160 YOUNGSTERS ARE AMONG FINALISTS FOR MDA GENE THERAPY SAFETY TRIAL: MORE CANDIDATES SOUGHT

TUCSON, Ariz., Aug. 13, 1998 -- The Muscular Dystrophy Association today announced that 160 children from around the world are being evaluated for possible participation in a collaborative clinical trial to test the safety of gene therapy as a potential treatment for Duchenne muscular dystrophy. The boys currently being considered represent 41 states and 11 countries, including Australia, France, Germany, India, Korea, South Africa, Spain and Turkey.

Following a two-day gene therapy workshop (Aug. 2-3) in Tucson focused on accelerating development of protocols for muscular dystrophy clinical trials, MDA made known its interest in registering for additional gene therapy trials youngsters with Duchenne or Becker muscular dystrophy, as well as adults with Becker and limb-girdle muscular dystrophy.

The gene therapy workshop was chaired by Dr. James M. Wilson, director of the Institute for Human Gene Therapy at the University of Pennsylvania, and featured presentations by seven gene therapy pioneers, including Dr. Jerry Mendell of the Ohio State University Medical Center and Jeffrey Chamberlain of the University of Michigan. Mendell and Chamberlain are leading the clinical trial team that's narrowed the field of trial prospects from some 250 applicants to 160 finalists.

Other workshop participants were top clinicians and researchers from the Children's Hospital in Boston, Emory University (Atlanta), the Ohio State University Medical Center (Columbus), University of Iowa College of Medicine (Iowa City), University of Miami, University of Pennsylvania Health System (Philadelphia), Washington University School of Medicine (St. Louis), University of Washington (Seattle), and the University of Oxford in London.

The Association also reported that air travelers who use United Airlines, which is an MDA national sponsor, have contributed millions of frequent flier miles to help transport trial participants to Ohio State University Medical Center, where gene therapy injections ultimately will be made.

"We stand at the threshold of the most important clinical trials in MDA's history. The finest medical and scientific minds in the world are sharing their data and their expertise to accomplish what we hope will yield a safe and effective treatment for muscular dystrophy," said Donald S. Wood, MDA director of science technology. "Yet," Wood added, "if several hundred more patients do not register as potential clinical trial participants, progress may be slowed."

"The incredibly informative and sometimes heated discussions we had during this two-day workshop should quickly yield a most appropriate clinical trial protocol to advance to the Food and Drug Administration for consideration as an Investigational New Drug, or IND, for Duchenne muscular dystrophy," said Mendell, director of the MDA clinic at Ohio State University Medical Center.

"MDA researchers have accomplished so much that we're all eager to get underway with clinical trials," he added. "But everyone agrees that first and foremost we must evaluate every possible safety nuance for this experimental therapy. The pledge from all concerned is to maximize what we can learn from safety studies to minimize the risk to children with Duchenne muscular dystrophy eventually selected for future trials."

Mendell and Chamberlain plan to use a gene delivery system that's worked well in the laboratory and is capable of carrying the incredibly large gene that produces the dystrophin protein. Dystrophin plays a critical role in maintaining the structure of muscle cell membranes. Absence of the protein leads to increased cell injury, and eventual destruction of the muscle. Boys affected by Duchenne muscular dystrophy usually lose the ability to walk in late childhood, and die from respiratory insufficiency in their 20s. Those with Becker muscular dystrophy are less severely affected.

Mendell is experienced with clinical trials for muscular dystrophy. He led a three-year clinical trial (1992-1995) in which healthy immature muscle cells, or myoblasts, were injected into the muscles of youngsters with Duchenne muscular dystrophy.

Chamberlain led a team of researchers that in 1996 created one of the first gene delivery systems to improve prospects for reducing or eliminating host immune response. His team removed all viral genes from the adenovirus, opening up space for the therapeutic dystrophin gene, which is some 200 times larger than most other genes. Chamberlain also led a team that in 1993 proved gene therapy can halt Duchenne-like muscular dystrophy in mice.

"The focused feedback we received from peers during MDA's two-day gene therapy workshop will prove invaluable," Chamberlain said.

"Equally important, the candid discussion surrounding plans at the University of Pennsylvania to use other gene delivery systems in clinical trials for limb-girdle muscular dystrophy, and the impressive gains Wilson's team has made in the manufacture of gene delivery systems are most heartening," Chamberlain added.

The team at Penn plans to test a novel gene delivery vehicle, a very small virus based on a defective human virus in the treatment of limb-girdle muscular dystrophy. Experiments in animal models have been encouraging.

"Tremendous progress has been made in the development of vehicles to transfer healthy genes to muscle," Wilson said. "The clinical trials we are preparing for should pave the way for progress against a wide array of diseases."

Since the discovery of the dystrophin gene in 1986, MDA-funded scientists have pioneered gene therapy research in their efforts to develop cures for the host of genetic neuromuscular diseases included in the Association's program.

Efforts have been hampered by three major obstacles: the size of the dystrophin gene prevents its administration by the common viral gene vectors; large numbers of cells must contain the gene in order to improve muscle strength; and animal experiments suggest immune rejection of cells infected by the vector may limit the duration of the gene correction.

MDA is a voluntary health agency working to defeat 40 neuromuscular diseases through programs of worldwide research, comprehensive patient and community services, and far-reaching professional and public health education.

Recognized by the American Medical Association with a Lifetime Achievement Award "for significant and lasting contributions to the health and welfare of humanity," MDA maintains more than 230 hospital-affiliated clinics that offer families the best in care for progressive neuromuscular diseases.

MDA annually funds some 400 scientific teams worldwide. These investigators have made significant advances toward cures for several muscle-wasting diseases. They've pioneered breakthroughs that may well lead to therapies for heart disease, cancer, AIDS, Alzheimer's, Parkinson's, Huntington's and cystic fibrosis. For information about these gene therapy projects, MDA and/or referrals to MDA clinics, call 1-800-572-1717, or visit MDA's Web site at www.mda.org. MDA programs are funded almost entirely by individual private contributors.