Grant: Operating Grant

Mitochondria are the most important source of energy generation in muscle cells. In this grant, we propose that impaired mitochondrial function plays a major role in Duchenne muscular dystrophy (DMD). Our goal is to determine if mitochondrial function and overall skeletal muscle health can be improved in mdx mice (model of DMD). The treatment methods will consist of drug therapies, gene therapy, and muscle training exercises. We believe that these treatments are promising because our recently published data indicate better mitochondrial function in the hearts of mdx mice after 6 weeks of treatment with the drug sildenafil (Viagra). In previous studies, improved mitochondrial function has been found in mdx mouse diaphragm muscle after a similar period of muscle training. We will now determine whether these treatments, applied either alone or together, are able to improve abnormal calcium levels, oxidative stress, inflammation, and ultimately muscle strength. Considering the major advantages of pharmacological and training therapies in terms of safety and relative ease of clinical application, these treatments could significantly improve quality of life for DMD patients.