NONVIRAL, INTRAVASCULAR APPROACH
TO MUSCULAR DYSTROPHY GENE THERAPY MOVES AHEAD

TUCSON, Ariz., June 3, 2004 — Delivering genes for a key muscle protein via an intravascular route appears safe and effective in mice, the Muscular Dystrophy Association announced today at a meeting of the American Society of Gene Therapy in Minneapolis.

Dystrophin is a protein that stabilizes the muscle cell membrane. It’s missing in Duchenne muscular dystrophy, a severe, childhood-onset form of MD, and deficient in Becker MD, a somewhat less severe form of the disease that can begin in childhood or later.

MDA grantee Jon Wolff in the Department of Pediatrics at the Waisman Center, University of Wisconsin-Madison, announced the results of studies he conducted in combination with a private biotechnology company, Mirus, also located in Madison. Wolff is a co-founder and chief scientific officer of Mirus.

The researchers injected full-length, human dystrophin genes that weren’t encased in viruses into a leg vein in four dystrophin-deficient mice, after applying a tourniquet around the upper leg of each animal to keep the injected DNA concentrated in one area and targeted to that region’s muscles.

The injections were made into a vein in the direction of normal blood flow.

Encasing genes in viruses for transport into muscles or other tissues has been a popular approach in gene therapy experiments for the last decade and is still an important strategy. However, Wolff’s “naked” DNA strategy may be more advantageous in that it doesn’t seem to provoke an unwanted immune response, which sometimes occurs when viral coatings are injected into the body.

The researchers found that 3 percent to 15 percent of the leg muscle fibers in the mice showed dystrophin production, while the expected percentage of dystrophin-producing fibers in these animals would be below 0.5 percent.

“The demonstration that genes can be delivered safely and effectively to many limb muscles at once is an absolutely critical step in moving gene therapy from the theoretical realm to that of a realistic treatment for muscle disease,” said Sharon Hesterlee, MDA’s director of Research Development.

In addition to the mouse experiments using the dystrophin gene, the team scaled up gene delivery, using different genes, in larger mammals and obtained similar promising results.
“This advance will revolutionize the treatment of many heretofore untreatable disorders,” Wolff said. “This is something we have been working toward for almost 15 years, and we’re very excited about the hope this offers for people with muscular dystrophies. I never thought the solution could turn out to be this simple.”

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