Physicians at Duke University Medical Center are leading a national study to learn whether stem cell transplants can correct defective immune systems in patients with scleroderma, a disabling and sometimes deadly disease.

If they work, such transplants would be the first therapy to treat -- and possibly even reverse -- scleroderma. Current treatments just ease its symptoms.

Success also could lead to effective treatment for other autoimmune diseases, which affect more than 20 million Americans.

Scleroderma, like all autoimmune diseases, develops when a person's immune system malfunctions in response to an unknown trigger and attacks body tissue.

"We've used scleroderma because it's the toughest case," said Dr. Keith Sullivan, a Duke oncologist who is lead investigator in the clinical trial. Duke is one of seven transplant centers nationwide participating in the trial and the only one in the Southeast.

With scleroderma, the immune system targets connective tissues throughout the skin and internal organs, causing a cascade of symptoms that can include pain, inflammation, hardened skin and failure of the lungs, kidneys and other organs. Scleroderma is often minor, and it is not contagious.

But about 100,000 people in the United States suffer systemic disease that rapidly spreads throughout their bodies. About half of them die within five years of diagnosis, Sullivan said.

The cause of the disease is not known, though physicians think a combination of genetics and exposure to certain chemicals or environmental contaminants is probably responsible. Doctors also suspect the female hormone estrogen plays a role in triggering it, which could explain why scleroderma occurs three to four times more often in women.

Other autoimmune diseases include lupus, Type 1 diabetes, rheumatoid arthritis and multiple sclerosis. As many as 23.5 million Americans have an autoimmune disorder, according to the National Institutes of Health.

The seven-year scleroderma study, supported by a $20.5 million grant from the NIH, will compare two possible treatments in 226 patients.

Half the participants will get total body radiation and chemotherapy to kill their flawed immune systems. Then they will receive a transplant of stem cells collected from their own blood. The hope is that the stem cells, which have the unique ability to become different types of cells or tissue, will generate a new immune system that does not attack the connective tissue.

The other half of trial participants will get monthly infusions of cyclophosphamide, a cancer drug that is often used to treat scleroderma symptoms. Patients will get higher doses and for a longer duration than commonly prescribed. The goal is to suppress the immune system so that it behaves less aggressively and symptoms slow or stop.

Stephen Williams, 46, who had a stem cell transplant at Duke in May, is optimistic the treatment may allow him to continue as a social worker. Except for the time he took for the transplant, the Louisville, Ky., resident has not missed work because of his scleroderma. But the disease is affecting his lungs, causing him to wonder when he might be disabled.

"My disease seemed to come on pretty quickly," he said. "The hope is that [the stem cell transplant] can improve or reverse it."

Sullivan stumbled onto the idea of treating autoimmune disease with stem cell transplants while practicing at the Fred Hutchinson Cancer Research Center in Seattle in the mid-1990s. Blood cancer patients who got transplants, and who also suffered from autoimmune disease, reported that their autoimmune symptoms eased or appeared to go away.

Sullivan then led a preliminary study that showed 19 of 33 scleroderma patients treated with such transplants saw no further progression of their disease.

Vulnerability is risky

Stem cell transplant as a therapy for autoimmune disease is not limited to scleroderma. Duke is participating in an NIH-funded clinical trial of 100 patients to test such transplants for lupus. NIH also is funding a preliminary study that will look at the transplants to treat multiple sclerosis.

Still, some doctors who treat autoimmune diseases are skeptical.

Wiping out patients' immune systems is dangerous because it makes them vulnerable to infections. A nasty bug can be deadly if it gets ahold of them before their immune systems regenerate. Five of the 33 scleroderma patients in Sullivan's preliminary study died of therapy-related causes. Just as many patients died from the effects of the disease.

"As a treating physician, how do you convey the risks?" said Dr. Nortin Hadler, a professor of medicine at UNC-Chapel Hill and attending rheumatologist at UNC Hospitals. He has an active caseload of about 100 scleroderma patients, some of whom come to him from outside North Carolina.

Still, he said, he is eager to see the trial's results.

"In the best of all worlds, [stem cell transplants] will work for the rapidly progressive group, and we'll see less and less of the end-stage disease," Hadler said.

In spite of his earlier work, Sullivan reserves judgment about which treatment being tested will be better. "There are compelling data for both camps," he said.

Williams, the patient from Louisville, thinks transplants will be more effective.

He was diagnosed with systemic scleroderma in May 2005, six months after his hands began to become red and swollen. By the time he came to Duke in August to discuss participating in the scleroderma trial, the disease had attacked his lungs, and his hands were so stiff he found it difficult to make a fist. He took Tylenol two or three times a day for joint pain.

Since his transplant, Williams hasn't needed pain medicine, and the tightness in his hands is getting better. He headed home to Louisville last week, where he will be monitored by a doctor there who is participating in the trial.

"I'm real hopeful," Williams said. "I feel like it's working."