Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the neuromuscular system resulting in paralysis and ultimately death. Currently, no effective therapy is prescribed for patients; however, several therapeutic strategies are showing promise. Either exercise or treatment with adeno-associated virus/insulin-like growth factor-1 alone has therapeutic benefits in an amyotrophic lateral sclerosis transgenic mouse model. We show here that activity duration affects the therapeutic benefit associated with exercise, with 6- and 12-hour exposure to a running wheel providing significant motor function benefits and increased survival. Remarkably, a combination of insulin-like growth factor-1 gene delivery and exercise has profound effects on survival and function, indicative of synergistic effects with exercise and insulin-like growth factor-1. Our results indicate that a drug treatment in combination with appropriate exercise may provide the most promising therapy for amyotrophic lateral sclerosis to date.