Self-Assessment: Toxic Myopathies & Neuropathies | Advances in Duchenne Treatment & Management-Dr. McDonald Presentation

Dr. McDonald Presentation

Pdf Summary

Duchenne Muscular Dystrophy (DMD) is an X-linked, progressive, and fatal disorder primarily affecting boys and young men, characterized by the lack of functional dystrophin protein. Dystrophin serves as a crucial linkage between muscle fiber contractile units and the extracellular matrix, defending muscle fibers against contraction-induced damage. Its absence leads to muscle fiber injury, degeneration, inflammation, fibrosis, and the loss of muscle function, progressing to paralysis, respiratory failure, cardiomyopathy, and premature death.<br /><br />Current therapeutic approaches target various aspects of DMD pathophysiology, including reducing inflammation and fibrosis, enhancing muscle mass and regeneration, correcting calcium handling issues, and addressing mitochondrial dysfunction. Glucocorticoids, such as prednisone and deflazacort, have been shown to delay loss of functional milestones. Novel therapies, including gene therapy, focus on replacing or restoring dystrophin.<br /><br />Gene therapy for DMD involves three strategies: gene editing to repair defective genes, gene transfer to add new genes, and gene silencing to prevent the expression of harmful genes. Among the promising gene therapies is the investigational drug SRP-9001, which delivers a micro-dystrophin gene via an adeno-associated virus (AAV) vector. Preclinical and clinical studies have indicated its efficacy in improving muscle histology, reducing serum creatine kinase (CK) levels, and improving clinical outcomes as measured by the North Star Ambulatory Assessment (NSAA).<br /><br />Despite challenges, including variability in disease progression and treatment response, evidence suggests that SRP-9001 therapy can provide functional improvement in younger patients and stabilize function in older patients. The FDA granted accelerated approval for SRP-9001 for 4-5 year-olds in June 2023.<br /><br />The clinical landscape continues to evolve with ongoing studies and combination treatments seeking to further improve outcomes for DMD patients. The multidisciplinary efforts at institutions like UC Davis underscore the critical role of research, clinical trials, and comprehensive patient care in advancing therapies for DMD.

Keywords

Duchenne Muscular Dystrophy

DMD

duchenne

dystrophin

gene therapy

SRP-9001

glucocorticoids

muscle degeneration

clinical trials

FDA approval

UC Davis

duchenne

DMD