Context

CMT1A is a non-lethal, but heavily disabling orphan disease, starting mostly in children, teenagers, and young adults. CMT1A results from the loss of the myelin sheath, peripheral nerve degeneration and muscle waste, leading to foot drop symptom and hand/foot deformations. The most affected nerves are distal nerves such as fibular and tibial nerves (foot symptoms) and median nerves (hand symptoms). Today, this disease is still incurable and no pharmacological treatment is approved.

Benefits

Using Adeno-Associated Virus serotype 9 (AAV9), the most popular vector for gene therapy in the nervous system, the treatment reduces the expression of the protein responsible for the disease and prevents myelin loss, nerve degeneration and muscle waste. Briefly, the vector is administrated into specific upper and/or lower limb nerves (fibular, tibial and median) by a single interfascicular injection. This injection is performed transdermally with a minimally invasive medical device under echographic and electrophysiological controls. Contrary to local anesthetics, the AAV9 formulation is non-toxic. The injection occurs with small volumes (nanoliters) through multiple low pressure pulses (5 to 10 psi). Thus, the damage to nerve fibers is limited. In these conditions, the vector presents an extremelly high local transduction rate of the target cells, a large diffusion inside the nerve shaft and very limited spreading throughout the body.

Applications

Charcot-Marie-Tooth disease 1A (CMT1A)