Also known as: AT-1001 · INN-202
Larazotide is a synthetic 8-amino-acid peptide derived from zonula occludens toxin (ZOT) from Vibrio cholerae. It acts as a tight junction regulator, blocking the zonulin-mediated increase in intestinal permeability that drives celiac disease and leaky gut syndrome.
Larazotide acetate (AT-1001) was developed by Alba Therapeutics and has progressed through Phase 2b clinical trials for celiac disease. It is the most clinically advanced tight junction regulator in development, with a well-characterized mechanism and established safety profile in human trials.
The peptide works by competitively blocking zonulin receptors on intestinal epithelial cells. Zonulin is a protein that opens tight junctions — the molecular seals between intestinal cells — and is elevated in celiac disease, type 1 diabetes, and non-alcoholic fatty liver disease. By preventing zonulin binding, larazotide keeps tight junctions closed, reducing antigen translocation and immune activation.
Larazotide acts as a competitive antagonist at zonulin receptors (PAR2 and EGF receptors) on enterocytes, preventing the zonulin-induced phosphorylation of ZO-1 and occludin that causes tight junction disassembly. This directly reduces intestinal permeability.
By maintaining barrier integrity, larazotide prevents gluten peptides (specifically the 33-mer immunogenic fragment) from translocating into the lamina propria, reducing dendritic cell activation and downstream T-cell-mediated intestinal damage in celiac patients.
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