Asthma breakthrough by Cardiff researchers


Root cause discovery and potential for new treatment

Cardiff university researcher’s may have found the root cause for asthma and are testing a drug that could stop it.

Published in journal Science Translational Medicine this month, researchers at the School of Biosciences, along with collaborators at King’s College London and the Mayo Clinic in the USA have results that are “incredibly exciting”.

Asthma affects over 5.4 million people in the UK, and last year 314,000 people sought medical intervention in Wales for the disease. The NHS spends over £1 billion a year, and while it is controllable for most sufferers, asthma kills three people per day in the UK. Symptoms include wheezing, coughing and tightness in the chest due to the narrowing of the airways, often caused by environmental triggers.

Asthma varies in severity, and when it affects 1 in 10 people across Wales, it is no surprise that many university students suffer too. Third year student Greg McChesney said, “While my form of asthma is relatively minor and fairly easily managed, it is prone to flaring up during the winter months, Any contact with very cold or dusty air can trigger a tightening feeling in your chest and difficulty breathing normally, like there’s a weight on your chest. A few years ago after swimming in very cold water I suffered a mild asthmas attack, and while I didn’t need to be hospitalised it was still an alarming situation to be in.”

The latest research paper from Cardiff describes that while most traditional treatments such as corticosteroids and bronchodilators – those brown and blue inhaler pumps – work for most sufferers, a “significant minority of patients whose symptoms fail to be controlled” remain, “who face chronically impaired quality of life with increased risk of hospital admission and even death.”

According to Professor Danielle Riccardi of the School of Biosciences, principal investigator of the study, “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 care fumes – and airways twitchiness in allergic asthma.”

By studying mouse models of asthma, as well as human airway tissue from healthy and ill patients, researchers have proved the role of a calcium sensing receptor in causing the disease, known as CaSR. Riccardi said, “Our paper shows how these triggers release chemicals that activate CaSR in airway tissue and drive asthma symptoms like airway twitchiness, inflammation, and narrowing.” The study showed that asthmatic patients and mice express much more of the CaSR receptor than their healthy counterparts, indicating an important role in the disease.

The group have also looked in depth at a class of drugs called calcilytics in treating the condition. Originally targeted for use in osteoporosis over 15 years ago, these drugs target the CaSR receptor to induce hormone release. However, efforts to treat bone thinning failed, and now repurposing the drug might be the answer for difficult-to-treat asthma cases. “Using calcilytics, nebulized directly into the lungs, we show that it is possible to deactivate CaSR and prevent all of these symptoms,” Riccardi added. The drug appears to reduce airway hyper responsiveness and inflammation in the mice that were tested.

The way forward is to now seek more funding, to determine the effectiveness of this type of drug in severe cases of asthma, and trial on humans within two years. Riccardi said, “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.”

Samantha Walker of Asthma UK, a charity that helped fund the research, said: “Five per cent of people with asthma don’t respond to current treatments so research breakthroughs could be life changing. If this research proves successful we may be just a few years away from a new treatment for asthma, and we urgently need further investment to take it further through clinical trials.”

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