Non-dietary therapies for celiac disease

Abstract The gluten-free diet (GFD) has proven to be an imperfect treatment for celiac disease (CeD) for many subjects. Additional therapeutic options may be useful in combination with the GFD for persistent/recurrent CeD symptoms, for preventing acute symptomatic reactions, and decreasing disease burden by perhaps one day allowing CeD patients to include a certain amount of gluten in their diet. Therapeutic strategies include 1) decreasing intestinal mucosal exposure from gluten's toxic and immunogenic peptides (Glutenases [Latiglutenase and Kuma]), AGY, single chain variable fragment (scFv), polymer P(HEMA-co-SS), and probiotics 2) decreasing intestinal permeability (the Zonulin antagonist Larazotide) and 3) inhibiting the immune proinflammatory response (inhibitors/antagonists of tissue transglutaminase, IL-15, CCR9, γc Receptor, elafin, and cathepsin). Immune tolerizing techniques are a new, promising approach, for which CeD with its very well described antigen may be a perfect model; some of the therapies tested include the vaccine NexVax2, and the nanoparticle-based TIMP-Glia. This chapter further analyzes the advantages and pitfalls of these therapies, and details the broad principles for drug testing, including outcome measures, gluten challenge, use of gluten immunogenic peptide testing, animal testing, and clinical trial designs.