Latiglutenase (formerly ALV003) may digest gluten within the intestinal lumen resulting in nonantigenic peptides. One study failed to demonstrate overall histologic or symptom improvement in nonresponsive celiac disease. A post-hoc subgroup analysis suggested symptom improvement among patients with celiac disease with positive tissue transglutaminase (tTG) despite a gluten-free diet.
Tight junction regulators
Larazotide may strengthen tight junctions and prevent gluten from infiltrating the mucosa. Symptomatic improvement among individuals experiencing continued symptoms, despite gluten-free diet adherence, has been noted.
Tissue transglutaminase (tTG) inhibitors
tTG inhibitors may prevent the deamidation and resultant potentiation of gliadin peptides. One phase 2a efficacy/tolerability study of the tTG inhibitor ZED1227 is ongoing (in patients with well-controlled celiac disease undergoing gluten challenge).
Immune modulation may restore gluten tolerance. TIMP-GLIA is a nanoparticle-based therapeutic being studied for the treatment of celiac disease. It is designed to reverse gluten sensitivity and stimulate immune tolerance by delivering encapsulated gliadin to tolerogenic immune cells. Phase 1 trials are in progress.
Interleukin-15 has been shown to be a key component for intraepithelial lymphocyte survival and mucosal damage. Agents that act to block this cytokine are under development for nonresponsive and refractory celiac disease. One phase 2a trial of an interleukin-15 inhibitor, AMG 714, in patients with refractory celiac disease reported no change in the proportion of aberrant intraepithelial lymphocytes in the treatment group compared with the placebo group. The patients in the treatment group reported a reduction in diarrhea symptoms.
Early evidence suggests some strains of probiotics may act on gluten immunogenicity, assist with intestinal healing, and improve patients' symptoms. Caution is advised because some probiotics may be contaminated with gluten.
Modified wheat gluten
Various methods are being examined to alter the gluten immunogenic peptides present in wheat flour, thus decreasing their immunogenicity, either by microwaves, gamma irradiation, hydrolyzation with lactobacilli and fungal proteases, or gene sequencing alterations. Treatment of wheat flour with microbial transglutaminases is another option being explored.
A pilot study has shown that montelukast, a leukotriene receptor antagonist used for the treatment of asthma, could suppress the production of inflammatory mediators by intraepithelial lymphocytes, and possibly accelerate mucosal healing.
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