The NICHD is one of many federal agencies and NIH institutes working to understand muscular dystrophy (MD).
Institute Activities and Advances
The NICHD's Intellectual and Developmental Disabilities Branch (IDDB) sponsors training in muscle biology and MD research aimed at preventing and ameliorating intellectual and related developmental disabilities.
Past and present IDDB-supported research on MD includes drug therapy to help alleviate the symptoms of myotonic MD as well as several studies focused on Duchenne MD (DMD). These include the following:
- Studying the effects of glucocorticoid treatment—the current standard of care for DMD—on the immune system to help researchers better understand why the immune system blocks gene correction methods.
- Developing a two-tiered newborn screening: examining creatine kinase (CK) levels in the blood and then testing for gene mutations in infants with CK levels already determined to be elevated. This helps to correct for false positives and to predict DMD gene mutations. For more information on this finding, visit http://www.ncbi.nlm.nih.gov/pubmed/22451200.
- Successful application of exon-skipping on canines. Genetic researchers treated dogs with canine X-linked MD, which is similar to DMD in humans. "Exon-skipping" uses synthetic DNA-like molecules called antisense to skip over the parts of the gene that block the creation of dystrophin. Because the gene'smutation could affect any of its 79 exons and sometimes more than one exon at a time, scientists created a "cocktail" of antisense called morpholinos to ensure that all of the mutations are covered. This treatment has the potential to benefit 80% and 90% of DMD patients. For details on this finding, please visit http://www.childrensnational.org/pressroom/NewsReleases/FirstExonSkippingLargeAnimal.aspx.
In addition, the NICHD's National Medical Center for Rehabilitation Research (NCMRR) leads two programs that support research for people with MD.
- The Spinal Cord and Musculoskeletal Disorders and Assistive Devices (SMAD) Program focuses on developing and supporting the application of devices to improve patients' interactions with their environment and to restore or enhance their capacity to function in that environment. The program supports the development of rehabilitation technology such as prosthetics and wheelchairs as well as applied research in biomechanical modeling and other topics that aim to enhance mobility, communication, cognition, and environmental control. Researchers recently studied the signaling response from transforming growth factor b (TGFb), a protein that plays a role in the development of many conditions, including heart disease and MD. They discovered that decreasing signaling from TGFb lessens skeletal and heart muscle malfunction.
- The Behavioral Sciences and Rehabilitation Technologies (BSRT) Program leads the NCMRR's efforts to support research for developing assistive technology aimed at helping individuals with disabilities perform daily activities. The behavioral science aspect of this program conceptualizes, initiates, and supports scientific efforts designed to advance knowledge relevant to the role of the behavior of individuals with physical disabilities. The rehabilitative engineering portion of the program develops and supports the application of engineering and bioengineering principles to study the habilitation of individuals with disabilities.
Recent NCMRR advances in MD research include the following:
- In Long-term Animal Model of DMD, Losartan Reduced Mortality and Improved Heart Function: Losartan, a drug used to treat high blood pressure, has shown positive results on muscle function and strength in short-term animal models of DMD. The next logical step was to conduct longer-term studies in animals. In addition, previous animal studies have not determined losartan's impact on cardiac function. Identifying cardiovascular problems is especially important because heart failure is a common cause of death in young men with DMD. Scientists examined the effects of long-term losartan treatment in mice with DMD. Researchers found that after long-term treatment with losartan, 88% of treated mice were alive, compared with only 44% of untreated mice. While cardiac muscle function was significantly preserved in the treated mice, there appeared to be no change in the weight, morphology, and function of skeletal tissue. These findings suggest that losartan could be an important prophylactic treatment for heart disease associated with DMD but that the drug may not have a positive impact in the long run on DMD-associated skeletal muscle disease. For details on this finding, visit http://www.ncbi.nlm.nih.gov/pubmed?term=21731628.
- Study Offers New Insights for MD Therapy: MD is caused by mutations in genes that encode a complex of proteins associated with dystrophin (a protein involved in maintaining the integrity of muscle). People with MD also develop diseases of the heart muscle that enlarge the heart and make it more rigid than normal. Researchers have observed that signaling from TGFb is often increased in humans and in animals with MD. However, it was unclear whether this type of TGFb signaling actually causes abnormalities in the muscle. Understanding the processes that contribute to muscle damage may point the way toward new treatment approaches. Using a genetically altered fruit fly that develops progressive muscle and heart dysfunction similar to human MD, the researchers studied whether TGFb signaling drives the progression of MD. They found that TGFb signaling occurred immediately adjacent to the sites of exercise-induced muscle injury. By genetically decreasing the signaling, researchers were able to lessen skeletal and heart muscle malfunction. The study suggests that scientists should explore trying to develop treatments that target the TGFb pathway. To learn more about this research, visit http://www.ncbi.nlm.nih.gov/pubmed/21138941.
Other Activities and Advances
The NICHD is also active in the following projects that are related to MD research:
- The goal of the Wellstone Muscular Dystrophy Cooperative Research Centers (MDCRCs), supported through the IDDB, is to foster the translation of new scientific findings and technological developments into novel treatments for MD. The NICHD funds two of the MDCRCs, one at Research Institute of Nationwide Children's Hospital and one at Boston Biomedical Research Institute. The IDDB also funds opportunities for career development programs among junior investigators affiliated with the NICHD-funded MDCRCs. Three current career development programs provide support for MD investigators in laboratory research and patient-oriented research with the goal of increasing the number of researchers and the quality of research and training.
- The IDDB-funded NICHD Brain and Tissue Bank for Developmental Disorders aims to advance the research of developmental disorders, including MD. The objective of this human tissue repository is to systematically collect, store, and distribute brain and other tissues for research dedicated to the improved understanding, care, and treatment of individuals with developmental disorders. The bank has a separate website for tissue donors and their families, as well as a donor registry.