RESPIRATORY TARGETED GENE THERAPY IN AN ALS MOUSE MODEL

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder that affects the upper and lower motor neurons resulting in muscle atrophy, paralysis, respiratory failure and death. 5-10% of ALS is familial and 20% of familial ALS overexpresses mutant SOD1. The ALS mouse model (the SOD1G93A mouse) overexpresses mutant SOD1 and recapitulates ALS pathophysiology making it an ideal model to study novel therapies for this disease. Using an adeno-associated viral vector (AAV) carrying a microRNA to knock down SOD1 (AAVrh10-H1-miRSOD1) we sought to correct the respiratory pathology in SOD1G93A mice with the goal of improving respiratory function and overall survival. A one time injection given at 60 days was able to extend survival of ALS mice and improve respiratory function