CAP-1902 Enhances Muscle Function in mdx Mice


Pre-Clinical Research

Poster Number: S31


Kevin Gaffney, PhD, Capacity Bio, Karel Erion, PhD, Capacity Bio, Kathleen Rodgers, PhD, University of Arizona

Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by mutations in the dystrophin gene. Lack of dystrophin causes microtears in muscle that leads to calcium overload and subsequent mitochondrial dysfunction, which contributes to the chronic inflammatory state and muscle degeneration that characterizes DMD patients. Addressing the mitochondrial dysfunction in DMD is an attractive target to modulate pathology, either as a standalone therapy or combined with dystrophin-based therapies. Mitophagy is the process by which cells tag, remove, and replace dysfunctional mitochondria. Capacity Bio has discovered the first cell-surface GPCR that activates mitophagy when agonized. The goal of these studies was to determine the effect of activating this receptor using a small molecule, CAP-1902. CAP-1902 treatment significantly and dose-dependently enhanced in vivo muscle function and prevented eccentric injury induced force loss. Improvements in muscle histology including a reduction in fibrosis, necrosis and degenerating fibers was also observed. Circulating inflammatory biomarkers were significantly decreased and anti-inflammatory markers were increased following treatment with CAP-1902. Activation of mitophagy may serve as a novel therapeutic option for DMD patients to improve muscle function.