A New Oral Therapeutic for Celiac Patients?

ImageCeliac disease is an autoimmune condition that manifests a wide range of symptoms in response to gluten consumption in affected individuals. Although the disease can cause autoimmune responses in many organs, the main damage occurs in the small intestine via the body’s immune cells attacking normal human tissues[i].

The current treatment for celiac disease is strict adherence to a gluten-free diet, which includes elimination of wheat, barley and rye. However, a recent scientific breakthrough may allow celiac patients to consume these products without suffering autoimmune issues. 

α-gliadin is a protein in wheat, which is thought to cause the inflammatory reaction associated with Celiac disease. During digestion, α-gliadin is broken down into smaller fragments, termed peptides, which are unable to be further degraded due to their unusual chemical properties. These peptides are thought to produce the autoimmune response seen in celiac patients.

Researchers at UC Davis have used a computational approach to engineer an enzyme capable of breaking down the problematic α-gliadin peptides. The researchers sought an enzyme that could: 1) work under the acidic conditions in the stomach, 2) resist degradation by other digestive enzymes, 3) work optimally at human body temperature, 4) selectively degrade the unusual α-gliadin peptides.

To design the enzyme, researchers first isolated a candidate enzyme from the bacteria Alicyclobacillus sendaiensis. Then, they used computer models to optimize the enzyme’s ability to specifically degrade the α-gliadin peptides. After mutating certain parts of the enzyme to optimize its performance, the enzyme was able to degrade over 95% of the α-gliadin peptides in physiologically relevant conditions.

This enzyme still must be tested in animal models and eventually in humans. Also, it is not certain that degrading these specific α-gliadin peptides will eliminate the autoimmune response in celiac patients, as there could be other peptides responsible for causing the autoimmune response. Whether humans should be eating wheat, putting aside autoimmune issues, is another question as there are concerns about wheat’s propensity to spike blood sugar and potential for addiction due to it’s opioid content. Nonetheless, this breakthrough represents an important development in treating Celiac disease.

Find the original study at: http://pubs.acs.org/doi/abs/10.1021/ja3094795

[i] Rostom A, Murray JA, Kahnoff MF. (2006) American Gastroenterological Association Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 131: 1981-2002.

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