Larazotide Acetate
clinical trialsAlso known as: AT-1001, INN-202
**Mechanism of Action** Larazotide acetate (AT-1001, INN-202) is a synthetic octapeptide that functions as a tight junction regulator. It inhibits zonulin-mediated disassembly of intercellular tight junctions in intestinal epithelial cells, thereby reducing paracellular permeability. By preventing the opening of tight junctions triggered by gliadin (a gluten component) or other stimuli, larazotide attenuates the passage of immunogenic peptides and microbial products across the gut barrier, mitigating local and systemic inflammatory responses. **Key Research Findings** Clinical trials have demonstrated that larazotide acetate reduces intestinal permeability and gluten-induced symptoms in patients with celiac disease who are on a gluten-free diet. Phase 2 and 3 studies showed significant improvements in gastrointestinal symptom scores (e.g., bloating, abdominal pain) and reductions in urinary lactulose/mannitol ratios, a marker of gut barrier integrity. However, results have been mixed; some trials failed to meet primary endpoints for histologic or serologic outcomes (e.g., anti-tissue transglutaminase antibodies). Larazotide does not degrade gluten or inhibit its immunogenic peptides but acts prophylactically to limit mucosal exposure. **Clinical Relevance** Larazotide acetate is the first-in-class tight junction regulator developed as an adjunctive therapy for celiac disease, intended for use alongside a gluten-free diet to manage breakthrough symptoms and accidental gluten exposure. It has not yet received FDA approval; ongoing research explores its utility in other conditions characterized by increased intestinal permeability, such as inflammatory bowel disease and irritable bowel syndrome. The peptide’s safety profile appears favorable, with mild gastrointestinal adverse events reported. For research purposes only — not medical advice.
Key data
C34H59N9O12Research & studies
Increased intestinal permeability is central to coeliac disease pathophysiology.; Mechanisms involve zonulin, inflammatory cytokines, microbial alterations, and immune responses to gliadin.; Therapies targeting barrier integrity include diets, supplements, and experimental drugs like larazotide acetate and IMU-856.; Reliable biomarkers for permeability and further research on barrier-normalizing therapies are needed.
HSMP-LA exhibited robust muco-adhesion, prolonged retention, and sustained-release of larazotide acetate, shielding epithelium from pathogens and toxins.; Sustained-release larazotide selectively inhibited zonulin-mediated tight junction disruption via MLCK/p-MLC signals in LPS-injured Caco-2 cells.; In DSS-induced colitis mice, HSMP-LA significantly reduced disease activity, suppressed pro-inflammatory cytokines, and upregulated anti-inflammatory IL-10.; HSMP-LA repaired tight junctions (ZO-1, occludin, claudin-5), restored mucus production (MUC2), and rebalanced gut microbiota.
For celiac disease, gluten-degrading enzymes (latiglutenase, Kuma030), zonulin inhibitors (larazotide acetate), and transglutaminase 2 inhibitors (ZED-1227) show promise but require further validation in children.; In eosinophilic esophagitis, biologics like dupilumab and IL-13/IL-5 inhibitors show varying efficacy, with more pediatric research needed.; For inflammatory bowel disease, emerging treatments include biologics (vedolizumab, ustekinumab, risankizumab) and small molecules (tofacitinib, etrasimod, upadacitinib), guided by personalized therapy.; New medications for refractory or steroid-dependent autoimmune hepatitis are being explored, but pediatric-specific data remain limited.
Endothelial TJ disruption occurs early (5-10 days) before TAAD formation in BAPN mice.; MRI probes (FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd) non-invasively detected early TJ dysfunction and predicted TAAD development.; AT-1001, a protease-activated receptor 2 inhibitor, sealed TJs and reduced TAAD incidence.; Endothelial-targeted ZO-1 conditional knockout increased TAAD incidence, confirming TJ role in protection.
Frequently asked questions
What is Larazotide Acetate?
**Mechanism of Action** Larazotide acetate (AT-1001, INN-202) is a synthetic octapeptide that functions as a tight junction regulator. It inhibits zonulin-mediated disassembly of intercellular tight junctions in intestinal epithelial cells, thereby reducing paracellular permeability. By preventing the opening of tight
How does Larazotide Acetate work?
Tight-junction-regulating octapeptide that reduces intestinal permeability ('leaky gut'); trialed as an adjunct for celiac disease.
What is the research status of Larazotide Acetate?
Larazotide Acetate is currently classified as clinical trials, with 44 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Larazotide Acetate?
Larazotide Acetate has a molecular weight of approximately 785.9 g/mol (formula C34H59N9O12).
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