Genetic switch 'could pave the way towards preventing asthma'

Scientists have discovered a genetic switch which could pave the way for preventing asthma at the origin of the disease.

The research carried out at the University of Southampton, published in The Journal of Clinical Investigation (JCI) Insight, analysed the impact of the gene ADAM33, which is associated with the development of asthma.

ADAM33 makes an enzyme, which is attached to cells in the airway muscles.

When the enzyme loses its anchor to the cell surface, it is prone to going rogue around the lung causing poorer lung function in people who have asthma.

The studies in human tissue samples and mice, led by Hans Michel Haitchi, associate professor in respiratory medicine, suggests that if you switch off ADAM33 or prevent it from going rogue, the features of asthma - airway remodelling (more muscle and blood vessels around the airways), twitchiness and inflammation - will be reduced.

Prof Haitchi 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."

The first study showed that rogue human ADAM33 causes airway remodelling resulting in more muscle and blood vessels around the airways of developing lungs, but it did not cause inflammation.

When a house dust mite allergen was introduced, which is a common human allergen, both airway remodelling and allergic airway inflammation were more significantly enhanced.

In another study, remodelling of the airway was shown in mice that had ADAM33 switched on in utero.

The gene was then switched off and the airway remodelling was completely reversed.

They also studied the impact of house the dust mite allergen on asthma features in mice which had the ADAM33 gene removed.

Airway remodelling and twitchiness as well as airway inflammation rates were significantly reduced by 50% and respectively 35% in mice which did not have the rogue gene.

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."