Larazotide

Larazotide (AT-1001) is a synthetic octapeptide derived from the Vibrio cholerae zonula occludens toxin (Zot), designed to act as a competitive inhibitor of the zonulin pathway that regulates intestinal tight junction permeability. By blocking zonulin's action, larazotide prevents the increase in intestinal permeability that allows harmful substances to cross the gut barrier.

The zonulin system represents an endogenous pathway regulating paracellular permeability between intestinal epithelial cells. In celiac disease, gluten-derived peptides trigger zonulin release, opening tight junctions and allowing gluten peptides to access the lamina propria where they initiate the inflammatory immune response characteristic of the disease.

Larazotide is designed for oral administration to act locally in the gut lumen, preventing zonulin-mediated tight junction opening without systemic absorption. Clinical trials in celiac patients have shown the peptide reduces gluten-induced symptoms and intestinal permeability markers when taken with meals containing gluten.

Beyond celiac disease, larazotide's mechanism has research applications in conditions involving increased intestinal permeability, including inflammatory bowel disease, irritable bowel syndrome, and the broader concept of 'leaky gut.' The compound provides a tool for investigating the role of paracellular permeability in various gastrointestinal and systemic conditions.