Tight junction regulator

Larazotide is an eight-amino-acid peptide that tightens the junctions between intestinal cells. The logic for coeliac disease is specific: gluten peptides reach the lamina propria partly by passing between enterocytes through junctions that gluten itself loosens, so a drug that keeps those junctions shut should blunt the reaction. It is the most clinically advanced non-dietary coeliac treatment there has been, and it has an unusual record: the trial that met its primary endpoint did so at the lowest of three doses, with 1 mg and 2 mg no different from placebo. Earlier gluten-challenge trials failed on permeability, their actual primary endpoint, while showing symptom benefit. A phase 3 programme followed and has not delivered an approved drug.