Cure for asthma on horizon as scientists find genetic cause 

A boy uses an inhaler
Asthma could be prevented with a drug to block gene activity 

A cure for asthma is on the horizon after scientists discovered a genetic switch which prevents the condition.

The research carried out at the University of Southampton, discovered that the gene ADAM33 plays a crucial role in causing the twitchiness and inflammation of airways that triggers an attack.

The gene makes an enzyme which usually attaches to the muscles in the airways helping to repair and regenerate damaged areas.

But the enzyme can become detached and 'go rogue' travelling around the lung and sparking the unnecessary production of new muscles and blood vessels which cause the airways to narrow – a process known as airway remodelling.

Scientists traditionally through that it was allergens – like pollen - that triggered airway remodelling, inflammation and eventually asthma attacks. But they could never explain why lots of people with allergies never get asthma.

Now scientists believe that it takes the combination of the rogue gene and an allergen to trigger an attack.

Studies in human tissue samples and mice showed that if the gene is switched off allergens do not have the same impact on the airways. 

Prof Hans Michel Haitchi, associate professor in respiratory medicine, said: “This finding radically alters our understanding of the field, to say the least.

“For years we have thought that airway remodelling is the result of the inflammation caused by an allergic reaction, but our research tells us otherwise.”

Around 5.4 million people in Briton suffer from asthma, but the new study suggests that drug to knock out the effects of the ADAM33 gene could prevent attacks.

The team at Southampton has already identified molecules which can switch off both gene itself, and the enzymes.

They are planning to test the new medication in mice and are already in talks with pharmaceutical companies to bring the treatment to market. Charity Asthma UK has also agreed to help fund the next stage describing the breakthrough as 'promising.'

A rogue enzyme is thought to be responsible for ashthma 
A rogue enzyme is thought to be responsible for ashthma 

The treatment could be taken daily as a pill, inhaled or even injected monthly to prevent attacks ever happening.

Experiments in mice have shown that inflammation dropped by 50 per cent in asthma-prone mice who had their ADAM33 gene removed when exposed to a house dust mite allergen.

Prof Haitchi, whose research was primarily funded by a Medical Research Council Clinician Scientist Fellowship, said: "Our studies have challenged the common paradigm that airway remodelling in asthma is a consequence of inflammation.

"Instead, we have shown that rogue human ADAM33 initiates airway remodelling that promotes allergic inflammation and twitchiness of the airways in the presence of allergen.

"More importantly, we believe that if you block ADAM33 from going rogue or you stop its activity if it does go rogue, asthma could be prevented.

"ADAM33 initiated airway remodelling reduces the ability of the lungs to function normally, which is not prevented by current anti-inflammatory steroid therapy.

"Therefore, stopping this ADAM33-induced process would prevent a harmful effect that promotes the development of allergic asthma for many of the 5.4 million people in the UK with the condition."

Dr Samantha Walker, Asthma UK’s Director of Research and Policy, said: “This is a really promising avenue of research that we have already agreed to help fund to its next stage, which is to understand exactly how this gene causes the changes seen in the lungs that lead to asthma.

This will hopefully bring us even closer to stopping asthma attacks and finding a cure for the one in 11 people with asthma in the UK.

“Each day three people die of asthma attacks. Research like this is a step in the right direction although much more investment is needed.

"There are hundreds of thousands of people in the UK for whom current treatments don’t work and they struggle to breathe every day. Research like this will give us better avenues to explore why this is the case and to develop treatments that work.”

The research was published in The Journal of Clinical Investigation Insight.

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