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Switching off rogue gene could prevent asthma

25 July 2016
Appeared in BioNews 861

A gene involved in the muscles of the respiratory system may be the trigger for asthma, according to a study.

The researchers have suggested a new model of how asthma develops, and they believe it could lead to preventative treatments for the disease.

'This finding radically alters our understanding of the field, to say the least,' said Dr Hans Haitchi of the University of Southampton, who led the research.

His group have been investigating the role in asthma of a gene called ADAM33, which codes for an enzyme normally found attached to the surface of airway muscle cells. In people with asthma this enzyme can become detached and go 'rogue', they say.

'We believe that if you block ADAM33 from going rogue, or you stop its activity if it does go rogue, asthma could be prevented,' said Dr Haitchi.

The researchers found that high levels of detached ADAM33 protein can cause the growth of new muscle and blood vessels in the lungs, even though they aren't needed. This process is called 'airway remodelling' and is a key feature of asthma.

Traditionally, it is thought that airway remodelling is triggered by exposure to allergens causing inflammation of the lungs and asthma symptoms. This new research challenges that model.

The group also found that airway remodelling was reversed in mice that had ADAM33 switched off. Inflammation decreased by 50 percent when the gene was switched off in asthma-prone mice that were exposed to house dust mite allergen. And experiments in human tissue samples showed that switching off the ADAM33 gene could also significantly reduce inflammation caused by allergens.

They conclude that a combination of airway remodelling and allergen exposure together promote asthma attacks.

'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,' said Dr Haitch.

The researchers say that ADAM33 could be a target for developing drugs to prevent asthma instead of just treating the symptoms, as most current therapies do. The group has already identified molecules that can switch off both the gene itself and the enzyme it codes for.

Dr Samantha Walker, director of research and policy at Asthma UK, said: 'This is a really promising avenue of research. 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.'

Asthma cure could be developed in next 5-10 years
News Talk |  22 July 2016
Asthma cure on the horizon, according to University of Southampton study
The Independent |  21 July 2016
Cure for asthma on horizon as scientists find genetic cause
The Telegraph |  21 July 2016
Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life
JCI Insight |  21 July 2016
Stop the rogue ADAM gene and you stop asthma
Eureka Alert (press release) |  21 July 2016
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