Gene Sleuths Find a Link to Asthma


In the U.S. alone, asthma afflicts some 14 million people, costing the country's health-care system an estimated $14.5 billion annually. While no cure exists, and none is on the horizon, a team of researchers reported on July 10 that by screening 450 families in Britain and the U.S., it has identified a gene linked to asthma.

The finding was reported in the July 11 issue of scientific journal Nature by Dr. Stephen T. Holgate, a medical professor at Britain's University of Southhampton, working with researchers from Genome Therapeutics in Waltham, Mass. Holgate says the gene is particularly significant because, rather than controlling the inflammation of the airways and lungs that's asthma's hallmark, it controls the contractions of muscles lining the airway.

FAMILY GROUPS. Asthma sufferers are known to have particularly "twitchy" muscles, which contract at the slightest stimulus. These contractions, combined with the swelling caused by inflammation, cause victims to gasp for breath. The gene discovery, says Holgate, provides a new target for both drug treatments and diagnosis for the disease.

New targets are certainly needed. All treatments now on the market, from bronchodilators such as salbuterol to inhaled steroids, only provide relief from symptoms.

Although environmental factors such as prolonged exposure to allergens are a recognized risk factor for the disease, researchers have long been aware that the disease runs in families. To locate a genetic cause, Holgate and his team recruited 352 families from the south coast of England and 98 from the U.S. in which two or more children had asthma. An additional 200 so-called hypernormal families, which have no history of asthma for at least two generations, were also recruited as a control group. It took 15 months to assemble the families and five more years to screen their blood samples using Genome Therapeutics' gene-sequencing technology.

"COMBINATION OF MUTATIONS." The asthma gene, dubbed ADAM33, is extremely complicated, says Holgate, with four different functions related to muscle contraction. The researchers also identified some 55 mutations in the gene, with 8 to 10 of these associated with increased susceptibility to asthma. "You would need a combination of these mutations to actually influence the development of asthma," Holgate says. Despite its complexity, he believes the gene is a good target for a drug and could possibly even lead to a cure.

Genome Therapeutics identified the gene in partnership with Schering-Plough, which is now attempting to develop a asthma drug based on the discovery. Holgate estimates that will take at least eight years. However, he says a diagnostic test -- which would identify people highly susceptible to asthma before they develop it, so that they can take preventive measures -- could be available sooner. By Catherine Arnst in New York


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