Dystrophin restoration after AAV U7-mediated Dmd exon skipping is modulated by muscle exercise in a mouse model of severe DMD

A team of French researchers, involving researchers from the Institute, showed in a mouse model of severe DMD that voluntary exercise has an impact on a Dmd exon skipping approach and on muscle physiology.

D2-mdx mice were administered an AAV-U7 snRNA intra-muscularly to correct the Dmd reading frame and then allowed to run in a wheel for one month.

The results show that voluntary running :

  • did not induce muscle damage,
  • did not have a markedly negative effect on the exon skipping approach by AAV gene therapy, but somewhat decreased the restoration of dystrophin for reasons which are not yet well understood.

The authors conclude that exercise should be an additional element to be considered in the conception and design of future therapeutic approaches for DMD.

 

Monceau A, Moutachi D, Lemaitre M, Garcia L, Trollet C, Furling D, Klein A, Ferry A. Dystrophin Restoration after Adeno-Associated Virus U7-Mediated Dmd Exon Skipping Is Modulated by Muscular Exercise in the Severe D2-Mdx Duchenne Muscular Dystrophy Murine Model. Am J Pathol. 2022 Sep 13:S0002-9440(22)00279-6. doi: 10.1016/j.ajpath.2022.07.016. Epub ahead of print. PMID: 36113555.