Larazotide acetate is a first-in-class tight junction (TJ) regulator under development as an adjunct to a GFD. Larazotide acetate is a novel, locally acting non-systemic, synthetic 8-amino acid oral peptide, discovered during functional screening of synthetic Vibrio cholera related peptides. 8– 10 An intestinal permeability-inflammation loop is established, leading to a multitude of gastrointestinal and systemic manifestations.
8 Increased permeability promotes gluten peptide transport to gut-associated lymphoid tissue, initiating inflammatory cytokine release and T-cell recruitment. In CeD, paracellular permeability is increased by an inflammatory response to gluten entry into the intestinal mucosa. 5, 6 While persistent symptoms may have a variety of causes, one potential source is sporadic gluten exposure, 7 which may contribute to persistent enteropathy, continued symptoms, and reduced quality of life. 3, 4 Recurrent CeD signs and symptoms due to inadvertent or deliberate gluten exposure have been reported in approximately 70% of CeD patients on a GFD.
1, 2 CeD is triggered by ingestion of gluten-containing foods and managed by a gluten-free diet (GFD). Celiac disease (CeD), a genetic autoimmune condition, affects ~1% of the western population.
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