| Overview of the Center The MD-CARE Act signed into law in December 2001 called for the creation of centers of excellence across the country to accelerate muscular dystrophy research. Six centers named after the late Senator Paul D. Wellstone, are supported by a collaboration among the NIAMS, NICHD and NINDS of the National Institutes of Health. A Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center was awarded to a joint Johns Hopkins and University of Pennsylvania group of researchers. Dr. Lee Sweeney from the University of Pennsylvania and Dr. Kathryn Wagner from Johns Hopkins direct the center. Principal investigators of the center are Drs. Se-Jin Lee and Kathryn Wagner of Johns Hopkins, Drs. Lee Sweeney and Elisabeth Barton of the University of Pennsylvania and Dr. Kenneth Fischbeck of NINDS. The goal of our Wellstone Center is to study mechanisms to modulate muscle growth and breakdown for treatment of a variety of muscular dystrophies.The muscular dystrophies are characterized by progressive loss of strength over time. Stimulating muscle growth may delay the time before significant disability and death. IGF-I is a potent stimulator and myostatin a specific inhibitor of muscle growth. Modulation of both pathways has been shown to ameliorate the mdx model of muscular dystrophy. Recently, protease inhibition with Bowman Birk Inhibitor Concentrate (BBIC) has been found to have similar effects. The center is composed of three sites, the Johns Hopkins School of Medicine, the University of Pennsylvania and intramural NINDS and includes investigators who are leaders in the field of myostatin and IGF-I as well as clinical experts in muscular dystrophy. In Project 1, Dr. Se-Jin Lee is elucidating mechanisms by which myostatin activity is regulated with the goal of developing therapeutic agents targeting myostatin activity. In Project 2, Dr. Lee Sweeney is studying the effects of inhibiting protein breakdown while stimulating muscle growth in mouse and canine models. In Project 3, Dr. Kathryn Wagner is exploring the potential synergistic actions of modulating both IGF-I and myostatin pathways. In Project 4, Dr. Kenneth Fischbeck will direct a clinical trial with the protease inhibitor, BBIC in Duchenne muscular dystrophy. There are two core facilities: Administrative and Training Core A provides administrative and scientific support for the entire center as well as facilitates training of new investigators in the area of muscular dystrophy. Physiology Assessment Core B provides a resource to the Center and others in the muscular dystrophy community to test various functional parameters of muscle in animal models. Modulating muscle growth is an immediately applicable approach to a variety of muscular dystrophies with IGF-I, a myostatin inhibitor, and protease inhibitors already in clinical trials. This MDCRC will provide needed basic, translational and clinical data on the safety and effectiveness of this approach. |