Larazotide acetate is a synthetic peptide. Larazotide acetate acts as a tight junction regulator and reverses leaky junctions to their normally closed state.
Tight junctions (TJs) are located at the apico-lateral borders of adjoining epithelial cells, regulating the patency of the paracellular space and limiting the bidirectional diffusion of particles, water, and solutes across mucosal surfaces. Larazotide acetate, an 8-mer peptide, acts as a tight junction regulator and inhibits the cellular changes elicited by gliadin fragments, AT-1002, and cytokines. In Caco-2 cells, larazotide acetate at 15 and 12.5 mM significantly inhibited the AT-1002-induced increase in LY passage by 71 and 38%, respectively. PTG-induced ZO-1 redistribution was inhibited by larazotide acetate (12.5 mM; 1 h) and the junctional ZO-1 fluorescence intensity was maintained at near control levels. Furthermore, in IEC6 cells treated with PTG and larazotide acetate (12.5 mM), the actin network was protected from disassembly. In vivo, larazotide acetate inhibited gliadin-induced macrophage accumulation in the intestine and preserved normal tight junction structure in gliadin-sensitized HLA-HCD4/DQ8 double transgenic mice[2].
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