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Study identifies molecular mechanisms behind AD


According to researchers, abnormalities in the skin barrier and in the immune system that characterize atopic dermatitis can be reversed by drugs that narrowly target the immune signaling proteins interleukin (IL)-4 and -13.

Atopic dermatitis is an immune-driven disease at the molecular level, a new study indicates.

The study, headed by researchers at the Icahn School of Medicine at New York’s Mount Sinai Hospital, was conducted in collaboration with Regenoron Pharmaceuticals, Sanofi and Rockefeller University.

According to a Mount Sinai news release, previous studies have found that drugs that broadly suppress the immune system reduce AD symptoms, but those studies did not describe the molecular mechanisms involved. Some research pointed to genetic orenvironmental factors as being greater contributors to risk.

The current study found that the investigational drug dupilumab (Regeneron Pharmaceuticals), a monoclonal antibody treatment that blocks the action of signaling proteins interleukin (IL)-4 and -13, reversed disease processes seen in the skin at the molecular level. Dupilumab is in clinical trials for several conditions with immune or autoimmune mechanisms.

 “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,” lead author Emma Guttman-Yassky, M.D., associate professor of dermatology at the Icahn School of Medicine, said in a news release,

The release goes on to say that patients treated with dupilumab experienced significant clinical improvements compared with those who were given a placebo. Improvements included reversal of the abnormalities that characterize AD in skin tissues within four weeks of the dupilumab treatment.

According to Dr. Guttman-Yassky, the study is the first involving a drug “that targets specific immune proteins in atopic dermatitis where mechanistic changes track closely with clinical measures of disease and relief from it.”

The researchers say it’s uncertain when phase 3 studies will be completed, but add that new AD drugs should be available in the next few years.

Hamilton JD. Suárez-Fariñaset M, Dhingra N, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 134 ( 6) : 1293 – 1300.



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