SYM-2081

THURSDAY, Dec. 12, 2024 -- It's still early science -- studies in mice and in human cells -- but researchers are on the trail of an effective new treatment for inflammatory skin conditions such as rosacea . Skin cells called mast cells are key players in the inflammation and itchiness that can plague folks with these skin ailments. However, researchers at the University of Pittsburgh report they've spotted a compound called SYM2081 that can quiet down these overactive cells. “I’m really excited about the clinical possibilities of this research,” said senior study author Dr. Daniel Kaplan , a professor of dermatology and immunology at the university. “Currently, there aren’t a lot of good therapies that target mast cells, so we think that our approach could potentially have huge benefits in many skin conditions, including rosacea, eczema, urticaria [hives] and mastocytosis [a rare genetic disorder that causes the body to produce too many mast cells].” His team published its findings Dec. 11 in the journal Science Translational Medicine . Anyone with hay fever or other allergies has heard of histamines; cellular compounds that can trigger or signal the misery of inflammation. According to Kaplan's team, mast cells contain "granules" loaded with histamines (and other pro-inflammatory agents). When these granules tear open, that can trigger a cascade of inflammatory immune responses such as those seen in rosacea or eczema. Granule rupture is beneficial when the threat to the skin is real and a quick immune response is needed -- a bee sting, for example. However, out-of-control granule rupture and histamine activity is at the root of allergic reactions like swelling, hives and itchiness, the researchers explained. Kaplan's team had already discovered that mast cells can recognize a compound called glutamate, which appears to keep the cells from going into overdrive. When they "switched off" the mast cell receptor that was targeted to glutamate, mast cells became hyperactive. “This finding led us to wonder if doing the opposite would have a beneficial effect,” Kaplan said in a university news release. “If we activate the glutamate receptor [Gluk2], maybe we can suppress mast cell activity and inflammation.” The newly discovered compound, SYM2081, appears to do just that. In experiments conducted in mice and in human cells, SYM2081 activated the glutamate receptor on mast cells, quieting things down. For example, mice prone to rosacea- or eczema-like symptoms had much milder outbreaks of the disease if they had been treated with a cream containing SYM2081, Kaplan's team found. Rosacea is a common skin malady characterized by a thickening of the skin, pimples, broken blood vessels and facial redness. Could treating rosacea with an SYM2081-bearing cream ease inflammation, itchiness and swelling in people, as well? That remains to be seen, the team said. “Although there are excellent therapies available for different types of rosacea, many are antibiotic-based and they only target some of the symptoms,” Kaplan noted. “There are no good therapies for [rosacea-linked] flushing, so this is a significant unmet need. Our study suggests that suppressing mast cells by activating GluK2 could reduce the flushing associated with rosacea.” The new study was funded by the U.S. National Institutes of Health. Kaplan's team has already applied for a patent for the potential new therapy, and clinical trials in patients are planned. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.