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25 Jul 2017

Gene therapy: Microdystrophin restores muscle strength in Duchenne muscular dystrophy

Illustration for article: Gene therapy: Microdystrophin restores muscle strength in Duchenne muscular dystrophy

Researchers from Genethon, the AFM-Téléthon laboratory, Inserm (UMR 1089, Nantes) and the University of London (Royal Holloway) demonstrated the efficacy of an innovative gene therapy in the treatment of Duchenne muscular dystrophy. Indeed, after injecting microdystrophin (a “shortened” version of the dystrophin gene) via a drug vector, the researchers managed to restore muscle strength and stabilise the clinical symptoms in dogs naturally affected by Duchenne muscular dystrophy. This work published in Nature Communications has been achieved thanks to the donations of the French Téléthon.

Teams at Genethon developed, in collaboration with a team at Royal Holloway University of London led by Pr. Dickson, and produced, a gene therapy drug combining an AAV-type viral vector with a shortened version of the dystrophin gene (approximately 4,000 base pairs), allowing the production of a functional protein. Dr Le Guiner’s team tested this innovative treatment in 12 dogs naturally affected by Duchenne muscular dystrophy. By injecting this microdystrophin intravenously, and hence into the whole body of the dogs, the researchers observed that dystrophin expression returned to a high level, and muscle function was significantly restored, with stabilisation of the clinical symptoms observed for over 2 years following injection of the drug. No immunosuppressive treatment was administered beforehand, and no sideeffects were observed.

Some Golden Retrievers develop Duchenne muscular dystrophy naturally. The successful treatment of these dogs, which show the same clinical symptoms as children with this disease, and are of a similar weight, is a decisive step toward developing the same treatment in children. “This preclinical study demonstrates the safety and efficacy of microdystrophin, and makes it possible to consider developing a clinical trial in patients. Indeed, this is the first time that it has been possible to treat the whole body of a largesized animal with this protein. Moreover, this innovative approach allows treatment of all patients with Duchenne muscular dystrophy, regardless of the genetic mutation responsible,” says Caroline Le Guiner, the main author of this study.