Novel therapeutic approaches for celiac disease.

Celiac disease, which mainly affects the small intestine, is the only systemic autoimmune disorder with an identified environmental trigger which is dietary gluten. Lifelong adherence to a strict gluten free diet (GFD) is currently the only accepted treatment. Celiac disease is increasingly diagnosed and the GFD is known to be associated with a large treatment burden. Furthermore, a substantial number of celiac disease patients show an incomplete clinical response to the GFD. These factors have led to demands for the development and testing of novel, non-dietary, therapeutic agents that are both safe and effective. Celiac disease pathogenesis is well elucidated which has greatly aided targeted drug development. Compounds currently being tested in phase II clinical trials include glutenase enzymes (to detoxify gluten) and a tight junction modulator (to reduce access of gluten peptides to lamina propria antigen presenting cells). Other promising approaches include inhibition of the transglutaminase 2 enzyme, blocking antigen presentation by HLA-DQ2 or HLA-DQ8, induction of tolerance, and modulation of the inflammatory response. It is hoped that non-dietary therapy for celiac disease will become available in the coming years and can both reduce the burden of treatment of celiac disease and help patients whose symptoms do not respond completely to the GFD.