A breakthrough study has uncovered a potential root cause of asthma and a drug that reversed symptoms in lab tests. The finding brings hope to the 300 million asthma sufferers worldwide who are plagued by debilitating bouts of coughing, wheezing, shortness of breath and tightness in the chest.
The study – led by Cardiff University in the UK – reveals for the first time that the calcium-sensing receptor (CaSR) plays a key role in causing the airway disease.
The team used human airway tissue from asthmatic and nonasthmatic people and lab mice with asthma to reach their findings.
In the journal Science Translational Medicine, they describe how manipulating CaSR with an existing class of drugs known as calcilytics reversed all symptoms.
Calcilytics block the calcium-sensing receptor and were originally developed for the treatment of osteoporosis – a condition that makes bones more likely to break – also referred to as “brittle bone disease.”
One of the crucial study results is that the symptoms the drug reversed include airway narrowing, airway twitchiness and inflammation – all of which make breathing more difficult.
Daniela Riccardi, principal investigator and a professor in Cardiff’s School of Biosciences, describes their findings as “incredibly exciting,” because for the first time they have linked airway inflammation – which can be triggered for example by cigarette smoke and car fumes – with airway twitchiness. She adds:
“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.”
While the finding is likely to be welcomed by all asthma sufferers, it will particularly excite the 1 in 12 patients who do not respond to current treatments and who account for around 90% of health care costs associated with the disease.
Calcilytics were first developed about 15 years ago for the treatment of osteoporosis, but while they proved safe and well tolerated in trials, results have been disappointing in patients with osteoporosis.
However, the fact they have already been developed and tested gives researchers the unique opportunity to repurpose them and hugely reduce the time it usually takes to bring a new drug to market.
Once funding is secured, the team hopes to be testing the drugs on humans within the next 2 years. Prof. Riccardi concludes:
“If we can prove that calcilytics are safe when administered directly to the lung in people, then in 5 years we could be in a position to treat patients and potentially stop asthma from happening in the first place.”
The researchers believe their findings about the role of CaSR in airway tissue could have important implications for other respiratory conditions such as chronic obstructive pulmonary disease (COPD), chronic bronchitis. There are currently no cure for these diseases, which predictions suggest will be the third biggest killers worldwide by 2020.
In the following video, Prof. Riccardi and colleagues talk about their findings and a patient with asthma describes her excitement about the potential implications.
Asthma UK, the Cardiff Partnership Fund and the Biotechnology and Biological Sciences Research Council (BBSRC) helped finance the study.
Last month, Medical News Today learned of another important study that uncovered new clues about overproduction of mucus in asthma and COPD in the behavior of ion channels – membrane-sited proteins that help regulate the flow of charged particles in and out of cells.
The researchers, from Washington University School of Medicine in St. Louis, believe their findings will lead to treatments for a range of diseases including asthma, COPD, cystic fibrosis and even certain cancers.