Stage-specific Therapy for Muscular Dystrophies: From Care Standards to Gene and RNA Medicines

Muscular dystrophies (MDs) are genetic disorders marked by progressive myofibre loss, impaired regeneration and weakness that eventually involves cardiac and respiratory muscle. Multidisciplinary care has extended survival, and gene- and ribonucleic acid (RNA)-directed therapies now address the underlying molecular lesions. We propose a stage-specific framework that matches therapeutic modality to mechanism, disease stage and organ burden and identify the practical barriers to translating gene- and RNA-targeted therapies into routine care. We reviewed pivotal clinical trials, regulatory decisions, care guidelines and mechanism-defining studies across Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, myotonic dystrophies (DM1/DM2) and selected congenital forms, prioritising modality-to-mechanism fit over exhaustive cataloguing. DMD has led the field, with exon-skipping oligonucleotides and adeno-associated virus micro-dystrophin gene transfer approved in some jurisdictions. Benefit is nonetheless constrained in advanced disease and in cardiac and diaphragmatic rescue, and depends on early initiation, immune compatibility and demonstrable functional gain. Other dystrophies require different logic, such as suppression of toxic RNA or aberrant transcription, or control of inflammation and fibrosis. No single modality serves every patient or every stage. The most practical way forward combines exemplary multidisciplinary care with mechanism-matched intervention delivered at the right time, supported by decision-linked biomarkers and safer, more equitable long-term access.