Centre for Research on Biomolecular Interactions presents Prof. Christopher Perry, Faculty of Health in the school of Kinesiology and Health sciences, York University

Talk: Pre-clinical development of mitochondrial therapeutics for treating muscle weakness in Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy causes progressive muscle weakness leading to immobility, respiratory insufficiency, and cardiac dysfunctions. There is no cure for this genetic disease, leaving treatment of secondary contributions as the current approach for therapy. While glucocorticoids are the mainstay for treating inflammation, there remains a loss of mobility, functional independence and reduced lifespan that underscores the urgent need for developing new strategies that target other secondary complications. A promising prospect is to restore healthy function of mitochondria – the ‘powerhouse’ of muscle cells that provide the energy necessary for muscle strength and endurance. While the disease stems from mutations in the gene encoding dystrophin – a protein that connects and stabilizes the cell membrane and cytoskeleton - we and others have demonstrated that mitochondrial ATP synthesis is also impaired in this disease concurrent with elevations in mitochondrial reactive oxygen species emission (hydrogen peroxide). In this light, the emergence of ‘mitochondrial-targeted compounds’ opens a new direction for therapy development. As an example, our partnership with Stealth Biotherapeutics Inc. demonstrates that the cardiolipin-targeting peptide SBT-20 improves specific aspects of limb muscle and diaphragm function or histopathology in a mouse model of Duchenne muscular dystrophy while improving the ability of mitochondria to produce ATP with lower rates of hydrogen peroxide emission. The heterogenous responses between muscles raises new questions regarding the complex relationship between mitochondria and muscle dysfunction that may guide further development of mitochondrial therapeutics for this disease as well as other neuromuscular disorders.

Date: Wednesday January 13,2021

Time: 2:00pm-3:00pm