Daniel Michele, associate professor in the department of molecular and integrative physiology at the University of Michigan in Ann Arbor, was awarded an MDA research grant totaling $364,965 over three years to study the underlying mechanisms of muscle weakness and muscle fatigue in Duchenne (DMD) and Becker (BMD) muscular dystrophies. Michele's work could have implications for other dystrophies as well, including limb-girdle muscular dystrophy (LGMD) and congenital muscular dystrophy (CMD).
"Recent work by a number of laboratories has shown that patients and mouse models with DMD show early muscle fatigue, particularly when muscles are active, such as during exercise," Michele explains. "This early fatigue is thought to be primarily due to disruption of the production of nitric oxide in muscle, which helps dilate blood vessels in muscle and increase blood flow during exercise."
Michele notes that there are several forms of the enzymes that produce nitric oxide in muscle, and "it's not exactly clear how nitric oxide production is regulated in muscle during exercise and exactly what causes dysfunction in muscular dystrophy."
With colleagues, Michele is working to determine how nitric oxide production is regulated in muscle and if the normal regulators of nitric oxide production can be targeted to improve muscle blood flow and reduce muscle fatigue during exercise. The team will work primarily with the mdx mouse model (a DMD research model), but also will look at mouse models of other forms of genetic muscular dystrophy and muscle injury.
"Overall, we hope to show that manipulation of the regulators of nitric oxide production will provide potential therapeutic benefit to prevent muscle fatigue," Michele says.
Funding for this MDA grant began Aug. 1, 2012.