Biennial Report of the Director

Centers of Excellence
Muscular Dystrophy Cooperative Research Centers

Establishment of the Wellstone Muscular Dystrophy Cooperative Research Centers

The Muscular Dystrophy Community Assistance, Research, and Education Amendments of 2001 (the MD-CARE Act, Pub, L. No. 107-84) included provisions for expanding and intensifying research on muscular dystrophy and mandated that NIH establish Centers of Excellence for muscular dystrophy research. Congress designated the centers as the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (Wellstone MDCRCs) in the Omnibus Appropriations for FY 2004 (Public Law 108-199) in honor of the former Minnesota senator who was a driving force behind the MD-CARE Act. The MD-CARE Act of 2008 officially renamed the centers.

How the Wellstone MDCRCs Function within the NIH Framework

NIAMS, NINDS, and NICHD fund the Wellstone MDCRCs through the U54 Specialized Centers Cooperative Agreement award mechanism (see Table 4-3). NHLBI also has co-sponsored the two most recent competitions for Wellstone MDCRCs, co-funds one Center, and plans to support projects within future Wellstone MDCRCs, if NIH receives fundable applications that address NHLBI’s mission.

A Steering Committee, consisting of directors and co-directors of each center and NIH science officers, coordinates the Wellstone MDCRCs’ scientific program. Through annual meetings, the Steering Committee promotes collaborations among center investigators, sharing of resources and exchange of scientific information.

Description of Disease or Condition

The muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive degeneration of skeletal muscles. Many dystrophies also affect other organ systems such as the heart, brain, blood vessels, and gastrointestinal tract (stomach and intestines). Some forms occur in infancy or childhood, whereas others usually do not appear until middle age or later. The Wellstone MDCRCs address, but are not limited to, the following conditions.

Currently, no treatment can stop or reverse the progression of any form of muscular dystrophy. Treatments such as physical therapy, use of appliances for support, corrective orthopedic surgery, and drugs can reduce symptoms and improve quality of life for some individuals. Some drugs, such as corticosteroids, can slow the progression of DMD to some extent, but have adverse effects. Several treatments, including gene therapy, cell-based treatments, and strategies to reduce muscle wasting have shown promise in experiments using cells and animals. Clinical trials of some therapies have begun, including the use of drugs to reduce muscle damage, approaches to increase muscle mass by stopping the activity of other proteins that inhibit muscle growth, and strategies to bypass mutations that cause disease.

Burden of Illness

DMD and BMD affect 1 in 3,500 to 1 in 5,000 boys, respectively. With more than 4 million annual births in the U.S., about 400 to 600 boys are born with DMD or BMD every year.2 Myotonic dystrophy affects approximately 1 in 8,000 people worldwide3, whereas FSHD affects approximately 1 in 20,000 people and affects men and women equally.4

The MD-CARE Act called for the CDC to collect and analyze information on the number, incidence, correlates, and symptoms of individuals with muscular dystrophy. Results from the project described the delay between the start of symptoms and definitive diagnosis of DMD.

2 For more information, see https://www.cdc.gov/ncbddd/musculardystrophy/data.html.
3 For more information, see https://ghr.nlm.nih.gov/condition/myotonic-dystrophy.
4 For more information, see www.nlm.nih.gov/medlineplus/ency/article/000707.htm.

Scope of NIH Activities: Research and Programmatic

As nationally recognized Centers of Excellence in muscular dystrophy, the Wellstone MDCRCs promote communication and collaboration, develop and share research resources, and help train new muscular dystrophy researchers. Each center can conduct a mixture of basic research to understand the diseases, translational research to turn basic research findings into interventions for patients, and clinical studies to test interventions in people. The overall focus of the Wellstone MDCRCs is to integrate activities to develop therapies for muscular dystrophies. An open competition led to one new Wellstone MDCRC in 2010, and the renewal of two that had received funds from the FY 2005 competition.

Collectively, the Wellstone MDCRCs conduct research on various forms of muscular dystrophy, including some not listed above. Examples of research topics addressed by the Wellstone MDCRCs in FY 2010 and FY 2011 follow.

Each Wellstone MDCRC has core facilities that provide unique resources or services for the muscular dystrophy research community. Cores include repositories of research data and biologic resources from patients with different types of muscular dystrophy, and assistance with gene therapy development and production. The Wellstone MDCRC program also supports facilities and personnel for testing candidate therapies in mice and dogs.

NIH Funding for FY 2010 and FY 2011

NIH funding for the Wellstone MDCRC program was $9.10 million in FY 2010 and $9.00 million in FY 2011.

FY 2010 and FY 2011 Progress Report

Programmatic Activities and Outcomes

Programmatic accomplishments in FY 2010 and FY 2011 include establishing a new Wellstone MDCRC at the Nationwide Children's Hospital, Columbus, Ohio, in FY 2010. In addition, the Wellstone MDCRCs at the University of Iowa and University of Pennsylvania competed successfully for renewal through FY 2015. The Children’s National Medical Center Wellstone MDCRC, funded under an earlier Wellstone competition, ended its formal center program in FY 2010. However, many of the center’s investigators continue to conduct muscular dystrophy research with support from other grants, including a Center for Research Translation award from NIAMS. Moreover, Children’s National Medical Center still is eligible to compete for a future Wellstone MDCRC grant.

The Wellstone MDCRC program has provided opportunities for public-private partnerships in muscular dystrophy. Projects have involved collaborations with, and additional support from, companies such as PTC Therapeutics and Insmed. The centers also have strong ties with patient advocacy groups and voluntary health organizations that promote and support muscular dystrophy research. These organizations are integral to the success of the Wellstone MDCRCs; they provide advice, assist with patient recruitment, and enhance the research through additional support. The synergy created by NIH resources and the involvement of industry and advocacy groups is accelerating progress toward muscular dystrophy treatments.

Because training and career development is an important component of the Wellstone MDCRC program, all current centers have formal training and education cores. These facilities provide stipends to predoctoral and postdoctoral researchers and enhance the programs’ educational environments.

Wellstone MDCRCs have leveraged other NIH funding in muscular dystrophy. In addition to awards reported in prior biennial reports, an NIH institutional training grant in neuromuscular disease has been awarded to investigators at Nationwide Children’s Hospital. Investigators participating in the University of Pennsylvania Wellstone MDCRC received an NIH program project grant for examining the mechanisms and potential therapeutics for muscular dystrophy-associated muscle fibrosis.

The Wellstone MDCRC core facilities are national resources for the muscular dystrophy research community. These facilities have been publicized at national meetings and through center Web sites and the Wellstone MDCRC Web site.5 These shared research tools foster collaborations across departments or schools within institutions, and among investigators and health care providers nationwide. Examples of these facilities include:

5 For more information, see https://www.wellstonemdcenters.nih.gov/index.htm.
6 Lemmers RJ, et al. Science. 2010;329(5999):1650–3. PMID: 20724583.
7 Phillips JL, et al. Methods Mol Biol. 2011;709:141–51. PMID: 21194026.

Research Activities and Outcomes

The Wellstone MDCRCs conduct basic, translational, and clinical studies related to a variety of muscular dystrophies. Examples of accomplishments in FY 2010 and FY 2011 are provided below.

8 Hilbert JE, et al. Contemp Clin Trials. 2012;33(2):302–11. PMID: 22155025.
9 For more information, see http://www.imagingdmd.org Exit Disclaimer.
10 Inamori K, et al. Science. 2012:335(6064):93–6. PMID: 22223806.

Recommendations for Improving the Effectiveness, Efficiency, and Outcomes of the Wellstone MDCRCs

Major review criteria for the Wellstone MDCRCs include the degree to which an institution shows that it can foster substantive collaborations among its researchers and with scientists elsewhere that address key issues in muscular dystrophy and its potential to serve as a national infrastructure and training resource. NIH responded to the burgeoning number of basic research findings in muscular dystrophy by changing the focus of the last two Wellstone MDCRC competitions (FY 2008 and FY 2010) to encourage research that translates basic findings about the disease to human studies and applications in the clinic. To further capitalize on NIH basic and translational research investments and accelerate progress toward effective treatments or other improvements in patients' lives, the next round of centers11 will be expected to involve clinical research with direct interactions between researchers and muscular dystrophy patients. In addition to therapy development, NIH will also encourage studies of the natural history of diseases, biomarker identification and validation, biopsychosocial studies, and other patient-oriented research. Centers may also contain basic and preclinical translational projects, as long as efforts are directed toward therapy development and other strategies for improving the lives of patients. NIH will continue to monitor the program’s coordination and productivity as staff review the progress of each center at the time of noncompeting renewal and through regular contact with Wellstone MDCRC leaders through the Steering Committee.

11 For more information, see https://grants.nih.gov/grants/guide/notice-files/NOT-AR-13-002.html.

Future Directions

NIH is committed to supporting six outstanding Wellstone MDCRCs. The agency issued three five-year awards to the Wellstone MDCRC program in FY 2010. In FY 2013, NIH plans to hold an open competition and intends to fund up to three Centers (for a total of up to six active Centers), pending the availability of funds.12 Grantees will join the network of Wellstone MDCRCs to translate scientific findings and technological developments into treatments for muscular dystrophies.

NIH supports multi-project grants and core centers for muscular dystrophy research at academic institutions, in addition to the Wellstone Centers. The agency also is promoting interactions among investigators at the Wellstone Centers and these other institutions to expand the scope and strength of the Wellstone Network.

12 For more information, see https://grants.nih.gov/grants/guide/notice-files/NOT-AR-13-002.html.

Table 4-3. Active Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (MDCRCs), FY 2010–2011
Institution and Location Years active
University of Rochester, Rochester, NY 2003–present
Children’s National Medical Center, Washington, DC 2005–2010
University of Iowa, Iowa City, IA 2005–present
University of Pennsylvania, Philadelphia, PA 2005–present
Boston Biomedical Research Institute, Boston, MA 2008–present
University of North Carolina, Chapel Hill, NC 2008–present
Nationwide Children's Hospital, Columbus, OH 2010–present