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Synthetic Antibody Neutralizing Gluten in Development

Oliver Spadiut

Oliver Spadiut (Technical University Vienna)

25 September 2018. An academic-business team is developing a synthetic antibody to prevent gluten found in some grains from affecting the intestines of people with celiac disease, an intolerance of gluten. Researchers from the chemical engineering lab led by Oliver Spadiut at Technical University Vienna in Austria and the company Sciotech Diagnostic Technologies GmbH in Tulln, Austria reported results of their lab tests on the synthetic antibody earlier this year in the journal BMC Biotechnology.

Celiac disease is an inherited immune-system disorder where people cannot tolerate gluten, a protein found in wheat, rye, barley, and some other substances. The immune reaction to gluten causes inflammation in the lining of the small intestine, which prevents absorption of nutrients. Without treatment, inflammation from celiac disease can lead to long-lasting damage in the small intestine, as well as malnutrition, since needed nutrients are not being taken into the body. About 1 percent of the U.S. population has celiac disease, with a similar percentage found in Europe.

While treatments are available for celiac disease, they often involve regulating the immune system, which poses risks for many patients. Spadiut and colleagues are seeking a safer option that blocks the toxic effects of gluten in people with celiac disease. Their strategy is to develop fragments of antibodies that fit precisely into gluten’s chemistry to prevent the protein from activating an immune response in the intestines of people with the disorder. Spadiut’s lab studies production of synthetic antibody fragments in genetically-engineered E. coli bacteria. E. coli is popularly known as a cause of food poisoning, but is also a well-studied and documented benign model species in many labs.

The researchers in this case genetically engineered E. coli to produce antibody fragments with improperly folded proteins, making different amino acids in their complex antibody chemistry appear on the protein’s surface. These misfolded protein parts are called inclusion bodies, also a research focus of the TU Vienna lab. The lab reprogrammed E. coli bacteria, a complex and painstaking process, to produce inclusion bodies that could bind directly with and deactivate prolamins, proteins stored in grains that include gluten. In the journal article, the researchers tested their synthetic antibody fragments in the lab with prolamins from several grains, and found the fragments bound to and blocked prolamins, although with somewhat greater effect in barley than wheat.

The collaboration with Sciotech Diagnostic Technologies aims to scale-up the process and commercialize the engineered antibody fragments into a medical food product. The company develops products for people with food allergies, but Spadiut says in a university statement that the mechanism of the new product still needs to be worked out. “It remains to be seen whether the symptoms will disappear completely or will only be alleviated,” notes Spadiut. “The precise effects will probably vary from person to person. In any case, we firmly expect the product to be available in ordinary pharmacies as early as 2021.”

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