New type of gene manipulation therapy offers hope for Duchenne muscular dystrophy sufferers

Sep 21 2008

A medical research team at Carolinas Medical Center in Charlotte headed by Qi Long Lu, M.D., Ph.D., has made a discovery that holds promise to restore muscle function in patients afflicted by Duchenne muscular dystrophy (DMD).

Dr. Lu's findings are summarized in a peer-reviewed article that will appear in the September 30 edition of Proceedings of the National Academy of Sciences. Dr. Lu has been evaluating a new type of gene manipulation therapy that would -- if ultimately proven safe and effective for humans -- offer new hope to DMD patients.

DMD patients have gene mutations that prevent the body from producing a normal supply of dystrophin. Dystrophin is a protein that helps voluntary skeletal muscles (such as those that move the limbs and trunk) and heart muscle to function normally.

Dr. Lu's research relies on an approach called "exon skipping." Exon skipping helps an organism to produce dystrophin that is at least somewhat functional, so that muscle cells will not break down and die over time.

In recent years, the life expectancy of DMD patients has increased from roughly 20 years to roughly 30 due to better medical management and care. Currently, however, the effects of the disease cannot be stabilized or reversed.

Dr. Herbert Bonkovsky, Vice President of Research at CMC, said Dr. Lu's work has great potential for benefit if experimental results in mice can ultimately be safely adapted for humans.

Dr. Lu, who joined CMC's McColl-Lockwood Laboratory for Muscular Dystrophy Research in September 2004, said his team is looking forward to the next step in DMD research. His article details the laboratory trials that have produced measurable improvement in mice. "Toxicity has been tolerable," he said, "with no deaths, weight loss or adverse effects on the blood or on liver or kidney function."

If effectiveness holds up in subsequent research, scientists would eventually move to large-scale clinical trials in humans.

Dr. Bonkovsky said the concept being pursued by Dr. Lu is about 10 years old, but that therapeutic efficiency "has always been quite low until now." He said the exon skipping approach is only a few years old, and that CMC researchers are greatly encouraged by the recently observed successes in mice. These successes include the restoration of protein in all muscles, including the heart muscle, leading to improved muscle function.

Michael Rose, President of the Carolinas HealthCare Foundation, said Dr. Lu's research is funded by the Carolinas Muscular Dystrophy Research Endowment at Carolinas HealthCare Foundation, MDA (www.mda.org), and the U.S. Department of Defense.

"I am glad that the team at CMC has been given the support needed to assume an international leadership role. Dr. Lu was recruited to CMC from a prestigious position at the Royal College of Medicine in London, where he developed a global reputation in this highly specialized field. It speaks well for Carolinas Medical Center that we have him here."