MDA Researchers Combine Stem Cells, Gene Therapy in Duchenne MD

TUCSON, Ariz., Dec. 10, 2001 — Scientists funded by the Muscular Dystrophy Association announced today that, for the first time, they’ve used a combination of stem cell therapy and gene therapy to partially regenerate the muscles of mice with Duchenne muscular dystrophy.

The research offers hope for some 250,000 Americans affected by Duchenne and other forms of muscular dystrophy, a group of genetic diseases that cause muscle weakness and wasting. Duchenne — caused by a deficiency of the X chromosome gene dystrophin — almost exclusively affects boys, and typically causes death from respiratory failure in the 20s.

In a series of experiments, MDA grantee Johnny Huard and his colleagues at the University of Pittsburgh isolated stem cells from the muscles of mice with Duchenne, grew the cells in large numbers, fixed them with a corrective dystrophin gene and reintroduced them into the diseased mice. The stem cells fused with cells of dystrophin-deficient muscles in the mice, and made dystrophin-positive muscle fibers.

"If we could develop a similar type of therapy for people with muscular dystrophy — using their own stem cells to deliver corrective genes to their muscles — we could largely avoid problems with immune rejection," said Sharon Hesterlee, MDA’s director of Research Development.

In previous studies, mice and even people with Duchenne have been given muscle-derived cells from healthy donors. That procedure had limited success in mice and failed in humans, in part because the cells were targeted by the recipients’ immune defenses. Likewise, the best-studied gene therapy method — using a virus to deliver functioning genes to the body — can cause potentially dangerous immune reactions.

Huard’s studies are featured today in a press conference at the 41st annual American Society for Cell Biology meeting in Washington, and are being considered for publication in the Journal of Cell Biology.

One key to Huard’s experiments is that he’s isolated a population of stem cells that seem to have an improved capacity for repairing damaged muscle. Unlike cells that have been tested in the past, "when we inject these stem cells, they don’t just make muscle fibers. They make blood vessels, and they make peripheral nerve. They’re making muscle tissue," he said.

After isolating these cells from mice with Duchenne, Huard and his group infected the cells with a virus carrying minidystrophin — a miniaturized version of the dystrophin gene that was developed by MDA grantee Xiao Xiao at the University of Pittsburgh.

In one study, they gave intravenous injections of the stem cells to Duchenne mice that had their bone marrow destroyed. The cells restored the bone marrow, and some of them dispersed to muscles and other organs. In another study, the group transplanted the stem cells directly into muscle, where they fused with surrounding muscle fibers.

Unfortunately, in either case, the stem cells didn’t generate enough dystrophin-positive fibers to have a therapeutic effect in the mice. But Huard said he plans to improve the procedure, and begin searching for the same stem cells in people with Duchenne. He’s consulted with the Food and Drug Administration about setting up a clinical trial in youngsters with Duchenne, he said.

"This finding represents an important result of our research efforts in stem cells, gene therapy and other scientific avenues in which MDA has led the way for decades," MDA President Robert Ross said. "It’s a significant forward stride toward lifesaving cures or treatments for several forms of muscular dystrophy."

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education. The Association's programs are funded almost entirely by individual private contributors.