Safety and efficacy of AAV-based mini- and micro-dystrophin gene therapies in Duchenne muscular dystrophy: a systematic review and meta-analysis of clinical trials.

DMD

AAV-mediated transfer of a mini- or micro-dystrophin intended to compensate for loss of DMD function

This PRISMA 2020 systematic review and meta-analysis, with a protocol prospectively registered on PROSPERO, searched five databases from inception to November 2025 to assess AAV-based mini- and micro-dystrophin gene therapies in Duchenne muscular dystrophy. Nine publications covering six trials (n = 218) were included, four contributing to the meta-analysis. Delandistrogene moxeparvovec improved NSAA scores by +3.08 points at one year (95% CI 1.85 to 4.32), with a greater effect in 4-5 year-olds (+4.06) than in 6-7 year-olds (+1.01); versus controls, only time to rise remained significant (−0.64 s), with no difference in NSAA or other timed tests. Fordadistrogene movaparvovec showed smaller effects. Most patients experienced treatment-related adverse events, mainly mild and transient, but serious events including hepatotoxicity and rare fatal outcomes occurred.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The number to remember is not the absolute NSAA gain but the age gradient: +4.06 points at 4-5 years versus +1.01 at 6-7 years, which shifts the question from whether to treat to when to treat, and makes diagnostic delay directly costly. The discrepancy between improvement from baseline and the absence of a difference versus controls on most endpoints should be presented to families as such, along with the reported hepatotoxicity and deaths. With 218 patients in total, precision remains low and the lack of long-term follow-up precludes any conclusion about durability.

Analysis by Dr Thibaut Benquey