Exercise Adds to the Beneficial Effect of Gene Therapy in ALS Mice

October 24, 2004

Investigator Brian Kaspar, Ph.D. reported on October 24  that simply exercising adds to the benefit from the high technology approach of gene therapy, in a mouse model of ALS. Even adding exercise after the disease has appeared extends survival of SOD1 mutant mice, Kaspar said in a talk at the meeting of the Society for Neuroscience in San Diego.

Future clinical trials should consider optimal physical activity for maximal therapeutic potential in ALS, said Kaspar, of the Columbus Children's Research Institute at The Ohio State University.

The effect of exercise in ALS has been controversial, Kaspar acknowledged. Varsity athletes were reported to have increased incidence of the disorder. The mice he works with have had free access to a running wheel. But they are not forced to exercise, and that could make a difference. We plan to force exercise, and we expect that to hasten the progression of disease, Kaspar said.

While the data are exciting, further work needs to test what level of exercise might be beneficial. ALSA Science Director Lucie Bruijn cautioned that exercise could prove detrimental for people with ALS. Studies to clarify the issue of exercise in ALS are planned. ALSA is co-funding entry of IGF1 into clinical testing, together with Ceregene, a San Diego company.   A trial is expected to begin in early 2005.

Patients should always check with their doctors about adding any exercise to their treatment plan.

Kaspar and colleagues at the Salk Institute and at Johns Hopkins University have been testing gene therapies that deliver nutrient factors to nerves. The viral vector carrying the therapeutic gene is injected into muscle, and the nerve endings take up and transport the factors back into the motor neurons in the spinal cord. By this approach, both Insulin growth factor (IGF1) and glial derived neurotrophic factor (GDNF) can increase survival of SOD1 mutant mice. For example, IGF1 boosts survival by 20 days, the largest extension of lifespan so far in this mouse, said Kaspar, when delivered at the time of overt disease.

When wheel running is added early in the disease onset, and combined with the IGF treatment, mice live up to 202 days, a significan extension of survival, said Kaspar. Motor performance as measured by rotarod testing also improves with the combined strategy. These animals can perform motor function tests for much longer, he said.

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