New study to target asthma gene

Researchers from the Faculty of Medicine are to begin a new study testing a new class of drugs that target the asthma gene ADAM33.

Asthma is a common respiratory disease, but no current treatment targets the underlying cause of airway remodelling and associated bronchial hyperresponsiveness (BHR) that happens due to the condition.

The ADAM33 gene is associated with BHR and asthma. The membrane-anchored protein is expressed in airway fibroblasts and smooth muscle, but an enzymatically active soluble form (sADAM33) is upregulated in the airways by gain of function in patients with asthma.

Previous research from the Faculty has shown that the remodelling is reversible on arrest of sADAM33, and Adam33 knock-out suppresses airway remodelling, BHR and inflammation making it a possible target for a disease modifying asthma therapy.

In a new study, with Jonathan K Watts from the University of Massachusetts, the Southampton group, led by Dr Hans Michael Haitchi, Associate Professor in Respiratory Medicine, will test a potent ADAM33 silencing oligonucleotides that they developed.

Dr Haitchi said: “We believe that our ADAM33 specific oligonucleotides will allow us to target characteristics of the disease which are not treated by current asthma drugs. Thus, our aim is to develop a new disease-modifying asthma therapy that helps patients whose asthma doesn't respond to currently available medicines.”

Other collaborators include Professor Christian Ottensmeier, chief investigator of “TargetLung” from University of Liverpool and Mr Aiman Alzetani, thoracic surgeon at University Hospital Southampton. The study is being funded by a UKRI grant from the Medical Research Council – Developmental Pathway Funding Scheme.