Impact and Interplay of Corticosteroid Regimen and Exercise Training on DMD Muscle Function
Abstract
Duchenne Muscular Dystrophy (DMD) is a devastating, genetic neuromuscular disease affecting approximately 1 in 3,500 boys, causing loss of muscle function, early loss of ambulation and death generally by their late twenties. Currently there is no cure, with the search for effective therapies a major area of research focus. The overall goal of this exciting project is to test two new therapeutic strategies for patients with DMD: a new low-dose weekend regimen of corticosteroids; and a comprehensive exercise training program involving the lower extremities. While steroids are at present the only available treatment to maintain ambulation for up to 2 years, there are serious side effects associated with taking steroids daily over a long term, including weight gain and behavioral disturbances, resulting in a pressing need to find alternate steroid dosing strategies. Interestingly, recent work in mice shows that taking a daily steroid dose only on the weekend is equally effective as daily dosing, with the suggestion that it may result in fewer side effects. One focus of this current study is to test this new strategy in young boys with DMD, to determine if there are fewer weight gain and behavioral issues after 1 year of treatment with low-dose weekend steroids compared to boys who take steroids every day. Exercise training, which is well known to improve muscle function and physical abilities in healthy individuals, is increasingly being considered for DMD. Overall, the neuromuscular community has been cautious in its approach to exercise, with doctors often advising patients to avoid exercise due to fears of increasing muscle damage. While high intensity exercise is known to be damaging, there is increasing evidence that lower intensity exercise (such as riding a stationary bicycle) may be beneficial to boys with DMD and may delay progression of their disease. However, there is very little information in the literature about the dose of exercise (type, intensity, frequency) that may be beneficial for boys with DMD. We have recently tested a moderate intensity strength training program involving the legs in boys with DMD, with our preliminary results showing that not only was the exercise program not damaging, but it improved the muscle strength and ability to go up and down stairs in a small group of boys with DMD. Because most doctors recommend that boys with DMD take steroids, it is important to also understand how exercise interacts with steroid therapy, and importantly, whether exercise can add further benefit to boys taking low dose weekend steroids. The second focus of this study is therefore to determine whether a new exercise training program (combining cycling and leg strengthening exercises) helps to improve muscle function and physical ability in boys with DMD, and whether this combination of therapeutic strategies can help prevent the progression of disease within muscle by causing beneficial adaptations making the muscle stronger and less fatigable. In order to ensure safe and effective exercise training, the researchers have teamed up with engineers to design the Therex-DMD, a new device allowing for therapeutic exercise in boys with DMD, which will be used in the home setting with live video monitoring of exercise sessions by the research team. Our experimental approach will rely on our expertise of non-invasive assessment of muscle through magnetic resonance imaging, and experience in working with boys with DMD over the past several years. This project directly addresses the Focus Areas described in this funding opportunity, namely novel interventions designed to improve care and quality of life due to their impact on skeletal muscle in boys with DMD. In the short term (3 years), we will gain new information as to whether weekend steroid dosing is an effective alternate strategy to daily dosing (but with fewer side effects), and whether the exercise program and Therex-DMD device can improve muscle stren
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910330
Entities
People
- Tanja Taivassalo
Organizations
- United States Army
- University of Florida