For the approximately 300,000 Americans suffering from scleroderma, a recent Duke study may provide hope for a viable treatment.

An autoimmune disease in which the body’s immune cells attack the skin—or even other organs, in some cases—scleroderma has been a notoriously difficult condition to treat. However, a paper published Jan. 4 in the New England Journal of Medicine showed that patients treated with a stem cell transplant showed more improvement in their condition 54 months later compared to patients treated with a chemotherapy drug.

“If you ask rheumatologists around the world ‘What’s the worst autoimmune disease?’ they will say scleroderma because it’s morbid, it’s mortal,” said Keith Sullivan, James B. Wyngaarden professor of medicine and lead author of the paper. “All the things that have been done over the last 40 years may have been modifying the symptoms and a benefit in the short term, but long-term mortality and survival has not changed, so that’s why this publication is newsworthy.”

The patients were split into a group of 36—which received the novel stem cell therapy—and a group of 39, which received a more traditional treatment with the chemotherapy drug cyclophosphamide, according to the paper.

Sullivan explained that this stem cell therapy had been previously tested in pilot studies and originated from researchers’ work with mouse models of autoimmune disease in the 1980s. These scientists found that subjecting the mice to radiation and a treatment involving their own stem cells could drastically improve their condition.

After smaller human trials yielded promising results, researchers organized this experiment with a larger cohort of participants. 

First, the researchers collected stem cells from the blood of patients suffering from scleroderma. Sullivan noted that they then eliminated the cells that were causing the disease—called autoreactive cells—before isolating the remainder of the healthy cells.

Patients in the experimental group received a whole-body irradiation treatment designed to “wipe the slate clean” by eliminating the scleroderma-causing, autoreactive cells still in the body, he added. Stem cells collected from the patients were then reinjected into the body to repopulate the blood stream with entirely healthy cells.

“[The therapy] works by reprogramming the immune system that has gone haywire,” Sullivan said.

Ankoor Shah, assistant professor of medicine and a rheumatologist who frequently sees scleroderma patients, praised the results and methodology of the study. The paper showed that stem cell therapy “can be a safe and effective treatment for patients with severe scleroderma,” Shah, who was not an author of the study, said.

Although the disease afflicts around 300,000 Americans, not all of them experience the same symptoms. Those with scleroderma that attacks both the skin and internal organs—totaling around 100,000 individuals—have a more “progressive, relentless mortality,” Sullivan added.

He noted that researchers have not definitively determined the cause of scleroderma but know that it results from some combination of genetic and environmental factors.

It has traditionally been difficult, Shah explained, for researchers to develop precise ways to measure a patient’s severity of scleroderma. However, this study presented “some pretty innovative ways” of measuring whether a patient has gotten appreciably better, he said.

Now that this study has shown the treatment’s effectiveness, Sullivan explained that the next step is to determine the specifics of how stem cell treatment actually works.

“The second goal over the next several years is that with [National Institutes of Health] support, we have been able to collect blood specimens, RNA, cells, serum plasma,” he said. “We have maybe 10 labs and investigators around the country that are now doing mechanistic studies.”

Sullivan also lauded the patients who participated in the studies as being an essential part of the discovery.

“These advances are built upon patients participating in clinical trials, and by that, this is the good news of clinical research, supported by the NIH,” he said. “These discoveries then can be directly applied to individuals across the country to benefit the health of the nation.”