Gene test for asthmatic kids helps target treatment

Mon Jan 7, 2013 7:01pm EST

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By Kate Kelland

LONDON, Jan 8 (Reuters) - Testing children with asthma for a specific gene could help doctors avoid giving them common inhaler medicines that are unlikely to help and may make their condition worse, scientists said on Tuesday.

British researchers studying why certain asthma drugs taken by millions of children don't appear to benefit some patients said a gene called arginine-16 (Arg16) is key to determining which medicines work for some and not for others.

Having a particular change in this gene means a drug called salmeterol, a generic drug used in GlaxoSmithKline's (GSK) Advair, Serevent and Seretide treatments, is unlikely to improve the condition and may exacerbate it, the scientists said.

"We have for the first time shown that personalised medicine can work in the field of children's asthma," said Somnath Mukhopadhyay of Brighton and Sussex Medical School, who led the work and presented his findings at a briefing in London.

Asthma affects more than 300 million people globally and is the world's most common children's chronic illness. Symptoms include wheezing, shortness of breath, coughing and chest tightness. Many children are prescribed salmeterol, a long-acting so-called beta-receptor stimulant, to ease symptoms.

But after finding in a large observational study published in 2009 that some children fail to respond to salmeterol, and linking that to the Arg16 gene, Mukhopadhyay's team decided to look closer. They conducted a genotyped study comparing salmeterol with another generic drug called montelukast.

The researchers took 62 children with asthma who had the susceptible Arg16 genotype and who were still having problems despite using regular steroid preventer inhaler medicines.

The children were then randomly assigned to get either salmeterol or montelukast along with their inhaler, and researchers tracked their progress for a year.

"For almost every symptom we looked at there was a significant difference, and it was always not in favour of salmeterol," Mukhopadhyay said. "These are striking findings."

A spokesman for GSK said that Serevent, which was first licensed in 1990, has since "become one of the most extensively studied asthma medicines" with "a wealth of evidence to support its effectiveness when used appropriately".

"The results of this small study raise interesting questions around how different patients can gain the most benefit from their medicines and it warrants further research," he said.

More than a million children in Britain have asthma and some 150,000 of them have the Arg16 gene change that makes them less likely to respond to salmeterol.

The researchers, whose study was published in the journal Clinical Science on Tuesday, warned that many children around the world with serious asthma who are taking salmeterol but not benefiting from it may be suffering needlessly.

A genetic test which Mukhopadhyay said would cost around 15 pounds ($24) could reveal why, and point doctors to the most effective treatments.

Experts commenting on the findings said they were intriguing and important.

"This is a wonderful example of...personalised medicine working its way into practice," said Stephen Holgate of Southampton University. He said that while the genetic test is not yet available to family doctors, it should be if larger trials find the same results.

Malayka Rahman of the charity Asthma UK agreed further trials are needed to establish whether large-scale Arg16 genetic screening in asthma patients should be introduced.

She also called for more research into genes that affect responses to asthma treatments: "This... area of research has the potential to lead to the tailoring of better treatments for an individual based on their own genetic make-up - ultimately keeping more people out of hospital and preventing unnecessary asthma deaths," she said.

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