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Alternatives to the Gluten Free Diet: Are We There Yet? By Michelle Pietzak, MD

This article appeared in the Spring 2007 edition of Celiac.coms Scott-Free Newsletter.

Celiac.com 08/29/2007 - The XII International Celiac Disease Symposium, proudly hosted by the Celiac Disease Center at Columbia University, featured presentations from researchers from all over the globe. The last session of the scientific portion of the symposium, entitled “Non-Dietary Therapies”, was full of controversy and fireworks. Talks given by Drs. Khosla, Gray, Paterson, Anderson and Mitea all revealed that potential alternatives to the gluten free diet are now being aggressively pursued. Several groups have even spun off from pharmaceutical companies to raise funds to test these alternatives in patient trials. However, several questions remain. How close are we to a “pill” or “vaccine” to treat or prevent celiac disease? And do we even need, or more importantly, WANT them, given that the diet is safe and effective?

Any alternative therapy for celiac disease must be at least as safe as the gluten-free diet, which, if done correctly, has NO side-effects. So the bar is raised very high. An alternative must offer great medical benefit to celiac patients without causing any medical harm. It is also unclear how, exactly, these new therapies will be implemented. Can they treat existing celiac disease? Will they prevent those at increased risk for the disease (such as siblings) from having symptoms? Will these medications allow celiac patients to ingest as much gluten as they want, or will they just take away the fear of contamination when eating questionable foods? What follows is a summary of several important points raised by some of these speakers in regard to the research that their center is doing in this area of “alternative therapies for celiac disease.

Two groups discussed their research on what has commonly become known as “the celiac pill”. The idea behind the “pill” is somewhat similar to the idea of taking a lactase enzyme supplement to digest the milk sugar lactose (if you are lactose intolerant). However, digesting the proteins that trigger the immune reaction in celiac disease is much more complex than digesting the simple sugar found in dairy products. The small fragments of the gluten proteins from wheat, rye and barley, which stimulate the immune system in someone with celiac disease, contain a large quantity of an amino acid called proline. The stomach and pancreatic enzymes in humans have difficulty digesting the fractions where these prolines are located, making the gluten highly resistant to complete digestion. The idea behind the “celiac pill” is to provide enzymes to break down the gluten into smaller fragments which will not be recognized by a celiac patient’s immune system. Therefore, theoretically, gluten would not cause an immune reaction and could be safely eaten.

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Dr. Gary Gray, an adult gastroenterologist working at Stanford University in California, addressed this issue in his presentation “Oral Enzyme Therapy”. Their study looked at 20 biopsy-proven celiacs in remission (without symptoms) who received orange juice with either gluten or gluten pre-treated with a special enzyme (abbreviated PEP, for prolyl endopeptidase). Each patient consumed a low dose of gluten daily, 5 grams, which is equivalent to one slice of bread. The patients completed a daily symptom questionnaire, and had urine and stool tests of to measure intestinal damage. The researchers concluded that pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who, after a 2-week gluten challenge, developed fat or carbohydrate malabsorption. The PEP enzyme needs to be investigated further in larger trials of celiac patients.

Cristina Mitea, working with Dr. Fritz Koning at Leiden University in The Netherlands, also presented some data using similar technology, entitled “Enzymatic degradation of gluten in a GI-tract model”. This group published in 2006 that the above described PEP enzyme may not work optimally in the celiac patient, since it is not active at low stomach pH. The PEP enzyme may also be broken down by pepsin, a digestive enzyme in the stomach, before it reaches the small bowel where gluten causes the most damage. Given these facts, this group of researchers characterized a prolyl endoprotease enzyme, derived from the fungus Aspergillus niger, abbreviated AN-PEP. The AN-PEP enzyme, according to some publications, has been shown to work at stomach pH while resisting pepsin digestion. In the lab, the AN-PEP was able to degrade intact gluten as well as small fragments of gluten, including those that stimulate the immune system in patients with celiac disease. It also appeared to act within minutes, which is 60 times faster than PEP. This is particularly important, as ingested gluten will leave the stomach to enter the small bowel within 1 to 4 hours after being eaten. These researchers state that this enzyme is very stable, and could be produced at low cost at food-grade quality in an industrial setting. However, it has not yet been tested in human clinical studies.

In summary, some of these future potential treatments include:

  • The development of genetically detoxified grains
  • Oral or intranasal celiac vaccines to induce tolerance
  • Inhibitors to the effects of zonulin on intestinal permeability
  • Detoxification of immunogenic gliadin peptides (or gluten proteolysis) via oral peptidase supplementation
  • Inhibitors of tissue transglutaminase

Dr. Michelle Pietzak, “The Gluten Free MD” is an Assistant Professor of Clinical Pediatrics at the University of Southern California Keck School of Medicine. She sees patients at Childrens Hospital Los Angeles and Los Angeles County Women’s and Children’s Hospital. With New Era Productions, she has recently released an audio celiac disease set as well as a 2 disc DVD set about celiac disease and the gluten free diet, available at www.glutenfreemd.com.

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4 Responses:

 
Ajai Nair
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said this on
30 Dec 2007 9:56:11 AM PDT
Has there been any progress toward a clinical trial of AN-PEP. I read a ton about it in 2007, but nothing about testing.

 
Thomas Larson
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said this on
22 Feb 2008 5:08:27 AM PDT
An interesting article.

I was diagnosed with Celiac Disease about 3 months ago. Since then I have read everything I could find on the disease on-line.

Recently I received a mailing from someone who was not identified for a product named 'Gluten Digest.'

I can find no 'reviews' for this product on-line. It supposedly helps a celiac digest gluten without a negative reaction.

 
Frank
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said this on
29 Jan 2009 12:10:27 PM PDT
There are several companies the tout a product for gluten sensitivities and you need to be cautious as they mostly all use DPPIV which is used in the majority of cases for Lactose intolerance. There have not been any clinical studies on the ANPEP yet and as far as I know it is not commercially available.

 
michael jones
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said this on
28 Jan 2011 2:53:38 AM PDT
My son has just been told he has celiac disease just trying to find out about it




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Hi Dalek, JMG has it right, any food with wheat, rye or barley is a gluten containing food. In addition, watch out for malt, which is sometimes made from barley. That includes the malt in beers.

Interesting!! I'm going to share that with her dr. I'll have to look into the gluten sensitivity more myself, the main reason we started testing is due to poor growth. As I learned more, I've seen several symptoms that could be explained by celiac. I like feeling informed so I'll know what to talk to the dr about or ask about. I think those are the results we are waiting for still, I couldn't remember the name.

Call your doctor's office and ask them to relay your request to the doctor to amend the test request, they should be able to sort it without an additional meeting and delay. Worth a try anyway I think the Biocard tests TTG IGA and it may give you an indication. Do post your results here as I'm sure others will be interested in its effectiveness. If it's negative however remember that there are several celiac tests for a reason. Some test on one, some on another etc... However my guess is your doctor will dismiss them and want their own testing. That's the usual experience.

Waiting for the EMA, I bet. Keep advocating! this is interesting. If celiac disease is excluded, she might still have a gluten sensitivity. There just is not specific test for that. http://theglutensummittranscripts.s3.amazonaws.com/Dr_Umberto_Volta.pdf

I think all the flavors are all gluten free. I buy them at my local grocery store which is a Kroger store. Amazon has them too. Jenny at "The Patient Celiac" uses them too (she is a preemie doctor who has celiac disease).