Therapeutic Advances in Duchenne Muscular Dystrophy: Regulatory Milestones, Emerging Modalities, and Implications for Clinical Practice

Abstract

Duchenne muscular dystrophy (DMD) is undergoing rapid therapeutic change, driven by mutation-specific treatments, gene-based interventions, and non-gene disease-modifying approaches. At the same time, regulatory decisions and emerging safety data increasingly determine which therapies can be used, in which patients, and under what monitoring conditions. This review provides a clinically focused synthesis of approved and late-stage therapies, including corticosteroids and the dissociative steroid vamorolone, exon-skipping antisense oligonucleotides, the histone deacetylase inhibitor givinostat, and systemic micro-dystrophin gene therapy, while distinguishing these options from earlier investigational platforms. Recent milestones, including divergent United States and European decisions on micro-dystrophin gene therapy, safety-driven label restrictions after fatal acute liver injury, discontinuation of the investigational gene therapy fordadistrogene movaparvovec after trial failure, and non-renewal and subsequent withdrawal of the nonsense-mutation read-through agent ataluren, show that regulatory interpretation now directly shapes therapy availability. Pending decisions on cardiac-directed cell therapy and a conjugate-based exon 51 agent may further alter clinical practice in the near term. Emerging approaches focused on tissue delivery, durability, and cardiac involvement, together with non-gene strategies targeting inflammation, fibrosis, contractility, and cardiomyopathy, are moving DMD management toward stage-based, combination-oriented care guided by molecular diagnosis, disease stage, safety considerations, and regional regulatory context.