Duchenne Muscular Dystrophy (DMD) is the most common neuromuscular disease in children, affecting approximately one in 3,500 boys at birth. It is caused by a mutation or deletion in the gene on the X-chromosome encoding dystrophin. The non-expression or the expression of very abnormal dystrophin makes the muscle fibers fragile, resulting in accelerated destruction of muscle tissue. This leads to general, progressive, irreversible and severe loss of muscle function. Between the ages of 10 and 13, sufferers become unable to walk and, by the time they reach adolescence, they require respiratory assistance. Survival can also be compromised by heart muscle involvement. Every year in France, 150 to 200 young boys are diagnosed with Duchenne muscular dystrophy.
Genethon is piloting a program based on the use of an Adeno-Associated Virus (AAV) vector carrying a transgene encoding microdystrophin together with the Institut de Myologie (Paris) and Professor George Dickson of the University of London (Royal Holloway).
Because of the very large size of the dystrophin gene (or DMD gene), it is technically impossible to insert the complete DNA of the gene into this type of vector.
The therapeutic strategy therefore consists of using a gene encoding a shortened but functional form of this protein (micro-dystrophin).
The production of this micro-dystrophin protein in the muscles of patients will make it possible to treat all patients affected with Duchenne muscular dystrophy.
In 2019, Genethon will launch a natural history study in two countries (France and UK) and three sites. The trial will recruit thirty patients and will enable the study of the profiles of the patients who will then be included in a phase I/II gene therapy trial, also scheduled to begin in 2019, with the product being manufactured by YposKesi.
For this program, Genethon has entered into a partnership agreement with Sarepta Therapeutics, a US-based biopharmaceutical company.