Combinatorial enzyme therapy to digest gluten in celiacs

August 13, 2007 – By dissecting the unique characteristics of gluten, researchers at Stanford University have discovered an intimate link between the proteolitic stability (resistance to digestion) and the immunological toxicity of gluten; this knowledge has translated into the design of an oral enzyme therapy with promising potential for celiacs and for all people suffering from gluten intolerance.

Gastroenterology. 2007 Aug;133(2):472-80. Epub 2007 May 21

Combinatorial enzyme therapy to digest gluten in celiacs.

Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue.

Gass J , Bethune MT , Siegel M , Spencer A , Khosla C.

Department of Chemical Engineering, Stanford University, Stanford, California.

Background & Goals: Celiac sprue is a multifactorial disease characterized by an inflammatory response of the small intestine to undigested gluten. Resistant to digestion, rich in proline and glutamine, gluten peptides from wheat, rye and barley persist in the intestinal lumen and elicit an immune response in genetically predisposed individuals. We investigated a novel enzyme product combination, i.e., a glutamine-specific endoprotease (EP-B2 from barley) and an endopeptidase propyl (SC PEP from Sphingomonas capsulate), for its ability to digest gluten under gastric conditions.

Methods: The ability of this enzyme combination to digest and detoxify whole wheat bread was studied. Experimental “in vitro” and “in vivo” (rats) systems were developed to simulate human gastric digestion and the resulting material was analyzed by high performance liquid chromatography, enzyme immunoassay (ELISA) and cell proliferation assays. -T in patients.

Results: Analysis reveals that EP-B2 extensively proteolyzes (breaks down) complex bread proteins, while SC PEP rapidly detoxifies residual oligopeptides, products of EP-B2 digestion. The “in vitro” data regarding variation in doses suggests that a weight ratio of the two enzymes of 1:1 should maximize their synergistic potential. The effectiveness of these two enzymes was verified in a rat gastric digestive model.

Conclusions: By combining two enzymes with gastric activity and complementary substrate specificity, it should be possible to increase the safe threshold for gluten ingestion and therefore alleviate the burden of the highly restrictive diet followed by patients with celiac sprue.