Bioquímica do Exercício

Active Voice: Can Exercise Treat Duchenne Muscular Dystrophy?
By Robert W. Grange, Ph.D.

http://www.multibriefs.com/briefs/acsm/active3-29.htm

Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.

Robert W. Grange, Ph.D., is Associate Professor in the Department of Human Nutrition, Foods and Exercise at Virginia Tech. His research focus includes exercise and nutrition interventions as potential treatments for Duchenne Muscular Dystrophy. See the Jan. 2007 issue of ACSM’s Exercise and Sports Sciences Reviews (ESSR) for a related research review he coauthored, titled "Recommendations to Define Exercise Prescription for Duchenne Muscular Dystrophy.”

Duchenne Muscular Dystrophy (DMD) is a fatal skeletal-muscle-wasting disease that affects males from birth. It’s reasonable to believe that properly prescribed exercise could counter the “muscle wasting” effect by initiating positive muscle-building pathways. However, a logical argument against this line of thinking states that exercise could be more detrimental than beneficial, as the dystrophic muscles are susceptible to physical-activity-induced damage. From both practical and ethical perspectives, the foremost consideration is that we must do no harm to patients suffering from DMD. I have a deep appreciation for physicians, physical therapists and parents who strive to take the best care of their boys each day. It is easy, as a laboratory exercise physiologist who studies dystrophic mice and dogs, to overlook the serious responsibilities of these caregivers and the emotional connection they have with their boys. But I believe it is our role as exercise physiologists to be objective and to ask: Do we know whether exercise is or is not beneficial?

When I consider the potential role of exercise as a treatment for DMD, I recall arguments in the 1960s against exercise to treat cardiac patients. Some believed exercise would induce further heart damage and urged cardiac patients to avoid it. After many years of scientific inquiry, properly prescribed exercise has become a common treatment modality for cardiac rehabilitation. Although the disease mechanisms of DMD and heart disease are different, there has not been enough rigorous scientific inquiry to definitively state whether exercise is beneficial or detrimental to DMD. Although some practical recommendations are available, specific guidelines regarding exercise prescription (the type, frequency, and intensity of exercise) are lacking (see McDonald, 2002). Thus, parents of DMD patients are left with fundamental questions like, “Does exercise help or hurt my child?” and “What are the specific guidelines for ensuring that the exercise is safe and beneficial, and importantly, not detrimental?”

Where are we currently? In our 2007 ESSR review on this topic, we reported that exercise in various forms has been used to treat muscular dystrophy for more than 50 years. However, the sum total of the evidence lacked the necessary rigor to define exercise intensity, duration and frequency. We proposed that studies be first conducted in dystrophic mice, then dystrophic dogs, and ultimately that a clinical trial be initiated. In 2008, a roundtable to discuss the scientific lines of inquiry for exercise as a treatment for DMD convened at the New Directions in the Biology and Disease of Skeletal Muscle Meeting in New Orleans. Basic scientists, physicians and physical therapists contributed to the discussion. We agreed that the overarching purpose of exercise studies should be to identify the parameters of potentially beneficial versus potentially detrimental types and levels of physical activity and exercise for individuals with DMD. Two key recommendations that emerged were as follows:

• First, granting agencies should target funding and request proposals to determine the role of therapeutic exercise in the treatment of DMD.
• Second, a cornerstone for these studies should be translational research teams, including physical therapists, physicians and basic scientists.

Most recently, after further analysis of the available evidence, our group (Markert and colleagues) has suggested that appropriate exercise may counter some of the molecular mechanisms associated with DMD, such as inappropriate calcium influx, aberrant cell signaling and increased oxidative stress. Well-designed studies will help answer this possibility.

To make an informed decision about the role of exercise in DMD, rigorous scientific inquiry is still required. It is my hope that future studies will demonstrate definitively the evidence base to support (or not) properly prescribed exercise to treat DMD.

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