Genetically tailored therapy marks adolescent asthma breakthrough

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RESEARCH on asthma therapy has found that tailoring treatment to adolescent patients according to their genetic make-up can improve the control of the disease.

Results from the Paediatric Astha Controller Trial (PACT) has shown that genetically guided therapy leads to “a significant improvement in asthma control and quality of life.”

Genetically susceptible patients were given an anti-asthma tablet called montelukast rather than the commonly used drug salmeterol in conjunction with an inhaled steroid.

A picture of a scientific microscope - Research News Scotland
(Photo by Ousa Chea on Unsplash) Asthma affects more than one million children in the UK and, for those suffering with severe asthma, traditional treatments are not always effective

Montelukast was more effective in reducing severe asthma symptoms in 241 participants aged 12-18 compared with the salmeterol-steroid combination, which is currently recommended by asthma treatment guidelines.

The research concludes that genotype-driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care in susceptible adolescent patients.

The patients with the AA homozygous genotype, 15% of all participants, benefited the most.

Professor Brian Lipworth, Head of the Scottish Centre for Respiratory Research at Dundee, said, “We previously reported observational data showing that in about 15% of these genetically susceptible individuals they have more flare ups of their asthma when taking salmeterol as an additional therapy to an inhaled steroid.

“We wanted to see if implementing a genetically tailored intervention whereby susceptible individuals would receive an alternative anti-asthma drug called montelukast instead of salmeterol might improve control when used in addition to inhaled steroid, as compared to a control group where prescribing was done only according to current guidelines.”

 “Few trials have specifically targeted improving control in adolescent asthma patients.

“This is first ever randomised controlled trial in younger people looking at tailoring therapy according to the patients’ genetic make-up, making this a potential game changer for young patients with asthma to improve outcomes.

“Moving forward, our aim is to replicate this study in children with severe asthma who are much younger, such as those from four years and upwards with more severe asthma, who have the same genetic susceptibility.

“This will involve carrying out a head-to-head comparison for the first time with salmeterol versus other long acting drugs which also open up the airways.

“Looking at a different mechanism would allow us to explore all the potential benefits to such genetically guided therapies.

“We need to understand the barriers to implementing this new way of managing children with asthma within the NHS and other healthcare systems worldwide, so that eventually every child in the world can benefit from precision medicine.”

PACT is the first randomised controlled trial of its kind addressing asthma prescribing according to Arg16Gly beta-2 genotype in adolescents. 

Genotypes are the collection of genes responsible for the expression of various genetic traits.

Having this specific genotype means that the adrenergic receptors, which are key in asthma regulation, are less likely to respond to current asthma treatments.

Professor Somnath Mukhopadhyay, Chair in Paediatrics at the Brighton and Sussex Medical School and Chief Investigator for the trial, said, “I hope that the results of this trial will have globally significant implications on the treatment of asthma in young people with this particular genetic susceptibility to poor medicine response in severe asthma.”

The trial was funded by children’s charity Action Medical Research and The Henry Smith charity.

The study also had contributions from the University of Surrey, University of Aberdeen, Nanyang Technological University Singapore, the University of London and the University of Queensland.