2.7 million Australians could breathe more easily: treating asthma without increasing vulnerability to infection

Treatment for asthma might take a new direction with scientists finding a class of drugs which don’t suppress the immune system’s response to infections like Influenza A.

According to the latest data from the Australian Bureau of Statistics, just under 2.7 million (10.7%) of Australians had asthma in 2020-21, with one third of sufferers using daily medication.

Treatments for allergic asthma – where lungs become inflamed due to allergens such as dust mite faeces – is often via medicines which suppress the immune system which can result in an increased susceptibility to infections such as influenza.

An international group of medical researchers has been investigating a new type of drug called a ‘calcium release-activated calcium channel inhibitor’, (CRAC). This compound blocks the action of calcium signals in immune cells and, in mice lungs, dramatically reduces inflammation and mucus accumulation when exposed to dust mite faeces.

“Our study provides evidence that a new class of drugs that target CRAC channels can be used safely to counter allergic asthma without creating vulnerability to infections,” says senior study author Dr. Stefan Feske the Jeffrey Bergstein Professor of Medicine in the Department of Pathology at NYU Langone Health.

Allergic asthma is the result of an inappropriate inflammatory response to an irritant. For instance, when an asthmatic, who is allergic to dust mite faeces, breathes them in, cytokines are produced by a special subset of T immune cells known as T helper (Th) 2 cells. These cytokines are small proteins that aid in cell-to-cell messaging in immune responses, for example when the body needs to communicate to fight an infection.

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In allergic asthma responses, however, these cytokines promote the production of an antibody called IgE and encourage immune cells, called eosinophils, to head to the lungs where they cause inflammation resulting in wheezing, breathlessness, chest tightness and coughing.

In mice, the CRAC inhibitor, known as CM4620, worked to stop calcium entering the CRAC channels. This in turn stopped the T cells becoming Th2 cells, halting the production of cytokines and subsequent inflammation.

By investigating the immune response to Influenza A viruses in their mouse models , the researchers were able to show that the CRAC inhibitor did not compromise immunity to infection – a key concern for developing effective asthma therapeutic treatments.

Co-first author Yin-Hu Wang, PhD, a post-doctoral fellow in the Feske lab, is positive about the new drug’s potential impact: “This suggests CRAC channel inhibition as a promising, potential future treatment approach for allergic airway disease.”