Dr. Margaret Neville and her research team have developed a novel peptide that targets and disrupts claudins, a family of tight junction proteins. Dr. Neville has shown that disruption of claudins initiates a cellular signaling cascade that activates the death receptor pathway causing apoptosis of epithelial cells. This disruption caused a seven-fold increase in cellular removal and apoptosis, an effect much more potent than that produced by other tight junction-inhibitory peptides described to date. Moreover, the physiological property of transepithelial electrical resistance remained stable during the increase in apoptosis, preventing breakdown of the epithelial separations necessary for proper organ function. In a separate set of experiments examining potency of the newest version of the claudin peptide, Dr. Neville demonstrated that overnight incubation of epithelial cells with 1mM of the claudin disrupting peptide caused 25% cell death. At a concentration of 2mM, 100% apoptosis was achieved.
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