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    2-Drug Strategy May Improve Asthma

    New Approach Targets Production of Mucus
    By
    WebMD Health News

    Feb. 2, 2006 -- A treatment that targets mucus production may one day help asthma sufferers and people with other respiratory diseases breathe much easier.

    Researchers from the Washington University School of Medicine in St. Louis are reporting that a combination of two novel therapies could hold the key to controlling the potentially dangerous buildup of mucus in people with asthma, chronic bronchitis, and even cystic fibrosis.

    Current asthma treatments target inflammation and airway constriction. The two-drug treatment strategy would be the first to target the cellular transformation within the lungs that causes the overproduction of mucus. Mucus plugs block airways, making it difficult for air to go in and out of the lung.

    The findings were reported Wednesday in The Journal of Clinical Investigation.

    "We haven't had good drugs to treat the problem of mucus that are selective, safe, and effective," researcher Michael J. Holtzman, MD, tells WebMD. "In large part, people with asthma and many other respiratory diseases get in trouble because of these secretions."

    Holtzman and Washington University colleagues developed the treatment based on studies in mice and human cell lines. The two-drug combination has not been tested in humans with asthma, but Holtzman says such trials could begin within a year or two.

    "Our research should help in the design of these trials," he says.

    Combining Therapies

    The strategy involves the combination of a new therapy being used to treat late-stage cancers and an experimental therapy being studied for respiratory disease.

    Epidermal growth factor receptor (EGFR) is involved in cell growth. An inhibitor of EGFR has been developed to stop cells from growing and spreading elsewhere in the body. This EGFR inhibitor has been used to treat cancer in humans and has been shown to be relatively safe in clinical trials.

    In this study, mice with a chronic lung condition were exposed to a virus. An inhibitor of EGFR was able to prevent the buildup of mucus-producing lung cells.

    A second inhibitor that targets the interleukin-13 (IL-13) protein is being studied but has not been approved for clinical use. IL-13 is involved in the immune system. The IL-13 inhibitor was shown to block the transformation of cells into mucus-producing lung cells.

    The thinking is that the drugs that inhibit the EGFR and IL-13 proteins may act together to prevent cellular changes that lead to dangerous mucus production in respiratory disease.

    "We have shown that if you combine the EGFR and IL-13 inhibitors in a rational way, you can restore the normal architecture of the airway lining," Holtzman says.

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