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Scientists Discover Molecular Trigger Of Mucus Production, Suggesting First Treatment For Deadly Bronchitis, Other Diseases

Scientists have discovered the deadly trigger that can initiate uncontrolled mucus production, a malady that kills millions of people a year by blocking their airways. Chronic bronchitis, cystic fibrosis and acute asthma, all caused by blocked airways, affect about 20 million people in the U.S. There are no known cures.

The new finding by researchers at the University of California San Francisco points to a straightforward strategy to prevent mucus from accumulating and blocking airways. The researchers found that a well-studied cell messenger signals a mucus-producing gene to turn on, and they suggest that drugs targeting this messenger can keep the gene switched off.

"Hypersecretory diseases like cystic fibrosis and chronic bronchitis take a terrible toll, but no drugs have ever been developed to cure them," said Jay Nadel, M.D., UCSF professor of medicine and physiology. "Now that we know the chemical cascade that activates this mucus gene we should be able to develop strategies to control mucus production and prevent it from blocking airways." Nadel is senior author of a report on the research appearing in the current issue of the Proceedings of the National Academy of Sciences.

Hypersecretory diseases have been untreatable because no one knew what triggered mucus-producing genes, nor how to block this action. In these diseases, epithelial cells develop into mucus-filled "goblet" cells, and when the goblet cells secrete the viscous mucus, it expands many hundred-fold in the water along the airway surface, blocking small air passages.

"Victims literally drown in their own secretions," Nadel explained. In the UCSF research, rats that were induced to turn on mucus genes developed goblet cells. But when the animals were treated with a drug to block a cell messenger known as tyrosine kinase, the mucus genes were turned off. Nadel hopes further animal studies and then clinical trials of this strategy will lead quickly to the first effective treat
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
16-Mar-1999


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