Emerging treatments

Endopeptidases

Latiglutenase (formerly ALV003) may digest gluten within the intestinal lumen resulting in non-antigenic peptides. One study failed to demonstrate overall histological or symptom improvement in non-responsive coeliac disease.[111] A post-hoc subgroup analysis suggested symptom improvement among patients with coeliac disease with positive tissue transglutaminase (tTG) despite a gluten-free diet.[112]

Tight junction regulators

Larazotide may strengthen tight junctions and prevent gluten from infiltrating the mucosa.[113] Symptomatic improvement among individuals experiencing continued symptoms, despite gluten-free diet adherence, has been noted.[102][113]

Tissue transglutaminase (tTG) inhibitors

tTG inhibitors may prevent the deamidation and resultant potentiation of gliadin peptides.[20] One phase 2a efficacy/tolerability study of the tTG inhibitor ZED1227 is ongoing (in patients with well-controlled coeliac disease undergoing gluten challenge).[114]

Immunomodulation

Immunomodulation may restore gluten tolerance.[115] TIMP-GLIA is a nanoparticle-based therapeutic being studied for the treatment of coeliac 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.[116]

Interleukin-15 antagonists

Interleukin-15 has been shown to be a key component for intra-epithelial lymphocyte survival and mucosal damage. Agents that act to block this cytokine are under development for non-responsive and refractory coeliac disease. One phase 2a trial of an interleukin-15 inhibitor, AMG 714, in patients with refractory coeliac disease reported no change in the proportion of aberrant intra-epithelial lymphocytes in the treatment group compared with the placebo group. The patients in the treatment group reported a reduction in diarrhoea symptoms.[117]

Probiotics

Early evidence suggests that some strains of probiotics may act on gluten immunogenicity, assist with intestinal healing, and improve patients' symptoms.[118][119] 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, hydrolysation with lactobacilli and fungal proteases, or gene sequencing alterations.[120][121][122] Treatment of wheat flour with microbial transglutaminases is another option being explored.[123]

Montelukast

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 intra-epithelial lymphocytes, and possibly accelerate mucosal healing.[124]

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