Duchenne muscular dystrophy is the most common neuromuscular disease of children (affecting 1 boy in 3500-5000 births). It is caused by a genetic defect in the DMD gene residing on the X chromosome, which results in the absence of the dystrophin protein essential to the proper functioning of muscles.
The treatment being developed by researchers at Atlantic Gene Therapies, Généthon and the Institute of Myology, is based on the use of an AAV vector (Adeno Associated Virus) carrying a transgene for the skipping of a specific exon which allows functional dystrophin production in the muscle of the patient.
Safety, efficacy and stability of the treatment in dogs
In GRMD (Golden Retriever Muscular Dystrophy) dogs the treatment aimed at skipping exons 6, 7 and 8 of the dystrophin gene. The product was given by loco-regional administration in the forelegs of 18 dogs who were followed for 3.5 months after injection. It was well tolerated by all treated dogs; no immune response against the synthesized dystrophin was observed. Exon skipping resulted in high levels of expression of dystrophin in the treated muscles. The results of this treatment also indicate that, once injected into the muscle tissue a prolonged and stable effect is produced over the observation time of the study and, unlike antisense oligonucleotides already used clinically for exon skipping, it does not need to be re- administered regularly. The synthesis of "new" dystrophin is dependent on the dose of vector injected: the higher the dose, the greater the exon skipping is effective. Muscle strength also increases with dose. 80% of muscle fibers expressed the "new" dystrophin at the highest dose. This is a very encouraging result because a minimum of 40% of dystrophin in muscle fibers is believed to be necessary for the muscle force to be significantly improved.
A phase I/II clinical trial phase
These results open the way for a phase I / II clinical trial by loco-regional administration in the upper limb of non-ambulatory Duchenne muscular dystrophy patients which are amenable to treatment by the specific skipping of exon 53. The regulatory toxicology and biodistribution studies have just ended and the filing of an application with regulatory authorities is planned for 2015.
Source: AFM-Téléthon