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Gluten Degrading Enzymes for Treatment of Celiac Disease

Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, 700 Albany Street, Boston, MA 02118, USA
Institute for Translational Immunology and Research Center for Immunotherapy (FZI), Johannes Gutenberg University (JGU) Medical Center, 55131 Mainz, Germany
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Author to whom correspondence should be addressed.
Current Affiliation: Department of Physical Therapy & Athletic Training, Boston University/College of Health & Rehabilitation Sciences: Sargent College, 635 Commonwealth Ave, Boston, MA 02215, USA.
Nutrients 2020, 12(7), 2095;
Received: 24 June 2020 / Revised: 10 July 2020 / Accepted: 10 July 2020 / Published: 15 July 2020
(This article belongs to the Special Issue Grain Intake and Human Health)
Celiac disease (CeD) affects about 1% of most world populations. It presents a wide spectrum of clinical manifestations, ranging from minor symptoms to mild or severe malabsorption, and it may be associated with a wide variety of autoimmune diseases. CeD is triggered and maintained by the ingestion of gluten proteins from wheat and related grains. Gluten peptides that resist gastrointestinal digestion are antigenically presented to gluten specific T cells in the intestinal mucosa via HLA-DQ2 or HLA-DQ8, the necessary genetic predisposition for CeD. To date, there is no effective or approved treatment for CeD other than a strict adherence to a gluten-free diet, which is difficult to maintain in professional or social environments. Moreover, many patients with CeD have active disease despite diet adherence due to a high sensitivity to traces of gluten. Therefore, safe pharmacological treatments that complement the gluten-free diet are urgently needed. Oral enzyme therapy, employing gluten-degrading enzymes, is a promising therapeutic approach. A prerequisite is that such enzymes are active under gastro-duodenal conditions, quickly neutralize the T cell activating gluten peptides and are safe for human consumption. Several enzymes including prolyl endopeptidases, cysteine proteases and subtilisins can cleave the human digestion-resistant gluten peptides in vitro and in vivo. Examples are several prolyl endopeptidases from bacterial sources, subtilisins from Rothia bacteria that are natural oral colonizers and synthetic enzymes with optimized gluten-degrading activities. Without exception, these enzymes must cleave the otherwise unusual glutamine and proline-rich domains characteristic of antigenic gluten peptides. Moreover, they should be stable and active in both the acidic environment of the stomach and under near neutral pH in the duodenum. This review focuses on those enzymes that have been characterized and evaluated for the treatment of CeD, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. Novel developments include strategies like enteric coating and genetic modification to increase enzyme stability in the digestive tract. View Full-Text
Keywords: celiac disease; gluten; enzyme therapy; treatment; autoimmunity; endopeptidase; glutenase; wheat; enteric coating celiac disease; gluten; enzyme therapy; treatment; autoimmunity; endopeptidase; glutenase; wheat; enteric coating
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MDPI and ACS Style

Wei, G.; Helmerhorst, E.J.; Darwish, G.; Blumenkranz, G.; Schuppan, D. Gluten Degrading Enzymes for Treatment of Celiac Disease. Nutrients 2020, 12, 2095.

AMA Style

Wei G, Helmerhorst EJ, Darwish G, Blumenkranz G, Schuppan D. Gluten Degrading Enzymes for Treatment of Celiac Disease. Nutrients. 2020; 12(7):2095.

Chicago/Turabian Style

Wei, Guoxian, Eva J. Helmerhorst, Ghassan Darwish, Gabriel Blumenkranz, and Detlef Schuppan. 2020. "Gluten Degrading Enzymes for Treatment of Celiac Disease" Nutrients 12, no. 7: 2095.

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