Background:
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder caused by mutations in the DMD gene, leading to dystrophin deficiency and progressive muscle degeneration. Recent advancements have introduced innovative therapies targeting genetic defects, pathophysiological pathways, and systemic complications, offering new hope for managing this debilitating condition.
Objectives:
This systematic review evaluates emerging therapies for DMD, focusing on their mechanisms of action, clinical outcomes, and potential to improve patient care. Key approaches include gene therapy, exon skipping, utrophin modulation, cell-based therapies, and anti-inflammatory agents.
Methods:
A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified relevant studies published up to 2024. Eligible studies included preclinical and clinical trials assessing novel DMD therapies. Data were synthesized qualitatively and quantitatively, adhering to PRISMA guidelines. Risk of bias was assessed using appropriate tools.
Results:
Analysis of 50 studies highlighted significant advancements. Gene therapies using adeno-associated viral (AAV) vectors restored 25%–40% dystrophin levels, improving motor function. Exon skipping therapies targeting exons 44, 45, and 51 restored 5%–15% dystrophin with functional gains. Utrophin modulation enhanced muscle stability in preclinical models. Cell-based therapies, including stem cell and induced pluripotent stem cell transplantation, showed potential for muscle regeneration but faced challenges in engraftment and immune response. Anti-inflammatory agents like vamorolone reduced fibrosis and inflammation with improved safety compared to traditional corticosteroids. Safety profiles across therapies were favorable, with mild-to-moderate adverse events reported.
Conclusion:
Emerging DMD therapies offer promising advancements, addressing the disease at multiple levels, from genetic correction to symptom modulation. These approaches could transform DMD management, improving patient outcomes and quality of life. Further research is needed to refine these therapies, address remaining challenges, and ensure long-term efficacy and safety.