MEDICINE GENETICS : Muscular Dystrophy Advance Reported

For the second time in three weeks, researchers have reported promising results in humans with a proposed new genetic therapy for Duchenne muscular dystrophy.

At a Wednesday press conference, a Canadian researcher said that the unusual therapy has been found to be both safe and feasible in tests on three young boys, but that it is too early to tell if the treatment is effective in reversing the course of the disease.

The new therapy involves injecting healthy muscle cells alongside diseased muscles. Experiments in animals suggest that the injected cells will fuse with the patient’s muscle cells and cause them to produce a protein that is missing in victims of the degenerative disease.

Three weeks ago, neurologist Peter J. Law of the University of Tennessee reported that the therapy led to the production of the missing protein in a small toe muscle of a 12-year-boy with the disease--the first time that any form of genetic therapy has been shown to work in humans.

The new findings announced by neurologist George Karpati of the Montreal Neurological Institute represent a significant step beyond Law’s results, experts said, because the muscle he studied--the biceps of the arm--is 30 times as large as the toe muscle and requires the injection of a much larger number of cells, as many as 60 million.

Wednesday’s confirmation of the earlier results “gives us cause to be optimistic” about the success of the therapy, said pediatric neurologist Leon I. Charash, chairman of the Muscular Dystrophy Assn.’s medical advisory committee, “but it is still very early in the game.”

But Karpati refused to reveal whether the treated muscles were producing the missing protein. “We don’t want to make any premature statements about efficacy of the therapy because we don’t want to raise false hopes,” he said. But Karpati is optimistic that the treatment will be found to be effective, and he is laying the groundwork for studies in which the healthy cells will be fused with more vital muscles, such as those that control breathing.

Meanwhile, researchers in San Francisco plan to begin human trials of the new therapy in August or September, and a separate group in Boston will begin by the end of the year. Karpati said he hopes that his report of the safety of the procedure will stimulate other researchers to try it, thereby increasing the likelihood that an effective treatment regimen will be discovered.

About one in every 3,500 boys born in the United States has the genetic defect that causes Duchenne muscular dystrophy. Females can be carriers of the gene, but rarely contract the disorder.

The affected babies appear normal at birth, but develop a progressive weakening of the muscles that usually places them in a wheelchair by the age of 11. There is no current therapy and most die in their late teens or early 20s when the muscles that operate the heart and lungs cease functioning.

The new results are all the more surprising because it was only 2 1/2 years ago that researchers discovered the defective gene that causes Duchenne MD. The healthy gene is the blueprint for a protein, called dystrophin, that allows muscle cells to function properly.

The new therapy is possible because each muscle cell, unlike cells elsewhere in the body, has hundreds to thousands of nuclei, each with its own genetic information. Muscle tissue also contains immature cells, called myoblasts, that can fuse with existing muscle cells, insert their own healthy nuclei and cause the muscles to regenerate.

Karpati has so far treated three boys 6 to 8. In each case, he isolated about 10,000 healthy myoblasts from the boy’s father and grew them in the laboratory until he had obtained more than 60 million.

He then made a series of 55 injections along the biceps in one arm of each boy, injecting about 1 million cells at each site. An equal number of sham injections of salt water were made along the biceps of the opposite arm as a control.

Karpati noted that critics of the procedure argued that there were many possible deleterious effects that could be caused by the procedure, including rejection, infection, hemorrhage, scarring, prolonged pain and so forth. “None of these things happened,” he said.