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What is Celiac Disease          Current Treatment            Our Approach

• What is Celiac Disease?

Description

Celiac disease is a form of autoimmune disorder that occurs inside the small intestines of about one out of every 133 Americans. Affected individuals cannot properly digest gliadin (a component of gluten), leading to immune responses that may include pain and/or vomiting.

The small intestines are lined with numerous protrusions called "microvilli", which constitute the brush border membrane. In normal small intestines, small peptides and molecules like water diffuse through the brush border membrane and into the bloodstream. Larger molecules such as gliadin are also allowed to diffuse through, but only after they have been converted through a transcellular route.

What happens in celiac disease small intestines?

The brush border membrane in the small intestines of people suffering from celiac disease allows large molecules such as gliadin to go directly into the blood stream without routing them through the transcellular path. Once gliadin passes through, antigen-presenting cells recognize gliadin as a foreign object and attack. This immune response causes pain and other adverse side-effects.

Over time, these side-effects may also damage intestinal villi, which are important for absorbing nutrients. Lack of nutrients can lead to other illnesses such as autoimmune thyroid disease, autoimmune liver disease, and rheumatoid arthritis (diseases in which body immune system attacks healthy cells/tissues) (14).

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• Current Treatments:

Currently, there is no cure for this genetic condition. Prevention of the symptoms associated with celiac disease is accomplished through adopting a gluten-free diet (14, 12, 11). However, gluten is present in most everyday diets, making it difficult to have a gluten-free diet.

"Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach."(8) However, enzymes studied earlier were not able to degrade gluten inside stomach before it reaches small intestine because they were "irreversibly inactivated by pepsin and acidic pH, both present in the stomach."(8)

Over the past years, researchers discovered an enzyme from the bacterium Aspergillus niger. This recently identified prolyl endoprotease was observed to "work optimally at 4-5 pH and [remain] stable at 2 pH".(8) It is possible that this enzyme may provide an alternative treatment for celiac disease. (8) Studies have shown that prolyl endoprotease is able to "degrade gluten in vitro and under conditions similar to the ones present in the gastrointestinal tract." (8) However, due to licensing restrictions we have opted not to work with this protein.

In 2007, a study suggested an alternative approach by combining a glutamine-specific endoprotease (EP-B2 from barley) and a prolyl endopeptidase (SC PEP from Sphingomonas capsulata); with gastric activity and complementary substrate specificity there is a possibility of increasing the safe threshold of ingested gluten (12). An advantage of this “combination product is that both enzymes are active and stable in stomach and can therefore be administered as lyophilized powders or simple capsules or tablets” (12).

Note: This study was first “evaluated via in vitro digestion of whole-wheat bread and then confirmed by in vivo studies in rats (12), unlike other earlier studies which were performed on synthetic gluten oligopeptides, recombinant gliadin proteins, or uncooked gluten” (12).

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