FIRST HUMAN TRIAL OF GENE THERAPY FOR MUSCULAR DYSTROPHY BEGINS
COLUMBUS, Ohio, Sept. 2, 1999 -- A 36-year-old air traffic controller from Huron, S.D., became the first person to receive a gene therapy injection for muscular dystrophy this evening. The first of an expected six participants in a Muscular Dystrophy Association-funded trial to determine the safety of this potential therapeutic, Donavon Decker has limb-girdle muscular dystrophy (LGMD). Dr. Jerry Mendell, chairman of the Department of Neurology at the Ohio State University Medical Center in Columbus, injected a muscle on the top of Decker's foot with genes for a muscle protein that's missing because of a genetic flaw.
The gene therapy trial was authorized by the Food and Drug Administration, and received a recommendation from the National Institutes of Health Recombinant DNA Advisory Committee earlier today. Led by investigators at Ohio State University and the University of Pennsylvania Health System in Philadelphia, the MDA trial is a collaborative effort involving investigators at the University of Iowa in Iowa City; the University of Rochester (NY); Washington University in St. Louis; Vanderbilt University in Nashville, Tenn; Emory University in Atlanta.
"I haven't been this excited since we found the first muscular dystrophy gene in 1986," said Jerry Lewis, MDA national chairman. "We're making final preparations for the Telethon this weekend, and we've now set the stage for what very well could be the payoff we've all been working so hard to achieve."
Gene therapy is the insertion of a working gene to compensate for genetic flaws, such as those that lead to muscular dystrophy, a progressive muscle-wasting disease that is debilitating and often fatal. LGMD, a form that affects tens of thousands of Americans, mostly damages the muscles that stabilize the hips and shoulders, is generally slowly progressive and often leads to wheelchair use by middle age. Serious complications can result if the heart and respiratory muscle become involved.
"I lost two brothers to muscular dystrophy," said Dr. Hansell H. Stedman, a University of Pennsylvania surgeon, who, in February, pioneered an innovative method to efficiently deliver therapeutic genes to skeletal muscle using the circulatory system. "So seeing gene therapy go from the rigors of the laboratory to the first human trial for muscular dystrophy is especially meaningful." Stedman was present for the historic injection, which took place at OSU Medical Center.
MDA grantee Kevin Campbell, a professor in the Department of Physiology and Biophysics at the University of Iowa, has identified several key proteins involved in different forms of muscular dystrophy. He determined the eligibility of patients scheduled to participate in this trial on the basis of molecular analysis of their muscle cells.
"I went from not knowing if there would ever be a cure to where we think now that it's just right around the corner," Decker said in an interview scheduled to air on the Jerry Lewis MDA Telethon this weekend (check local listings for time and channel). "It's kind of been a long waiting period, but this is the first step of the cure."
Decker received the genes for a sarcoglycan protein that belongs to a cluster present in healthy muscle-cell membranes. This protein cluster, which is repeated thousands of times around the perimeter of each muscle cell, is thought to protect the membrane during the stresses of contraction and relaxation.
The genes were injected using a highly modified virus developed by MDA researchers led by Dr. James M. Wilson, director of the Institute of Human Gene Therapy at the University of Pennsylvania. This "adeno-associated" virus isn't known to cause any human disease but has been altered to prevent its replication in the body to minimize risk for gene therapy trial participants.
One of Decker's foot muscles received the therapeutic genes, while the same muscle of the other foot received a sham injection. Researchers will take biopsies to compare the condition of the two muscles after six weeks.
They'll be checking to see whether the genes reached the cell nucleus, whether the needed sarcoglycan protein was produced from the genes, and whether that protein and other proteins normally associated with it ended up in the right place in the cells. They'll also be looking for any damage to the muscle cells.
Decker will be monitored closely for any adverse reactions, including immune response or other unwanted response to the virus used to carry the genes, to the genes themselves, or to the protein molecules produced by the genes.
"We're hopeful about the results of this pilot study," Mendell said. "But we want everyone to know it's only a first step. We don't expect Donavon or any other patient to directly benefit from this first trial, which is designed primarily to determine the safety of the procedure. However, we do expect that, if all goes well, we'll be injecting more patients soon, and that eventually we'll be looking at whether gene therapy can effectively stop the progression of muscular dystrophy."
In anticipation of this successful outcome, MDA is currently registering people with LGMD for further studies, which would include injections into a larger muscle to determine whether gene transfer actually improves strength. To register, call (800) 572-1717 or visit MDA's Web site, www.mda.org.
MDA is a voluntary health agency working to defeat 40 neuromuscular diseases through programs of worldwide research, comprehensive medical 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 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. MDA programs are funded almost entirely by individual private contributors, many of whom respond to the Jerry Lewis MDA Telethon. This work also was supported, in part, by the National Center for Research Resources and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
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