FRENCH GENE TRANSFER STUDY IN DMD, BMD
LOOKS SAFE, PROMISING

The AFM -- Association Francaise Contre les Myopathies, or French Association Against Muscle Diseases -- in conjunction with Transgene, a biotechnology company based in Strasbourg, today announced that a nonviral approach to gene therapy in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) appears safe and holds promise for future effectiveness against these diseases.

MDA grantee Jon Wolff of the Department of Pediatrics at the University of Wisconsin at Madison was part of the French project.

The announcement was made at a meeting of the American Society of Gene Therapy in Washington.

Wolff developed much of the strategy used to deliver the therapeutic gene, which carries instructions for the crucial muscle protein dystrophin. The protein is missing or flawed in people with DMD or BMD.

The dystrophin gene was first identified by MDA-supported researchers in 1986.

In the trial, results of which were announced today, investigators used a “naked DNA” delivery strategy that splices the desired gene into a piece of genetic material called a plasmid. They injected the plasmid-dystrophin combination directly into an arm muscle in 15 boys with DMD or BMD.

The study participants were divided into three groups, the first two of which received a single injection of 200 micrograms or 600 micrograms of the plasmid-dystrophin construct, while those in the third group received two injections of 600 micrograms, two weeks apart.

The investigators studied muscle samples 21 days after the first (or single) injections.

A small amount of dystrophin protein that was apparently made from the plasmid-dystrophin construct appeared in 1 percent to 10 percent of injected muscle fibers in half of the boys in the first two groups (three out of six in each group) and in all three boys in the third group. Dystrophin was present only in a small area around the injection site.

It’s generally believed that dystrophin production in about 20 percent of muscle fibers would make a significant difference in a muscle's function.

There were no signs of immune-system reaction against either the plasmid or the newly produced dystrophin, making the safety profile appear “excellent” to the researchers.

The AFM and Transgene are continuing to develop the nonviral DNA delivery system. Earlier experimental gene therapy strategies have delivered a corrected gene via a virus, which is more likely to trigger the immune system.

“These results demonstrate for the first time that it is possible to obtain local expression of dystrophin in patients with Duchenne/Becker muscular dystrophies following the administration of a plasmid containing the human dystrophin gene,” the AFM-Transgene group said in a statement released today.

Wolff, who has had MDA support since 1991, is now working on delivering genes under pressure through the body’s arteries so that several muscle regions can be targeted with few injections.