As a swimmer, Dongsheng Duan understands the importance of muscle strength. As a surgeon, he has seen patients suffer from muscle deterioration. As a researcher, Duan is seeking a cure for a particularly painful type of muscular dystrophy that strikes young boys.
Duchenne muscular dystrophy usually appears around age 3 and attacks the muscles in about one of every 3,000 boys. Its progression is more predictable than other forms of muscular dystrophy, at first affecting the voluntary and skeletal muscles in the arms, legs and trunk. By adolescence, heart and respiratory muscles begin to deteriorate. If the cardiac muscle is not strong enough to supply blood to the rest of the body, the patient’s life will be threatened. Not many patients survive past their 30th birthday.
About 30 percent of DMD patients die of cardiac problems. Most of the research for a cure has focused on the skeletal muscles. Existing treatments are aimed at strengthening bones and improving mobility of patients with catabolic steroids and calcium supplements. However, they don’t stop the muscles from deteriorating.
In his lab at University Hospital, Duan has been experimenting with gene therapy to protect and strengthen a single muscle — the heart. The goal is to make the heart strong enough to withstand DMD’s attack on the rest of the body.
Researchers have identified the cause of DMD as a mutation of the gene that generates a protein called dystrophin. The gene actually fails to make dystrophin, which results in the degeneration of muscle tissue. For several years now, with funding from the Muscular Dystrophy Association and the National Institute of Health, Duan has been looking for a way to introduce the dystrophin gene directly into the heart.
Because the gene is too large and difficult to work with, Duan’s collaborator, Jeff Chamberlain of the University of Washington, developed a smaller version, called micro-dystrophin.
Duan’s achievment is the development of a recombinant adeno-associated virus that would actually deliver the micro-dystrophin to the heart muscle. Duan’s virus does not carry disease, but its size makes it the perfect vehicle for delivering the micro-dystrophin. The new gene should take over and correct the defect of the old gene. Studies by Duan and his collaborators have shown that, in mice, the new genes have strenghtened the cardiac muscle.
An assistant professor at MU, Duan performs his research when he isn’t teaching virology to a class of mostly graduate students. He loves teaching and tries to instill a work ethic and natural curiosity in future scientists.
“Students can become more independent with your influence,” Duan said.
Duan, 39, earned his medical degree in China. He became a surgeon in his native country, but eventually became bored because as a young doctor, he wasn’t allowed to work on any exciting cases. He moved to the U.S. in 1993 and earned his Ph.D. from the University of Pennsylvania in 1997. Before coming to MU in February 2002, Duan did research into cystic fibrosis at the University of Iowa.
After coming to the lab around 8 a.m., Duan usually spends his days preparing and conducting experiments, responding to emails, writing grants and articles and checking on his students. With all this, he shyly admitted that he still tries to find a half-hour at lunch to swim some laps.
Duan has an 11-year-old son named Sean with his wife, Yongping Yue, also his senior research assistant. Duan said he persuaded her to work with him because he knew good lab technicians were hard to find and even harder to keep. He credits her for doing most of the work on Duan’s published articles, the most recent of which appeared in the September issue of Circulation, the top medical journal on cardiovascular research.
Duan’s immediate goal with his research is to improve the level of expression in each gene cell and to introduce more cells into the heart with an improved technique. He hopes his scientific breakthrough will someday be able to help human patients.
“Even if you’re not a doctor, I guarantee everybody in their life has been a patient,” Duan said. “So if there’s anything we can do, even though it’s pretty small, I feel like it’s a great reward.”