Keys to understanding the risk of post-gene therapy myositis in DMD

The teams responsible for developing a gene therapy (GT) mediated by a recombinant adenovirus-associate for Duchenne muscular dystrophy (DMD), delandistrogene moxeparvovec (a gene therapy authorised in the United States under the name Elevidys®), are reporting the results of immunological studies carried out following the occurrence of undesirable side-effects:

• two cases of severe myositis occurred in sick children included in the ENDEAVOR protocol aimed at having the muscle produce microdystrophin,
• the study of the immune response linked to T lymphocytesC’est une catégorie de globules blancs. Ces petites cellules au noyau arrondi et volumineux sont impliquées dans les aspects spécifiques des réactions immunitaires. Il existe deux catégories de lymphocytes les lymphocytes B (qui secrètent les anticorps) et les lymphocytes T. in these patients demonstrated that exons 8 and 9 of the microdystrophin transgene were immunogenic.

On the basis of these results, the authors recommend excluding DMD patients with an anomaly in exons 8 and 9, which would put them at risk of developing highly deleterious immune reactions.

Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy. Potter RA, Moeller IH, Khan S et al. Sci Rep. 2025 Jan.