MUSC Leads Research on Potential Lupus Treatment

Dr. Kamen with a patient
Diane Kamen, M.D., examines a patient.

Systemic lupus causes the body’s immune cells—the defense system that usually protects against disease—to attack the body’s own tissues and organs such as the kidneys. Lupus kidney disease is more prevalent and severe in women who are African American or Hispanic.

Why that is the case is just one question researchers at MUSC and elsewhere are pursuing, along with the goal of developing better treatments to prevent the need for transplants.

Researchers in the Department of Medicine’s Rheumatology Division hope a five-year, $3.8 million grant from the Lupus Foundation of America, that was awarded in November 2017, will help shed light on that question. This grant provides funding for a phase 2 clinical trial that will evaluate an extremely novel treatment using mesenchymal stem cells harvested from donated umbilical cords in patients with lupus resistant to treatment.

The study, led by the Medical University of South Carolina’s Gary Gilkeson, M.D., and Diane Kamen, M.D., marks a milestone in lupus research, which has only had one drug developed specifically for lupus and approved by the U.S. Food and Drug Administration. The National Institutes of Health is partnering in this study, granting $3.5 million additional dollars over five years to determine how the stem cells are affecting lupus.

More treatment options for lupus are needed, given the number of people affected by this chronic autoimmune disease that can damage any part of the body, including the skin, joints, and organs, says Gilkeson. More than 16,000 new cases of lupus are reported each year, and women of color are two to three times more likely to develop it.

“The severity is worse in African Americans and Hispanics, although the severity in Hispanics varies depending on their family origin, specifically Central America versus Puerto Rico versus Spain,” says Kamen.

According to Gilkeson, anywhere from 40 to 60 percent of blacks and Hispanics will develop kidney damage from lupus. The rate of their progression to renal failure is five to 10 times that of whites, even when given the same treatments. “They progressively have more decline over time. This progression appears to be genetically linked.”

The idea for using mesenchymal stem cells was planted seven years ago when Gilkeson went to China and learned of the work of Lingyun Sun, M.D., Ph.D., of the Affiliated Drum Tower Hospital of Nanjing University Medical School, a sister hospital of MUSC Health. “Dr. Sun presented his work, and it was very intriguing, so we started working with him. It’s taken almost 10 years to get to this point, but the therapy shows promise,” Gilkeson says.

In FY18, MUSC’s Division of Rheumatology was also awarded a comprehensive clinical center of research infrastructure grant from the National Institutes of Health for $750,000 a year for five years, one of only three such centers in the country. This grant supports studies to determine why African Americans have more prevalent and severe lupus and scleroderma than other ethnicities.

MUSC’s Center for Cellular Therapy houses an FDA-registered cGMC facility approved to manufacture cells for human therapeutic use. There are only 15 such centers in the country, and the existence of this center at MUSC was a necessity for the funding of this project. The center will provide the mesenchymal stem cell therapy for all seven medical facilities involved with the trial.

“The stem cells don’t carry immune markers on them, allowing us to give cells from an unrelated donor to lupus patients. About 15 patients can be treated with cells from one cord,” says Gilkeson. “We don’t know exactly how they work, but we know they suppress the immune system and cause profound changes on the immune parameters. They reduce the abnormal reactions of the patients’ systems attacking themselves.” The NIH grant will provide the funding to identify how the cells work.

Drs. Kamen and Gilkeson
(L-R): Diane Kamen, M.D., and Gary Gilkeson, M.D.

Early responses in six patients treated in the phase 1 trial are encouraging, with five patients who had not responded to standard lupus therapies improving in their lupus symptoms after receiving the therapy. All patients are aware they are getting the cells, and no patients experienced adverse reactions, says Gilkeson.

The expansion of the phase 2 trial is now underway and will enroll 81 people with lupus who are not responding well to current treatments. The trial is expected to last through June 2022, with the five patients enrolled in the first month the trial was open. The trial will expand to seven additional academic centers in Atlanta, Chapel Hill, Chicago, Los Angeles, Rochester, and San Diego, with MUSC being the lead center.

Over a hundred patients have reached out to see if they can be part of the study.

Though more study is needed on why it works, it seems that the mesenchymal stem cell treatment activates T-regulatory cells, which modulate the immune system and occur in lower amounts in lupus patients. It also seems to knock out double negative B cells, or B cell lymphocytes, a type of white blood cell that is increased in lupus, to get them to a normal level, says Gilkeson.

“It doesn’t work for everyone, but there are encouraging results overall,” Gilkeson says, adding that other researchers are exploring this technique for wound healing, bone grafting, graft-versus-host disease, kidney transplants, and islet cell transplants.

Gilkeson, who has studied lupus for more than two decades, says he’s grateful for the funding that will determine whether this novel therapy will be a game changer for lupus treatment. He sees the toll the disease can take. The Lupus Foundation of America was the first organization to see the potential for stem cell treatment in people with lupus and over the past 10 years provided funding of $1.2 million to researchers at multiple institutions to explore its utility.

Though it can affect men and women at any age, it tends to occur in young women. “It’s compelling to me because it is so common in young women in their 20s who are just starting out in their careers and their families,” Gilkeson says. “It’s a serious disease that can be life threatening. We have some treatments, but we need better therapies. With this new treatment, our goal is to allow them to lead normal lives.”

Original article by Dawn Brazell, MUSC Catalyst News.