Duchenne Muscular Dystrophy: from Dystrophin Deficiency to Emerging Therapeutic Strategies
TL;DR
DMD is a severe, progressive X-linked recessive neuromuscular disorder caused by pathogenic mutations in the DMD gene, resulting in deficiency or absence of the dystrophin protein, and multidisciplinary management has improved survival and quality of life.
Abstract
: Duchenne Muscular Dystrophy (DMD) is a severe, progressive X-linked recessive neuromuscular disorder caused by pathogenic mutations in the DMD gene, resulting in deficiency or absence of the dystrophin protein. It predominantly affects males and is characterized by progressive skeletal muscle weakness, delayed motor milestones, Gowers’ sign, calf pseudohypertrophy, and gradual loss of ambulation. Dystrophin deficiency destabilizes the muscle membrane, leading to repeated muscle fiber damage, calcium influx, oxidative stress, chronic inflammation, and replacement of muscle tissue with fibrotic and fatty tissue. Respiratory muscle weakness and cardiomyopathy are major complications and remain important causes of mortality. Diagnosis primarily involves markedly elevated serum creatine kinase followed by genetic testing, while muscle biopsy, electromyography, and cardiac and respiratory assessments may support diagnosis and disease monitoring. There is currently no definitive cure; however, multidisciplinary management has improved survival and quality of life. Corticosteroids such as prednisone, prednisolone, deflazacort, and newer therapies such as vamorolone help slow disease progression. Mutation-specific exon-skipping therapies, gene replacement therapy, and emerging targeted treatments have expanded therapeutic options for eligible patients. Physiotherapy, respiratory support, cardiac management, occupational therapy, and nutritional and psychosocial care are also essential components of treatment. Pharmacists play an important role in medication management, monitoring adverse effects, counselling, adherence, drug-interaction screening, and supporting the safe use of corticosteroid and newer targeted therapies. This review summarizes the epidemiology, etiology, genetics, pathophysiology, clinical manifestations, diagnosis, disease progression, pharmacological and non-pharmacological management, and role of pharmacists in DMD care.