Larazotide

Synthetic octapeptide tight-junction regulator (AT-1001) investigated in randomized trials for persistent celiac disease symptoms.

Overview

Larazotide (formerly AT-1001) is a synthetic octapeptide derived from the zonula occludens toxin of Vibrio cholerae. It is designed to inhibit the reversible opening of intestinal tight junctions, and it has been investigated as an adjunct for celiac disease in patients who continue to have symptoms despite a gluten-free diet. Several randomized placebo-controlled trials have been completed, with results suggesting modest effects on symptom control but no restoration of full mucosal protection against gluten.

Mechanism

Larazotide is proposed to block the signaling that leads to disassembly of intestinal epithelial tight junctions after gluten exposure, thereby reducing paracellular passage of gluten peptides and downstream immune activation in susceptible individuals. It acts at the intestinal epithelium rather than on the gluten antigen itself.

Dosing

In published clinical trials larazotide was administered orally in capsule form, several times daily before meals, at doses defined by each study protocol. It remains investigational and is not an approved medicine.

Expected Effects

reductions in gluten-induced symptom scores in some randomized trials in celiac disease
limited or inconsistent effects on intestinal mucosal damage markers across trials

Side Effects & Tolerability

The trial data indicate that larazotide was generally well tolerated, with gastrointestinal complaints the most commonly reported events. Long-term safety data remain limited.

Storage

Investigational supplies are handled per the study sponsor's protocol; no consumer storage guidance applies to an unapproved drug.