Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease

• DOI: 10.1038/srep30980
• Publication Date: 2016-08-02T09:11:48Z
• Authors: Martial Rey; Menglin Yang; Linda Lee; Ye Zhang; Joey G. Sheff; Christoph W. Sensen; Hynek Mrazek; Petr Halada; Petr Man; Justin L McCarville; Elena F. Verdu; David C. Schriemer
• Keywords: Proteolytic enzymes; Degradation

Abstract Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness high. Current options require enzyme amounts on same order as meal itself. In this study, we evaluated proteolytic components of carnivorous pitcher plant ( Nepenthes spp.) for use context. Remarkably low doses enhance gliadin solubilization rates and degrade slurries within pH temporal constraints human gastric digestion. Potencies excess 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin neprosin , latter novel defining previously-unknown class prolyl endoprotease. The digests also exhibit reduced TG2 conversion immunogenic regions gliadin, providing twin mechanism evading T-cell recognition. When sensitized dosed with enzyme-treated NOD/DQ8 mice did not show intestinal inflammation, when compared challenged only pepsin-treated gliadin. load needed effective suggests detoxification can be achieved setting, using metered dosing based size. We demonstrate showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1.