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Genetic roots of life-threatening disease target of MED faculty

By David J. Craig

For an incurable, life-threatening disease, scleroderma has a curiously low profile. About 150,000 Americans are afflicted with the painful, disfiguring autoimmune condition in which the body attacks itself with scar tissue, yet few people have even heard of it.

	Joseph H. Korn, a School of Medicine professor of medicine and biochemistry, is studying the genetic roots of scleroderma, a rare, potentially deadly autoimmune disorder that causes the hands, face, and internal organs to harden with scar tissue. Photo by Kalman Zabarsky

"There are as many instances of scleroderma in the United States as there are of muscular dystrophy, but that disease has a famous spokesperson, and scleroderma doesn't," says Joseph Korn, a School of Medicine professor of medicine and biochemistry, and the director of MED's Program in Scleroderma and Autoimmune Diseases. "There certainly are other rare diseases that are less devastating than scleroderma but better known."

Because scleroderma is relatively rare and unknown, few doctors specialize in its treatment, and research dollars to study it are modest. But since its formation six years ago, the Program in Scleroderma and Autoimmune Diseases, consisting of 10 MED faculty, has become one of the most prominent centers for scleroderma research and treatment in the nation.

"When you do bring together a group of people who have expertise in a disease like this, it's kind of like flypaper," says Korn. The program is part of the international Scleroderma Clinical Trials Consortium, which conducts multi-institutional trials on experimental therapies around the world. "At BU, I've treated patients from California, and we regularly get referrals from all over New England. That population base allows us to do large clinical trials."

Korn's own research focuses on identifying the genes involved in the production of collagen, a fibrous protein whose overproduction causes scleroderma, which typically strikes middle-aged women. Collagen is a major component of the connective tissues that bind the body together, such as the dermis -- the thick second layer of skin -- as well as tendons and scar tissue. In those with scleroderma, and for reasons that are still largely a mystery to scientists, collagen is released in extremely high quantities, causing the skin in the hands and face to become so leathery and tight that all mobility in those areas can be lost. In its worst form, scleroderma attacks internal organs, causing potentially fatal conditions such as interstitial lung disease, which involves the inflammation and scarring of lung tissue, and pulmonary hypertension.

"We're trying to identify what is abnormal in the chemical pathways that lead to collagen production in scleroderma patients, compared to normal individuals," says Korn. "That should give us some candidate genes for new therapies." The other main thrust of his group's basic research, Korn says, is studying naturally occurring compounds in the body that inhibit the production of collagen.

Faculty at the Program in Scleroderma and Autoimmune Diseases, meanwhile, are the lead investigators of a study funded by the Massachusetts Department of Public Health to determine if environmental factors contributed to the onset of scleroderma and lupus among several South Boston residents. In addition, the program is part of a national consortium that has applied to the National Institutes of Health to study a not-yet-approved method of treating scleroderma that involves bone marrow transplant.

"The bone marrow transplantation is a very experimental approach," Korn says. "Basically, it completely wipes out the immune system and then replaces it by transplanting into the bone marrow either the patient's or someone else's stem cells. Preliminary data show that the procedure itself is dangerous and that in one-third of the people who respond to the treatment, the disease comes back in 8 to 10 months.

"There are now effective treatments for some aspects of the disease, such as pulmonary hypertension, muscle inflammation, and lung inflammation," he continues. "Those treatments have contributed to an improvement in the disease's mortality rate over the years. Now, probably 80 percent of those with the disease survive for at least 10 years, whereas only 50 percent survived 7 years a couple of decades ago."

For more information about scleroderma and BU research on the disease, visit http://medicine.bu.edu/sc/sclero.htm.

29 March 2002
Boston University
Office of University Relations