Genethon played a pioneering role in proving the potential of exon skipping as a way of developing innovative therapies for Duchenne Muscular Dystrophy (Goyenvalle et al., Journal Science 306, 2004). It has now embarked on an ambitious development project, which is currently in the preclinical stages, working in collaboration with the Institut de Myologie (Paris) and Genosafe (Evry).
The program is based on using an AAV (adeno-associated virus) vector carrying a transgene (U7) that allows the cellular machinery to skip over an exon 53 and produce ‘quasi-dystrophin’ in the patient’s muscle.
Locoregional intravenous administration of this therapy will make it possible to treat entire limbs and have demonstrated preclinical studies.
The toxicology and biodistribution regulations are currently in progress. The results will be critical to define the strategy for a future clinical trial. An application for a clinical trial should be submitted in 2015 to start the trial in 2016.
Duchenne Muscular Dystrophy (DMD) is the most common neuromuscular disease in child, affecting approximately one in every 3,500 male births. It is caused by mutations in the gene for dystrophin, which corresponds to a protein that has an extremely important role in muscle fiber integrity and function. It is characterized by general, progressive, irreversible and severe loss of muscle function. By about the age of 10 to 13, sufferers become unable to walk and, by the time they reach adolescence, they require respiratory assistance. Survival can also be threatened by heart muscle involvement.
Genethon has obtained ‘Orphan Drug’ status for this product from the European Medicines Agency (EMA).