Larazotide

Larazotide (AT-1001, Larazotide Acetate) is a synthetic octapeptide designed to regulate intestinal tight junction permeability by antagonizing zonulin, the only known physiological modulator of intestinal tight junctions. Research demonstrates larazotide reduces intestinal permeability ("leaky gut") by preventing tight junction disassembly triggered by gluten and other inflammatory stimuli. Clinical trials have evaluated larazotide for celiac disease, showing reduction in gluten-induced symptoms and intestinal permeability markers in patients inadvertently exposed to gluten. The peptide acts locally in the gastrointestinal tract with minimal systemic absorption. Studies indicate potential applications for other conditions involving intestinal barrier dysfunction including inflammatory bowel disease, type 1 diabetes, and autoimmune disorders linked to increased intestinal permeability. Larazotide represents a novel mechanism-based approach targeting the intestinal barrier as a therapeutic intervention point. Phase 3 clinical trials for celiac disease have been conducted with mixed results, and development continues.

No approved therapy; the phase 3 failure suggests limited clinical efficacy; effects on mucosal healing (vs symptoms) were not established; development was discontinued, so no further trials are planned by the sponsor.

Synthetic octapeptide modeled on the zonula occludens toxin (Zot) that inhibits paracellular permeability by modulating intestinal tight junctions. Administered orally. Clinical pharmacokinetics reported in trial publications; not an approved drug.