A team of scientists has for the
first time identified the potential root cause of asthma and an
existing drug that offers a new treatment.
The work was carried out by
researchers from King's College London, Cardiff University and the
Mayo Clinic in Minnesota, USA. The researchers describe the
previously unproven role of the calcium sensing receptor (CaSR) in
causing asthma, a disease which affects 300 million people
worldwide.
The team, which includes Professor
Christopher Corrigan and Professor Jeremy Ward from the Division of
Asthma, Allergy and Lung Biology at King's College London, used
mouse models of asthma and human airway tissue from asthmatic and
non-asthmatic people to reach their findings.
Crucially, the paper 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.
"Our findings are incredibly
exciting," said Professor Daniela Riccardi of Cardiff University.
"For the first time we have found a link 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, nebulised directly into the lungs, we
show that it is possible to deactivate CaSR and prevent all of
these symptoms."
Dr Samantha Walker of Asthma UK
said: "This hugely exciting discovery enables us, for the first
time, to tackle the underlying causes of asthma symptoms. Five per
cent of people with asthma don't respond to current treatments so
research breakthroughs could be life changing for hundreds of
thousands of people.
"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. Asthma research is chronically underfunded; there
have only been a handful of new treatments developed in the last 50
years so the importance of investment in research like this is
absolutely essential."
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 healthcare costs associated with the condition.
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.
The team is now seeking funding to
determine the efficacy of calcilytic drugs in treating asthmas that
are especially difficult to treat, particularly steroid-resistant
and influenza-exacerbated asthma, and to test these drugs in
patients with asthma.
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.
But this latest breakthrough has
provided researchers with the unique opportunity to re-purpose
these drugs, potentially accelerating the time it takes for them to
be approved for use asthma patients. Once funding has been secured,
the group aim to be trialling the drugs on humans within two
years.
"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
Professor Riccardi.
The paper, Calcium-sensing receptor antagonists abrogate airway
hyperresponsiveness and inflammation in allergic asthma, is
published in Science Translational
Medicine.