1028 New Therapy May Mean Less Dietary Restrictions for Celiac Disease Sufferers - Celiac.com
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New Therapy May Mean Less Dietary Restrictions for Celiac Disease Sufferers

Celiac.com 07/01/2006 - 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. Khoslas group used recombinant bacteria to produce a form of EP-B2 that only activates under acidic conditions similar to the conditions found in the human stomach. The researchers demonstrated that EP-B2 efficiently digested gluten protein under gastric conditions and, importantly, EP-B2 was most specific for those parts of gluten that are known to trigger celiac pathogenesis. In a second study, the researchers went on to devise an even more potent double enzyme therapy for detoxifying gluten.

EP-B2 was tested in combination with another well-characterized enzyme called PEP that breaks gluten protein after proline residues. Like glutamine, proline is also abundant in inflammatory gluten peptides. At very high gluten loads, where neither PEP nor EP-B2 alone could detoxify gluten quickly enough to prevent inflammation, a PEP and EP-B2 combination completely abolished gluten immunotoxicity within ten minutes under simulated gastric and duodenal conditions.

In this tag-team therapy, EP-B2 first cleaved gluten into small pieces under gastric conditions that were then easier for PEP to fully detoxify under duodenal conditions. "Our results suggest that recombinant EP-B2 should be effective as supportive therapy to help celiacs cope with the hidden gluten in everyday life, and that a two-enzyme cocktail containing PEP and EP-B2 may even allow celiacs to resume a more normal diet in the future," offers Dr. Khosla.

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Seigel et al.

The researchers include Matthew Siegel, Michael T. Bethune, Jiang Xia, Alexandre Johannsen, Tor B. Stuge, and Peter P. Lee of Stanford University in Stanford, CA; Jonathan Gass, Jennifer Ehren, Gary M. Gray, and Chaitan Khosla of Stanford University in Stanford, CA and Celiac Sprue Research Foundation in Palo Alto, CA. This research was supported by a grant from the National Institutes of Health (R01 DK63158 to C.K. and Mary Hewitt Loveless, MD Pilot-Project Grant to P.P.L.).

Siegel et al.: "Rational Design of Combination Enzyme Therapy for Celiac Sprue." Publishing in Chemistry & Biology 13, 649–658, June 2006 DOI 10.1016/j.chembiol.2006.04.009 www.chembiol.com

Bethune et al.

The researchers include Michael T. Bethune, Yinyan Tang, and Chaitan Khosla of Stanford University in Stanford, CA; Pavel Strop of Howard Hughes Medical Institute and Stanford University in Stanford, CA; Ludvig M. Sollid of University of Oslo and Rikshospitalet University Hospital in Oslo, Norway. This research was supported by R01 DK063158 to C.K. M.T.B. is a recipient of a National Institutes of Health Cellular and Molecular Biology Training Grant through Stanford University.

Bethune et al.: "Heterologous Expression, Purification, Refolding, and Structural-Functional Characterization of EP-B2, a Self-Activating Barley Cysteine Endoprotease." Publishing in Chemistry & Biology 13, 637–647, June 2006 DOI 10.1016/j.chembiol.2006.04.008 www.chembiol.com.

Contact: Heidi Hardman
Tel: (617) 397-2879

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2 Responses:

 
J Rose
Rating: ratingfullratingfullratingfullratingfullratingempty Unrated
said this on
15 Nov 2007 9:03:31 PM PDT
Great -- I hope soon.

 
Christine
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
22 Jul 2009 9:44:45 AM PDT
Please, Bring it on, we will try anything just to eat again.... The article of research was in 2006 it is 2009 What happen?




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Thank you for posting this I've never been to South America, it's the only continent, bar the poles, I've yet to visit. It's really nice to read that my gluten sensitivity hasn't ruled it out. Maybe I'll get to the land of Luis Suarez yet!

I know this post is a year ago... however it is still on the first page of the travel section! I am from Uruguay, (South America) and I can answer this question for people that may look at it in the future. As a South American - I can say that the cuisine varies greatly. In cities, you shouldn't have any more than the normal amount of difficulty finding food. For example, in Montevideo, the city I am from, you'll have no problem finding dedicated entire Celiac stores. Meat is a large part of restaurant menus, so parilladas (similar in theory to steakhouses, would be very easy to navigate). Uruguayans do eat a lot of pastries, and just like in the states... Most mainstream bakeries are not gluten free, but like I mentioned there are places that specialize. In Uruguay, there is knowledge of Celiac and a large health awareness. Some of the foods can be costly, cost of living in general is not low. In large swaths of South America, the foods you mentioned - Potatoes, rice, meat, etc are abundant, as are fresh fruits and veggies. Avoiding corn does make it tricky. Peru can be a great place for non-gluten eaters. Peru uses very little gluten (they are the original quinoa eaters) but there is a lot of corn in the diet (and since you are corn sensitive, that would be a food you would need to navigate). Latin America spread over two continents! In this area you will find a great variety in cultures, cuisines, and knowledge of celiac. There is no reason why If you want to experience Latin America, that you have to rule out an entire region of the world because of Celiac. Navigating it will be different, but it is doable!

Recently diagnosed last week does the pain ever get better??

George, i am sorry that you are not feeling well! ?? I am not a doctor, but just trying out drugs to stop your symptoms just seems like a band aid approach. It sounds like he suspects IBS which is really, in my opinion, "I be stumped". Has inflammatory bowel disorder (IBD) (more lovely autoimmune disorders) been ruled out? This includes both Crohn's and Colitis. My niece was diagnosed with Crohn's finally with a pill camera after all other tests were given. The damage was not within reach of any scope. I am just throwing out suggestions. Hopefully, you and your doctor will figure it out soon!

Celiac disease is an autoimmune disease that happens to have a known trigger -- gluten. Flare-ups develop (antibodies) causing damage. Not just in the small intestine, but systemically. One gluten exposure can cause antibodies to increase for days or months! Antibodies are being measured during the celiac blood tests. If there is no gluten exposure, there will be no antibodies. These antibodies can come down in some people in as little as two weeks. Recommendations require gluten 2 to 4 weeks daily for the biopsies taken via endoscopy in order to be sure to catch damage, but 8 to 12 weeks for the blood tests. The endoscopy is considered the "gold standard" in helping to diagnose celiac disease, but there are other things that can damage the small intestine. So, the blood test helps solidify the diagnosis. So, if you want a good result on your endoscopy, you need to be eating gluten daily for two week prior at a minimum. I know it is tough and you are feeling sick. Wish there was a better way to catch active celiac disease.