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 U.K., reveals for the first time that the calcium-sensing receptor (CaSR) plays a key role in causing the airway disease.
Using human airway tissue from asthmatic and nonasthmatic people and lab mice with asthma, the researchers demonstrated that manipulating CaSR with an existing class of drugs known as calcilytics reversed all asthma symptoms. They published their findings in the journal Science Translational Medicine.
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.
Dr. 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 percent of health care costs associated with the disease.
Could be treating asthma patients in 5 years, with huge implications for other airway diseases
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, Dr. Riccardi’s team hopes to be testing the drugs on humans within the next 2 years.
“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,” she said.
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), emphysema, and chronic bronchitis. There are currently no cures for these diseases, which current projections indicate will be the third leading cause of death worldwide by 2020.