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. While monotherapies such as corticosteroids and exon-skipping agents have shown efficacy, combination therapies offer the potential to enhance therapeutic outcomes through synergistic effects.
Objectives:
This systematic review evaluates combination therapies for DMD, focusing on their efficacy, safety, and synergistic benefits in improving disease management.
Methods:
A comprehensive search of PubMed, Embase, and Cochrane Library identified studies published up to 2024 that assessed combination therapies in DMD. Eligible studies included preclinical and clinical research evaluating dual or multimodal treatments, such as corticosteroids combined with gene therapies, antisense oligonucleotides, or anti-inflammatory agents. Data were synthesized to identify therapeutic synergies and safety profiles.
Results:
Analysis of 20 studies revealed that combination therapies significantly improved functional outcomes compared to monotherapies. Corticosteroids combined with exon-skipping agents enhanced dystrophin restoration (mean increase: 15%–20%) and muscle strength. Pairing anti-inflammatory agents with gene therapies reduced fibrosis and inflammation while preserving functional gains. Safety profiles were favorable, with no significant increase in adverse events reported.
Conclusion:
Combination therapies in DMD demonstrate synergistic effects, improving both dystrophin restoration and functional outcomes while maintaining safety. These findings highlight the potential of integrated therapeutic strategies to address the multifaceted challenges of DMD and pave the way for more effective, personalized treatment approaches.