Researchers from Généthon, 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. A first.

The work was published in the journal Nature Communications.

Duchenne muscular dystrophy is associated with abnormalities in the DMD gene, which encodes dystrophin, a protein that is essential for proper muscle function. This gene is one of the largest in our genome (2.3 million base pairs, of which over 11,000 are coding). Because of this size, it is technically impossible to insert the entire DNA for dystrophin into a viral vector (or even the 11,000 coding base pairs alone), as is usually done for gene therapy.

To meet this challenge, 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 side–effects 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 large–sized animal with this protein. Moreover, this innovative approach allows treatment of all patients with Duchenne muscular dystrophy, regardless of the genetic mutation responsible,” said Caroline Le Guiner, the main author of this study.