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

Abstract

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. Ann Neurol 2005