Awards - Doctoral

"In simplest terms, neurodegeneration is a highly complex disease with a high unmet medical need that affects multiple biochemical pathways and has no known singular cause. Oxidative stress, however, is implicated as a central player in the progression of neurodegeneration and has been found to be a key hallmark of many diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, Parkinson’s, and other neurodegenerative motor neuron diseases. To date, few treatments have been developed that halt neurodegeneration, with current drugs having limited success. For instance, only 2 FDA-approved drugs, Edaravone, an antioxidant, and Riluzole, an antiglutamatergic, are widely used clinically for ALS, and possess only modest clinical benefits with new drugs urgently needed. Using a trifunctional boron-based drug design strategy that selectively targets oxidative stress, the Tranmer research group has developed a small molecule therapeutic called Borsantrazole™ (BSZ) and evaluated BSZ in cell-based experiments, toxicity models, and the SOD1-G37R ALS animal model. Borsantrazole™ has been found to be safe and efficacious in animal studies, and generated superior results to currently approved ALS drugs in ALS mouse models, in terms of increasing survival, reducing ALS-associated weight loss and slowing the onset of the disease. Borsantrazole™ has been shown to target oxidative stress selectively, and is proposed to mitigate neurodegeneration through limiting the amount of reactive oxygen species that cause neurodegeneration. The proposed research will build upon current successes in ALS and explore the ability of Borsantrazole™ to reduce neurodegeneration in other models of ALS and Alzheimer’s, Parkinson’s, and other neurodegenerative motor neuron diseases. "