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. A post-hoc subgroup analysis found symptom improvement among patients with coeliac 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.
tTG inhibitors may prevent the deamidation and resultant potentiation of gliadin peptides.
Blockers of the interaction of gliadin peptides with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8
These agents may prevent T-cell activation.
Immunomodulation may restore gluten tolerance. For instance, a vaccine may induce immune tolerance to some of the gluten immunogenic peptides, according to phase 1 studies. 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 recruiting.
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.
Early evidence suggests that some strains of probiotics may act on gluten immunogenicity, assist with intestinal healing, and improve patients' symptoms. Caution must be taken because some probiotics may be a source of hidden 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. 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 intra-epithelial lymphocytes, and possibly accelerate mucosal healing.
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