Project 453323

Myotonic dystrophy type 1 (DM1) is a genetically inherited disease, characterized by progressive dysfunction of multiple organs. While DM1 affects many body functions, including the heart, lungs and gastrointestinal system, the most common symptoms of DM1 occurs within skeletal muscle. Individuals with DM1 suffer from muscle weakness (myopathy), wasting (atrophy), function (myotonia), and poor mobility. Typically, the earlier the symptoms appear during the life span, the more devastating the loss of muscle function will be. DM1 occurs in ~1 in 2100 births, making it a very prevalent genetic disease - this rate of occurrence is even higher in specific regions in Canada. Despite the prevalence of DM1 in Canada, there is no cure, no current recommended treatment options. Strategies for the maintenance of muscle function are desperately needed in this clinical population. While many promising therapies have been proposed over the last ~30 years, these have not materialized into meaningful therapies for patients. Though most common clinical signs of DM1 are related to muscle weakness and muscle wasting, there has been little examination of one of best ways to reverse these effects in muscle regardless of age or disease - exercise. Astoundingly, there are no studies examining the molecular and cellular mechanisms by which exercise may benefit patients with DM1. Here, we propose to undertake the first comprehensive examination of skeletal muscle health in male and female patients with DM1 in the context of exercise. These examinations will include clinical outcomes such as muscle function, strength, and coordination but will also include underlying genetic, metabolic, and muscle regenerative capacity as well. Subsequently, we will examine whether skeletal muscle health, and the underlying factors, can be improved with chronic exercise training in this clinical population.