A new way to treat common inflammatory skin conditions such as eczema is on the horizon, according to a new study.
American researchers found that a compound called SYM2081 inhibited certain cells responsible for inflammation in mice and human skin samples.
They say this opens the door to new treatments to prevent itching, hives and other symptoms of skin conditions, such as eczema and rosacea, caused by mast cells.
Rosacea is a long-term skin condition that primarily affects the face. This can cause acne-like pimples, broken blood vessels, thickening of the skin, and facial redness.
“I’m really excited about the clinical possibilities of this research. » said study lead author Professor Daniel Kaplan of the University of Pittsburgh. “Currently, there aren’t many good treatments targeting mast cells, so we think our approach could potentially have huge benefits in many skin conditions, including rosacea, eczema, urticaria and mastocytosis. “
He explained that mast cells are filled with tiny granules “brimming” with histamine and other compounds that act as signals or activators of inflammatory pathways. When mast cells are activated, the granules open, releasing compounds that trigger a series of immune responses.
Kaplan says the process, known as degranulation, is essential for protection against threats such as bee venom, snake bites and pathogenic bacteria, but erroneous activation of mast cells also triggers allergic reactions, including swelling, hives, itching and, in severe cases, anaphylaxis, depending on the published results in the journal Science Translational Medicine.
In a previous paper, Kaplan and his team discovered that neurons in the skin release a neurotransmitter called glutamate that suppresses mast cells. When they suppressed neurons or inhibited the receptor that recognizes glutamate, mast cells became hyperactive, leading to more inflammation.
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“This finding made us wonder whether doing the opposite would have a beneficial effect,” he said. “If we activate the glutamate receptor, we may be able to suppress mast cell activity and inflammation.”
To test this hypothesis, the research team looked at a compound called SYM2081, or 4-methylglutamate, which activates a glutamate receptor called GluK2 that is found almost exclusively in mast cells.
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They found that SYM2081 effectively suppressed mast cell degranulation and proliferation in both mouse and human skin samples. When mice were given a topical cream containing SYM2081 before the induction of rosacea or eczema-like symptoms, skin inflammation and other symptoms of the disease were much milder.
A daily cream containing a GluK2 activating compound could therefore be a promising way to prevent rosacea and other inflammatory skin conditions.
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“While there are excellent treatments available for different types of rosacea, many are antibiotic-based and only target certain symptoms. There are no good treatments for rash, so this is a significant unmet need,” Kaplan said.
Now that the research team has demonstrated proof of concept for their approach, they hope to design new GluK2 activating compounds that could eventually be tested in clinical trials.
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