This new substance may one day stop serious inflammatory reactions (such as IBS and asthma)

Mast cells are part of our immune system that protect our bodies from viruses, bacteria, and even harmful substances released by snakes and insect bites. When alerting for the presence of such invaders, mast cells produce mucus, trigger swelling and itching, and cause muscles to contract in our airways, stomach, and intestines. Although these symptoms allow the body to destroy or expel invaders, overly sensitive mast cells can cause allergic reactions, including life-threatening and difficult to deal with.

As detailed in a study published Monday in the Journal of Signal Transduction and Targeted Therapy, researchers have developed a compound that prevents mast cells from triggering particularly difficult, sometimes life-threatening responses. These include irritable bowel syndrome (IBS), asthma, chronic itching, and migraine. The pseudo-allergic reactions to these diseases have been traditionally thought to have been classified as an allergic recently, researchers say. The compound appears to significantly alleviate symptoms and therefore reduce the risk of death.

“So we think it's a very promising substance,” Christa Müller, co-author of the study, who studied membrane protein chemistry at the University of Bonn, said in a university statement.

Unlike some allergic reactions, where immune cells called antibodies remind the mast cells of the presence of the invader, these difficult-to-treat conditions occur through direct activation triggered by direct activation without the involved antibody. This triggered “a response of a specific nature that has been difficult to treat until today,” Müller explained.

15 years ago, Müller and colleagues identified a receptor called MRGPRX2 on the membrane of mast cells, which “opened” these reactions when certain molecules attached to it. “To prevent this reaction, the switch must be blocked in some way.” “The question is: How?”

To address this, the team tested the promising compounds collected by the Mueller department previously collected by 40,000 of them. “We used cells that light up when MRGPRX2 is activated, so we can test whether the substance is effective in blocking the activation of the receptor and turning off the light signal,” explains Müller's doctoral student Ghazl Al Hamwi, the first author of the study. In this way, the team discovered a molecule that can connect to the receptor and block it, effectively shutting it off.

They used the molecule to develop a substance that is still very low-dose and demonstrated its efficacy in eliminating life-threatening allergic reactions in laboratory mice and preventing MRGPRX2 receptors on isolated human mast cells. They also claimed that the molecule blocked only the expected receptor, thus avoiding the risk of side effects.

Although Al Hamwi, Müller and colleagues have since improved the efficacy and duration of the substance, more animal and human trials must be conducted for approval and commercialization as a drug. However, it has potentially life-saving effects on patients with certain inflammatory diseases and the risk of allergic shock.