Alternative treatment for secretory diarrhea linked to the cystic fib...( Secretory diarrhea is the leading cause...)

Secretory diarrhea is the leading cause of death in children less than 5 years of age in developing countries, and a frequent and most unwelcome diagnosis for many adults that is made, on average, up to four times each year. Many common causes of diarrhea exist: bacterial or viral infections resulting from consumption of contaminated food or water; food intolerances; reactions to medicines; bowel disorders and intestinal diseases. Diarrhea results when cells lining the intestine secrete an excess of chloride, via a chloride channel within the cell, as well as sodium in reaction to one of these causal agents. The high level of resulting salt in the intestine causes water removed from the blood to be directed to the gut, thereby producing fluid diarrhea. The most serious and life-threatening development during a bout of diarrhea is dehydration due to continued removal of water from the circulation.

In 1989 the cystic fibrosis gene was identified and found to encode a chloride channel in cells lining the lung. Recognized as the cystic fibrosis transmembrane conductance regulator (CFTR), no compounds were known to inhibit the activity of this channel - until now.

In the December 2 issue of the Journal of Clinical Investigation, Alan Verkman and colleagues at the Cardiovascular Research Institute at the University of California, San Francisco, developed a high-throughput screening assay to identify compounds that inhibit the activity of CFTR. The authors identified an organic compound, thiazolidinone, effective in inhibiting CFTR-mediated chloride secretion. To test the therapeutic value of thiazolidinone the authors investigated it's utility in mice suffering secretory diarrhea. The authors reported a successful reduction of excess intestinal fluid secretion via inhibition of the chloride channel within cells lining the gut.

Will this drug, or its derivatives, be useful in the treatment of secretory diarrhea? In his accompanying commentary Dr.
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Contact: Brooke Grindlinger
212-342-9006
Journal of Clinical Investigation
3-Dec-2002

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