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Researchers find trigger for devastating digestive disease, propose treatment

Researchers have found a peptide molecule that triggers celiac sprue a severe inflammation of the intestine that results from eating wheat and related grains and propose a treatment strategy that relies on bacterial enzymes to break down the offending molecule in the digestive tract. As many as 1 in every 200 Americans suffers from the condition.

In the September 27 issue of Science, Chaitan Khosla and his coworkers at Stanford University and the University of Norway in Oslo, report disassembling the large, complex mixture of gluten proteins and identifying a single component that triggers the autoimmune response characteristic of celiac sprue.

The study presents, "a combined chemical-physiological-immunological answer to the question 'why is gluten toxic to a person with celiac sprue?,'" said Khosla, whose work is supported by the National Science Foundation (NSF). "If proven correct, the findings will lead to new insights into the causes of celiac sprue, and perhaps certain other types of autoimmune diseases."

The researchers determined that the autoimmune response in people with celiac sprue can be traced to an unusually long molecule a chain of 33 amino acids that cannot be broken down by the human digestive system. They immersed the 33-amino acid chain in digestive enzymes derived from bacteria and found that a bacterial enzyme, prolyl endopeptidase, can break the chain into apparently harmless components.

"The technology used to isolate and identify the peptide trigger for celiac sprue, and the enzymology used to neutralize the disease, are marvelous examples of how research into the fundamental understanding of life processes can directly influence human health," said Fred Heineken, program director in NSF's Biochemical Engineering/Biotechnology Program.

Celiac sprue is often diagnosed only after years of painful symptoms. Presently, there is no cure. The only treatment is to completely avoid grains that contain gluten
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Contact: Josh Chamot
jchamot@nsf.gov
703-292-8070
National Science Foundation
26-Sep-2002


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