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 found symptom improvement among patients with celiac disease with positive tissue transglutaminase (tTG) despite a gluten-free diet.  
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. 
These agents may prevent T-cell activation.
Immune modulation 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 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 recruiting. 
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. 
Early evidence suggests 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.
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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