Duchenne Muscular Dystrophy

Overview

X-linked recessive progressive muscle-wasting disease caused by dystrophin gene mutations with 100% mortality from cardiac or diaphragm failure in late 20s-30s; Dyne Therapeutics' lead asset Dyne-251 targets exon 51 skipping. DMD is X-linked recessive, affecting boys, with diagnosis typically around age 4; by ages 8-10 patients can no longer rise from the floor, by ages 12-14 they are wheelchair-dependent, and death from cardiac or diaphragm failure occurs in the late 20s or 30s with 100% mortality. Dystrophin baseline in DMD exon 51 patients is approximately 0.4-0.5% of normal; Dyne-251 raised dystrophin to ~3% at 6 months and nearly 10% unadjusted (~20% muscle content-adjusted) at 12-24 months, exceeding any previously reported result for exon 51 skipping. (Segment 6 (25:00-30:00))