Enabling Skeletal Muscle Repair and Functional Recovery following Denervation-induced Injury Using Ultrasound Mediated Gene Delivery (UMGD)

Skeletal muscle is essential for mobility and its health relies upon innervation. Peripheral nerve injury denervates target skeletal muscle, causing immediate loss of function, atrophy, and development of fibrosis. Delayed re-innervation can result in permanent functional loss, leading to a myriad of physical, financial, social, and psychological burdens on affected individuals. Ultrasound-mediated Gene Delivery (UMGD) is a relatively novel technique that has been shown to provide localized and effective gene therapy in vivo. We hypothesize that UMGD of myogenic genes IGF-1, VEGF, and Ang-1 would sustain the mass and regenerative potential of denervated muscle awaiting reinnervation. After two weeks, UMGD of these genes mildly increased gross muscle weight, Type II fibre CSA, and vascularization compared to denervated muscle given no transgene. We have shown that UMGD is a viable model for targeted gene delivery to skeletal muscle through partial prevention of the atrophy and vascular loss induced by denervation injury. ; M.Sc.