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.
Kaspar
Brian K
BK
The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Frost
Lindsay M
LM
Christian
Lindsey
L
Umapathi
Priya
P
Gage
Fred H
FH
D000375:Aging / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002452:Cell Count; D000229:Dependovirus / Q000235:genetics; D005081:Exercise Therapy; D015870:Gene Expression; D015316:Genetic Therapy; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008136:Longevity; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D004856:Postural Balance / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012420:Running; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016019:Survival Analysis
C000606290:SOD1 protein, human; D012313:RNA; D007334:Insulin-Like Growth Factor I; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1