Atopic Dermatitis Found To Be an Immune-Driven Disease
For the first time, a team led by researchers at the Icahn School of Medicine at Mount Sinai has proven that atopic dermatitis, also known as eczema, is an immune-driven (autoimmune) disease.
For the first time, a team led by researchers at the Icahn School of Medicine at Mount Sinai has proven that atopic dermatitis, also known as eczema, is an immune-driven (autoimmune) disease at the molecular level. The study, a collaboration with Regeneron Pharmaceuticals, Sanofi and Rockefeller University, was published online earlier this month in the Journal of Allergy and Clinical Immunology.
Past studies had shown that drugs which broadly suppress the immune system reduce symptoms in patients with the disease, but the field had not described in detail the molecular mechanisms involved. Some researchers had argued in the past that genetic or environmental factors were the greater contributors to risk.
In the current study, Emma Guttman-Yassky, MD, PhD, Associate Professor of Dermatology at the Icahn School of Medicine at Mount Sinai and her team of researchers found that dupilumab, a monoclonal antibody treatment that blocks the action of two key signaling proteins, interleukin (IL)-4 and -13,—reversed disease processes seen in the skin of patients at the molecular level. Dupilumab is an experimental drug being development by study partner Regeneron Pharmaceuticals that is currently in clinical trials for several conditions with immune or autoimmune mechanisms.
Interleukins are examples of cytokines, immune proteins that amplify the body’s counteract on invading viruses and bacteria (causing related inflammation), but that can mistakenly target bodily tissues instead as part of autoimmune diseases. Atopic dermatitis is an inflammatory, extremely itchy skin disorder that can cover much of the body in lesions that cause cracks in the skin’s outer barrier, leaving sufferers susceptible to infections.
“Our pioneering study showed that the abnormalities in the skin barrier and in the immune system that characterize atopic dermatitis can be reversed by drugs that narrowly target just these two immune signaling proteins,” said Dr. Guttman-Yassky. In this study, patients treated with dupilumab enjoyed significant clinical improvements compared to those treated with a placebo. These included reversal of the abnormalities that characterize atopic dermatitis in skin tissues within four weeks of the dupilumab treatment.
“This study is the first evaluation of a treatment that targets specific immune proteins in atopic dermatitis where mechanistic changes track closely with clinical measures of disease and relief from it,” said Dr. Guttman-Yassky. “It’s hard to predict how long it may take to complete Phase III studies, but we will probably see new drugs available to treat atopic dermatitis in the next few years.”
As a result of this promising research, the U.S. Food and Drug Administration granted Breakthrough Therapy designation to dupilumab in November 2014 to expedite the development and review of the drug for the treatment of adults with moderate-to-severe atopic dermatitis who are not adequately controlled with topical prescription therapy and/or for whom these treatments are not appropriate.
“Dr. Guttman-Yassky is really changing the world,” said Mark Lebwohl, MD, Sol and Clara Kest Professor of Dermatology and Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai. “She is opening the door to new therapeutic discoveries is helping to improve the quality of lives of patients with eczema,” said Dr. Lebwohl, also president-elect of the American Academy of Dermatology.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.