A medical research team at Carolinas Medical Center (CMC), headed by Qi Long Lu, M.D., Ph.D. (pictured), has made a discovery that holds promise to restore muscle function in patients with Duchenne muscular dystrophy (DMD).
Dr. Lu and his colleagues have been utilizing a medical approach called “gene manipulation therapy” that – if ultimately proven safe and effective for humans – would offer new hope to DMD patients.
DMD patients suffer an affliction in which gene mutations prevent the body from producing a normal supply of dystrophin, 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 uses an approach called “exon skipping.” Exon skipping is intended to help the DMD patient's body again produce dystrophin that is at least somewhat functional, so that muscle cells will not break down and die over time, the way they do currently in patients afflicted with DMD. In recent years, the life expectancy of DMD patients has increased from roughly 20 years of age to roughly 30 years of age, due to better medical management and care. Currently, however, the effects of the disease cannot be stabilized or reversed.
Muscular dystrophy research efforts have been high profile in the United States, largely due to fundraising efforts by the Muscular Dystrophy Association (MDA), including the Jerry Lewis Labor Day Telethon and other awareness initiatives. MDA currently spends some 40 million dollars annually on biomedical research.
Dr. Herbert Bonkovsky, Vice President of Research at CMC, said that Dr. Lu’s work, in collaboration with scientists at other research centers, has great potential for benefit if experimental results in mice can ultimately be safely adapted for humans.
Dr. Lu, who came to work at CMC’s McColl-Lockwood Laboratory for Muscular Dystrophy Research in September 2004, said that his team is looking forward to the next step in DMD research. His current article explains in detail 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. “Our eventual goal,” he said, “would be a treatment regimen for human patients that would rely on intravenous injections every couple of weeks.”
Dr. Bonkovsky said the therapeutic 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 he and his colleagues have been 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 he was pleased to see Dr. Lu’s work publicized in such a well respected academic journal. “It is significant when research findings hold up to such a rigorous process of peer review,” he said. “DMD is a dreaded disease that impacts an estimated 10,000 patients in our country. It is heartening to see new developments that offer hope to patients who have one of the most common and severe forms of MD.”
Illustration: Carolinas Medical Center.
Carolinas Medical Center News Release (09/16/08)
The Earth Times (09/18/08)
News-Medical Net (09/21/08)
Abstract (Proceedings of the National Academy of Sciences of the United States of America; Vol. 105, No. 39, 14814-14819 (09/30/08))