Advancing Gene Therapies for Ultra-Rare Neuromuscular and Metabolic Diseases

Congenital Megaconial Muscular Dystrophy (MDCMC) is an ultra-rare, autosomal recessive neuromuscular disorder caused by pathogenic variants in the CHKB gene, which plays a critical role in phospholipid biosynthesis. A hallmark of CHKB muscular dystrophy is the megaconial phenotype, where enlarged, dysfunctional mitochondria accumulate at the periphery of muscle fibers. This reflects the profound impact of CHKB deficiency on lipid metabolism and cellular energetics, driving the degenerative progression of the condition.

Early motor symptoms frequently include hypotonia, poor head control, and delayed sitting, standing, or walking. Weakness initially appears in the posterior muscle compartments and gradually extends to anterior and medial groups. There is no cure for CHKB muscular dystrophy. Our preclinical gene therapy efficacy and tox studies in models of CHKB muscular dystrophy are supportive of our therapy being efficacious.