Preventing Asthma: Research linked to stopping the rogue gene ADAM33
Scientists at the University of Southampton have discovered a potential and novel way of preventing asthma at the origin of the disease, a finding that could challenge the current understanding of the condition.
The research, published in The Journal of Clinical Investigation (JCI) Insight, analyzed 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 carried out at the university suggests that switching off ADAM33 or prevent it from going rouge, leads to the reduction of asthma symptoms.
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, both, airway remodelling and allergic airway inflammation increased.
In another study, remodelling of the airway was shown in mice that had ADAM33 switched on from in utero.
When gene was then switched off and the airway remodelling was completely reversed.
The study also demonstrated that airway remodelling, twitchiness and airway inflammation plummeted by 50 per cent and respectively 35 per cent in mice that did not have the rogue gene.
The findings identify ADAM33 as a novel target for disease modifying therapy in asthma.
Professor 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.”