NIH awards three grants to explore novel treatment strategies for muscular dystrophy

Three grants totaling more than $4.5 million, from agencies of the National Institutes of Health, will be used to explore novel treatment strategies for muscular dystrophy.

The grants were awarded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Neurological Disorders and Stroke (NINDS) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for year one of five-year cooperative agreements.

The grants designate Nationwide Children's Hospital, Columbus, Ohio, as a Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (MDCRC), and continue funding of crucial research by two previously established MDCRCs at the University of Pennsylvania, Philadelphia and the University of Iowa, Iowa City.

Researchers at Nationwide Children's Hospital, under the direction of Jerry Mendell, M.D., will further develop methods to overcome immune barriers to gene correction for Duchenne muscular dystrophy (DMD). A form of muscular dystrophy that affects children and young adults, DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Gene therapy for DMD includes injecting genes for a functional version of the muscle protein dystrophin, encased in a virus designed to deliver the gene into the muscle cells. In an early trial of this experimental therapy, blood analyses and biopsy slides showed that the immune system in more than half of the children mounted a response to dystrophin or the viral delivery vehicle.

The goal of the research will be to see how many patients have pre-existing immunity to dystrophin that could block the gene transfer. Researchers also will determine if the immune reaction could be circumvented by removing antibodies with a blood-purifying procedure called plasmapheresis or administering drugs that suppress the immune response.

At the University of Pennsylvania, researchers led by H. Lee Sweeney, Ph.D., will research treatments to inhibit muscle fibrosis, or scarring, that causes muscle dysfunction. By reducing scar formation, such treatments may not only improve muscle function, but may also enhance muscle regeneration and increase the effectiveness of drug, gene and stem cell therapies for muscular dystrophies (MD). The research aims to identify existing drugs that inhibit fibrosis, as well as drive the development of new classes of fibrosis inhibitors. The center's goal is to develop non-invasive imaging techniques to assess the replacement of skeletal and cardiac muscle with fat and scar tissue associated with MD progression.

Research at the University of Iowa, directed by Kevin Campbell, Ph.D., will explore therapeutic strategies for the treatment of various muscular dystrophies arising from the abnormal processing of muscle proteins called dystroglycans. This will involve investigating what happens on a molecular level in these dystrophies (called dystroglycanopathies) and evaluating various treatment strategies, using mouse models and cells with known mutations from dystroglycanopathy patients. It will also entail identifying and characterizing dystroglycanopathy patients and developing infrastructure for trials of dystroglycanopathy treatment in defined patient groups.

Muscular dystrophy is a group of debilitating, and often fatal, diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles, which control movement and breathing. MD can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later.

Source: NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases