Researchers at Vanderbilt University Medical Center have developed a new investigational drug that can block inflammatory signaling in a preclinical model of atopic dermatitis – eczema.
Eczema, the most common recurrent inflammatory skin disorder, afflicts an estimated 10 to 20% of children and 5% of adults worldwide, with the highest incidence among African Americans. Symptoms and signs include intense itching, and skin rash with oozing and crusting lesions that can become infected, and which can disrupt sleep and daily activities.
Treatment for severe cases of eczema includes immunosuppressive drugs to control inflammation, monoclonal antibodies that counteract inflammatory proteins called cytokines or their receptors, and antibiotics to fight infection. These treatments will not cure or fully control eczema, however, and some of the drugs can cause significant side effects.
In comparison, the peptide drug developed by the VUMC researchers silenced cytokine-expressing genes, suppressed skin infiltration by inflammatory cells, and healed skin lesions, all without apparent toxicity, at least in the animal model.
“We unraveled the mechanism of eczema by demonstrating that we can control at least 15 genes responsible for the production of the major mediators of skin inflammation,” said the lead investigator, Jacek Hawiger, MD, PhD, Distinguished Professor of Medicine and Louise B. McGavock Professor at VUMC.
Hawiger and his colleagues reported their findings Nov. 7 in the journal Scientific Reports. The topical drug, which is applied directly to inflamed skin, is now being tested in a multicenter clinical trial in patients with eczema.
Hawiger is also a professor of Molecular Physiology and Biophysics at Vanderbilt, and a Health Research Scientist at the Nashville Veterans Affairs Medical Center. Since the mid-1990s, he and his team have been investigating ways to interrupt inflammatory signaling.
The current study of eczema was supported by the Louise B. McGavock Chair, the Immunotherapy Program in the Department of Medicine, the U.S. Department of Veterans Affairs, the National Institutes of Health, and, initially, by Amytrx Therapeutics, a Nashville-based company Hawiger cofounded in 2014 to sponsor clinical trials of the drug.
In addition to Hawiger and his scientific partner, Jozef Zienkiewicz, PhD, Research Professor of Medicine, co-authors of the paper were Yan Liu, MD, Huan Qiao, MD, PhD, Katherine N. Gibson‑Corley DVM, PhD, Kelli L. Boyd DVM, PhD, and Ruth Ann Veach, BS.
Journal
Scientific Reports
Article Title
Genomic control of inflammation in experimental atopic dermatitis
Article Publication Date
7-Nov-2022