The centers, also at the University of Washington, Seattle and the University of Rochester School of Medicine, New York, are each being funded for five years at up to $1 million a year. The Muscular Dystrophy Association is expected to issue an announcement of available supplements to provide up to $500,000 a year for three years at each center for additional projects.
A group of some 20 congenital muscle-wasting illnesses, muscular dystrophies are caused by genetic errors in a number of muscle genes. For example, the absence of a key muscle protein called dystrophin is the reason for Duchenne muscular dystrophy (DMD), the most common, debilitating and lethal childhood muscle disease, which affects about one in every 3,000 boys, according to the advocacy group Parent Project Muscular Dystrophy.
"We will develop strategies to treat these terrible diseases that threaten children's lives and make their lives miserable," said Joseph C. Glorioso III, Ph.D., chairman of the department of molecular genetics and biochemistry and director of the Molecular Medicine Institute at the University of Pittsburgh School of Medicine, principal investigator and director of the Pittsburgh center. "We also are working to find out more about the biology of these diseases."
Specific projects undertaken by scientists at the University of Pittsburgh involve preclinical and clinical studies of gene and stem cell therapies to treat muscle diseases – DMD in particular.
Gene therapy will be the focus of two Pittsburgh projects. Scientists led by Xiao Xiao, Ph.D., associate professor of molecular genetics and biochemistry, will be working in collaboration with University of Missouri and Ohio State University scientists on preclinical and clinical studies to determine the most effective ways to use adeno-associated viral vectors to deliver gene therapy. Dr. Xiao and others have redesigned the virus to deliver a payload of dystrophin protein. Previous studies have shown that the virus can establish the manufacture of dystrophin in injected tissues for at least a year. However, challenges remain to determine how best to use the virus to deliver gene therapy in a systemic way.
Clinical disease outcomes of these projects will be carefully defined in patients who have DMD and limb-girdle muscular dystrophies for the preparation of phase I gene therapy safety trials.
Another Pittsburgh project, led by Johnny Huard, Ph.D., associate professor of orthopaedic surgery, molecular genetics, biochemistry and bioengineering, will attempt to deliver and engraft muscle stem cells into diseased heart tissue without causing an immune response. Dr. Huard, who also is a deputy director of the McGowan Institute for Regenerative Medicine and director of the Growth and Development Laboratory at Children's Hospital of Pittsburgh, has extensive experience in using a unique population of muscle stem cells from healthy newborn mice to deliver dystrophin, a key protein for muscle function into animal models for DMD.
Additionally, researchers led by Dr. Glorioso will be using herpesvirus vectors in functional genomics studies to discover and characterize factors that guide stem cell maturation into muscle. Also working on the Pittsburgh team is Paul D. Robbins, Ph.D., professor of molecular genetics and biochemistry and co-director of the Pittsburgh center.
These new research centers in muscular dystrophies arise from the Muscular Dystrophy Community Assistance, Research and Education Amendments of 2001, or the MD-CARE Act, passed by Congress. They will encompass basic, clinical and behavioral research projects. Centers will work individually and collaboratively, and will be overseen by a steering committee, according to the NIH. Two additional centers are expected to be funded in future years.
Major forms of muscular dystrophy (MD) include myotonic, Duchenne, Becker, Emery-Dreifuss, congenital, limb-girdle and facioscapulohumeral. Duchenne is the most common form affecting children, and myotonic is the most common form affecting adults. 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.
Funding for the Pittsburgh projects is being provided through the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a component of NIH.
CONTACT:
Michele D. Baum
Lisa Rossi
PHONE: (412) 647-3555
FAX: (412) 624-3184
E-MAIL:
BaumMD@upmc.edu
RossiL@upmc.edu