OBJECTIVES: DMD is a rare genetic disease characterized by progressive muscle degeneration caused by mutations in the dystrophin protein, which aids in maintaining muscle cells. Recently, gene therapy for neuromuscular disease has made substantial progress with AAV vectors as they are not linked with any pathogenicity, have low immunogenicity, and can maintain transgene expression in non-dividing cells for years. In this review, the efficacy and safety of AAV vector mediated gene therapy for DMD is highlighted.

METHODS: Systematic literature search was conducted from database inception to December 2021 in EMBASE, MEDLINE, CDSR, and DARE databases. Two independent reviewers conducted abstract and full text screening.

RESULTS: This SLR identified 6 publications (one journal article and five conference abstracts) reporting results from two unique therapies SGT-001 and rAAVrh74.MHCK7. micro-dystrophin (SRP-9001). Published findings from the IGNITE DMD phase I/II clinical trial of SGT-001 in adolescents and children suggested that untreated controls had a 10.7% mean decline in predicted forced vital capacity, compared to 3.9% improvement in low-dose participants and 16.7% improvement in high-dose participants in lung function. One-year functional and quality of life assessments also showed positive improvements. All post-dosing serious adverse events (AEs) were resolved. In an open-label, phase I/IIa nonrandomized trial of rAAVrh74.MHCK7.micro-dystrophin, all patients had proven vector transduction, functional improvement of North Star Ambulatory Assessment (NSAA) scores, and lower creatine kinase levels (post-treatment vs. baseline) over a 1-year period. Similarly, in part 1 of a three-part multicenter phase II randomized trial, children aged 4–5 years exhibited a statistically significant difference on NSAA change between rAAVrh74.MHCK7.micro-dystrophin and placebo groups (+2.5, p=0.0172). Treatment-related AEs were transient and manageable.

CONCLUSIONS: Currently, clinical trials for gene transfer therapies in DMD patients are in phase I or II. Preliminary results suggest that these therapies are efficient, safe, and well tolerated.