Researchers have described the role of the calcium sensing receptor (CaSR) in causing asthma, a disease which affects 300 million people worldwide, by using mouse models of asthma and human airway tissue from asthmatic and non-asthmatic people.
Their paper in Science Translational Medicine highlights the effectiveness of a class of drugs known as calcilytics in manipulating CaSR to reverse all symptoms associated with the condition. These symptoms include airway narrowing, airway twitchiness and inflammation - all of which contribute to increased breathing difficulty.
Calcilytics were first developed for the treatment of osteoporosis around 15 years ago with the aim of strengthening deteriorating bone by targeting CaSR to induce the release of an anabolic hormone. Although clinically safe and well tolerated in people, calcilytics proved unsuccessful in treating osteoporosis. While asthma is well controlled in some people, around one-in-twelve patients respond poorly to current treatments. This significant minority accounts for around 90% of health care costs associated with the condition.
According to Cardiff University Professor Paul Kemp, who co-authored the study, the identification of CaSR in airway tissue means that the potential for treatment of other inflammatory lung diseases beyond asthma is immense. These include chronic obstructive pulmonary disease (COPD) and chronic bronchitis, for which currently there exists no cure. It is predicted that by 2020 these diseases will be the third biggest killers worldwide.
"Our findings are incredibly exciting," said principal investigator Professor Daniela Riccardi from Cardiff University School of Biosciences. "For the first time we have found a link between airways inflammation, which can be caused by environmental triggers - such as allergens, cigarette smoke and car fumes - and airways twitchiness in allergic asthma. Our paper shows how these triggers release chemicals that activate CaSR in airway tissue and drive asthma symptoms like airway twitchiness, inflammation, and narrowing. Using calcilytics, nebulized directly into the lungs, we show that it is possible to deactivate CaSR and prevent all of these symptoms."
This breakthrough provides researchers with the opportunity to re-purpose those drugs.
"If we can prove that calcilytics are safe when administered directly to the lung in people, then in five years we could be in a position to treat patients and potentially stop asthma from happening in the first place," added Riccardi.