Future asthma treatment may target trigger allergens

The humble asthma inhaler may be relegated from lifeblood of treatment to a mere backup device if research into allergen delivery inhibitors continues to bear fruit (Photo: Shutterstock)

Asthma attacks are terrifying. They feel almost like the world is closing in around you as you wheeze and cough and gasp for breath. And they often strike suddenly, without warning, when an innocuous event stirs up dust or pollen around you. That terror of unexpected attack that we asthmatics feel every day may largely disappear if a novel new research project pans out. Scientists at the Universities of Cambridge, London, and Manchester have gone after the trigger allergens and developed an inhalable powder from a compound that binds to a major dust mite allergen. This powder could lead to a shift in focus for asthma treatment from relief to inhibition.

House dust mites are sources of more than 20 allergen groups that trigger asthma. The group 1 family of allergens has an especially potent effect on allergic asthma sufferers. These allergens are released into the body by way of inhaled dust mite fecal pellets that release their contents after impact with the airway mucosa (the lining of the airway wall that leads to the lungs). That kickstarts an immune response that ends with the patient's airways being narrowed and partially clogged, leaving them gasping for air.

Traditional asthma medication comes in here. Corticosteroid inhalers, β-agonist bronchodilators, and other steroid or anti-inflammatory drugs used in inhalers and nebulizers relax affected muscles and relieve symptoms so that patients can breathe easily again. But this new approach attempts to cut the allergic reaction off at the pass.

The researchers investigated known inhibitors of Der p 1, a cysteine protease (enzymes that break down proteins) in group 1 of the mite allergens that they explain "is used as a surrogate measure of environmental exposure to house dust mites generally." They then took this as a starting point for an experimental, structure-based drug discovery.

They identified compounds, described as "allergen delivery inhibitors," that were converted into an inhalable powder. That powder was tested on rats, with encouraging results: the rats' immune responses were significantly dampened by the drug when they were exposed to a variety of allergens.

Animal models don't always mimic human responses to asthma drugs, unfortunately, but if further tests succeed, allergen delivery inhibitors could prove a life-changing new approach to treating allergic asthma. Prevention trumps relief of symptoms, and the millions of asthma sufferers with the allergen-triggered variety of the disease may feel that first-hand if the compound flagged for drug development passes evaluation.

A paper describing the research was published in the Journal of Medicinal Chemistry.

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