Effects Of Different Exercise Regimen On The Disease Phenotype In Mdx Mouse Model Of DMD: 2697 Board #217 June 2 11

PURPOSE: Effects of exercise on the disease phenotype in neuromuscular disease mouse models is not systematically evaluated. Therefore, we have designed a preclinical trial in the mdx mouse model of Duchenne muscular dystrophy to specifically investigate the effects of forced downhill and horizontal treadmill exercise as well as voluntary wheel exercise. We assessed effects of exercise intervention on the muscle function and pathology using a comprehensive set of phenotyping measures. METHODS: This study involved a group of 12 week old wild-type BL10 (dystrophin sufficient) mice and a group of mdx (dystrophin deficient) mice. Each group was divided into 4 exercise regimen groups (n=5): No exercise, downhill treatment (DT), horizontal treatment (HT), and voluntary wheel exercise (VW). The groups were subjected to exercise 3x per week for 13 weeks. Skeletal muscle function (grip strength) was evaluated at 12, 17, and 25 weeks of age and cardiac function was evaluated using echocardiography at 25 weeks of age. RESULTS: Exercise intervention did not show a change in bodyweights of the BL10 mice. However, these mice showed significant improvement in hindlimb (HL) but not forelimb (FL) grip strength in comparison to non-exercised group. Analysis of the serum showed that the creatine kinase (CK) levels in the VW group significantly increased compared to the non-treated group. All three exercise interventions showed significant decreases in body weight at 25wks of age of mdx mice. Dystrophin deficient mdx mice showed different effects on muscle function depending on the exercise regimen. DT exercise was significantly detrimental to HL grip strength, while VW exercise showed significant improvement on HL grip strength over time. Evaluation of cardiac function (% ejection fraction and fraction shortening) showed that HT and VW but not DT interventions showed significant improvement. Analysis of CK levels showed that the VW group significantly increased compared to the non-treated group. CONCLUSIONS: Our study demonstrates that type of exercise intervention significantly affects dystrophin deficient skeletal and cardiac muscle function. Our study highlights that mild but not strenuous (DH) exercise regimen show benefits in DMD muscle therefore caution must be taken when prescribing exercise regimes to DMD patients.