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New therapy may mean less dietary restrictions for celiac sufferers

Scientists have discovered what may be a successful non-dietary therapy for celiac sprue, an inherited inflammatory disorder of the small intestine that impacts an estimated 1 in 200 people around the world. Two research studies, published in the June issue of Chemistry and Biology, pave the way for clinical testing with an oral enzyme therapy that may prevent the many symptoms and complications of this widespread disease.

People with celiac sprue, also called celiac disease, cannot tolerate the protein gluten in their diet. Gluten is present in grains like wheat, barley, and rye. When gluten is ingested by a celiac patient, it sets off an inflammatory reaction that damages the small intestine, leading to malabsorption, an autoimmune-like response, and many other complications. The only effective therapy for celiac disease is complete dietary exclusion of gluten. However, the ubiquitous nature of gluten poses a constant threat to celiacs, and a majority of celiac patients who adopt a restrictive diet still exhibit structural and functional gut abnormalities.

"Non-dietary therapies that allow celiac patients to safely incorporate low-to-moderate levels of gluten into their daily diet would be of considerable benefit," explains study leader Dr. Chaitan Khosla, from Stanford University and Celiac Sprue Research Foundation. "Having demonstrated earlier that certain types of enzymes can detoxify gluten, our laboratory set out to devise an optimal oral enzyme therapy for celiac sprue by borrowing from nature. In germinating barley seed, gluten serves as a nutritious storage protein that is efficiently digested by enzymes. One enzyme, EP-B2, plays a crucial role in this process by breaking gluten proteins after glutamine residues, which comprise one-third of all amino acid residues in gluten."

Dr. Khosla's group used recombinant bacteria to produce a form of EP-B2 that only activates under acidic conditions similar to the conditions found in the h
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
23-Jun-2006


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