Cellular gatekeepers could unlock new asthma and allergy treatments
Asthma and other allergic reactions are increasingly common today, and while manageable there’s currently no cure. Now, researchers at Yale University have found a new potential pathway for treatment, targeting cellular "gatekeepers" called microRNA.
Asthma is a common condition usually triggered when the body overreacts to irritants, causing excessive inflammation of the airways that makes it difficult to breathe. Allergies work in a similar way, with that inflammation affecting the sinuses and causing rhinosinusitis, a condition characterized by congestion and runny noses.
In previous studies, the Yale team found that the problem starts in endothelial cells. These cells line the blood vessels in the nose and lungs, and in people with asthma and rhinosinusitis, they tend to let in too many eosinophils. These are immune cells that, in high numbers, trigger the unwanted inflammation.
“We asked: ‘What if we could stop these blood cells at the gate?’” says Shervin Takyar, lead researcher on the study. “There’s a difference in the cellular language between people who naturally let eosinophils into their lungs and people who naturally don’t. We wanted to understand the language of the cells of these healthier people.”
For the new study, the team singled out one particular microRNA, known as miR-1. This molecule acts as a kind of gatekeeper that restricts eosinophils from getting into the blood vessels of the lungs and nasal passages. As such, lower levels of miR-1 leads to higher inflammation and other symptoms of asthma and allergies. The researchers demonstrated this with samples of human lung and sinonasal tissue.
To test whether this could be a treatment target, the team then experimented with mice by administering miR-1 into their nasal passages. They found that this successfully altered the levels of the microRNA in their blood vessels, and improved their symptoms. Eosinophil levels dropped by half, and airway and lung inflammation, mucus levels and other asthma symptoms were all reduced.
Tests on human blood vessels also showed promise. The team says that the molecule reduced the amount of eosinophils entering tissues, which could open a door to new treatments for patients who haven’t found relief with existing medications.
“Here is a new language,” says Takyar. “We’re getting in line with how cells talk and using their language to close gateways, and we expect to see real improvements in severe asthma and allergy patients.”
The research was published in the Journal of Allergy and Clinical Immunology.
Source: Yale University