Stepniak D et al. (2006) Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol 291: G621–G629

Celiac disease is caused by an immune response to the digestion products of wheat gluten. Gluten is incompletely digested because of its high proline content—human digestive enzymes are unable to cleave proteins at proline residues. In susceptible individuals, some gluten peptides trigger a T-cell response, causing inflammation in the small intestine. Diet supplementation with nonhuman prolyl oligopeptidases, which can cleave proteins at proline residues, has been suggested as therapy for celiac disease, but the enzymes tested do not function at gastric pH, and are efficiently degraded by pepsin. Researchers in the Netherlands have now evaluated a newly discovered prolyl endoprotease from Aspergillus niger (AN-PEP) as a potential treatment for celiac disease.

AN-PEP is active between pH 2 and pH 8, with peak activity at pH 4–5. The enzyme retains its activity after incubation for 60 min at pH 2, and is resistant to pepsin degradation. Intact gluten is degraded effectively by AN-PEP, and gluten peptides are digested 60 times faster by AN-PEP than by a prolyl oligopeptidase. Almost all gluten-derived immunostimulatory peptides are destroyed by AN-PEP, and the T-cell stimulatory properties of a pepsin/trypsin digest of gluten are eliminated or greatly reduced by AN-PEP.

The authors conclude that AN-PEP is active throughout the pH range encountered in the human digestive tract. AN-PEP's pepsin resistance, high catalytic rate, activity against intact gluten and effectiveness against immunostimulatory peptides make it a promising candidate for clinical trials to evaluate oral AN-PEP supplementation in the treatment of celiac disease.