The first new asthma treatment in decades could be on the horizon after the discovery of a protein which prevents the condition, according to experts.
The key chemical, a muscle relaxant, is missing from sufferers - triggering airway constriction, mucus, chest tightness and breathing problems.
Now scientists believe they could develop a pill or inhaler which would restore the protein relieving symptoms for five million asthmatics in the UK and 334 million worldwide.
The protein, known as SPLUNC1, was originally identified for its role in cystic fibrosis by Professor Robert Tarran, whose colleague Prof Steve Tilley then wondered if it was involved in asthma.
So they measured levels in samples obtained from patients and healthy volunteers in the Centre for Environmental Medicine, Asthma, and Lung Biology at the University of North Carolina.
Prof Tilley said: “We were astonished to find SPLUNC1 levels were markedly reduced in people who have asthma.”
His lab found the protein was also depleted in asthmatic mice. Restoring it reversed airway hyper responsiveness, a cardinal feature of asthma making it difficult to breath.
Prof Tarran found SPLUNC1 could regulate contraction of the airway smooth muscle by blocking calcium, providing an explanation of how a deficiency may lead to the symptom.
He said: “People have been studying SPLUNC1 and its role in the context of other diseases, such as cystic fibrosis and lung cancer, but we believe we are the group to identify its role in asthma.”
The protein is produced by the outer, or epithelial, cells that line the airways, reports Nature Communications.
Prof Tarran said: “We found this protein, which is actually turned off by excessive inflammation, is needed to cause the muscle to relax.
“It is essentially a muscle relaxing factor that is missing from asthma patients. It is something that normally acts as a brake.”
A potential therapy would be to replenish either the whole protein or part of it, which could be delivered by an inhaler.
Explained Prof Tarran: “Instances of asthma are much higher in the western world.
“Some of the highest countries are Australia, the UK and the States. The cost of asthma to the healthcare system in the US is quite big.
“Most of the asthma therapies people use are inhalers, which have been around for decades.
“There have only been a few new asthma medications in the past 10 or 20 years, and they are still being evaluated.
“This protein could be a potentially new target to go after, and it could really benefit a lot of people.”
The crystal structure of SPLUNC1, which was key in developing the next steps of the research, was identified by their microbiologist colleague Prof Matt Redinbo.
Prof Tarran said: “Since we know the crystal structure of the protein, we are able to find the active site of the protein that regulates smooth muscle contraction. So we can make peptides or drugs to target that active site and see if that works. That is one approach.
“We want to study this in patients to correlate SPLUNC1 levels with airway hyper-reactivity.
“And we also want to go deeper into the mechanism - how does this protein do what we observed. So there are several future avenues of research: expanding clinical studies, designing drugs in mouse studies, and then studying the underlying biology of what happens in a person with asthma.”
Prof Tilley, who has been researching asthma for the past 20 years, said the SPLUNC1 observation and its potential to reverse airway hyper-responsiveness was “the most exciting discovery I have been involved with.”
He added: “If we can further establish SPLUNC1 is the elusive epithelial derived relaxing factor that is deficient in asthmatics, then we can begin working on ways to restore SPLUNC1 levels in patients as a novel therapy to treat asthma.
“I am looking forward to working with Drs. Neil Alexis, Ilona Jaspers, and David Peden in our asthma centre to design more translational studies in humans so we can determine the clinical significance and therapeutic potential of SPLUNC1 in asthma.”
The results offer real hope for the 5.4 million people in the UK who have the condition.
Three people die every day because of asthma attacks - two of which are preventable, previous research found.
Half of the UK will suffer from hay-fever, asthma or some kind of allergy by 2026 if current trends continue.