TY - JOUR T1 - Claudin-5-Binders Enhance Permeation of Solutes across the Blood-Brain Barrier in a Mammalian Model JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 275 LP - 283 DO - 10.1124/jpet.117.243014 VL - 363 IS - 2 AU - Yosuke Hashimoto AU - Keisuke Shirakura AU - Yoshiaki Okada AU - Hiroyuki Takeda AU - Kohki Endo AU - Maki Tamura AU - Akihiro Watari AU - Yoshifusa Sadamura AU - Tatsuya Sawasaki AU - Takefumi Doi AU - Kiyohito Yagi AU - Masuo Kondoh Y1 - 2017/11/01 UR - http://jpet.aspetjournals.org/content/363/2/275.abstract N2 - A current bottleneck in the development of central nervous system (CNS) drugs is the lack of drug delivery systems targeting the CNS. The intercellular space between endothelial cells of the blood-brain barrier (BBB) is sealed by complex protein–based structures called tight junctions (TJs). Claudin-5 (CLDN-5), a tetra-transmembrane protein is a key component of the TJ seal that prevents the paracellular diffusion of drugs into the CNS. In the present study, to investigate whether CLDN-5 binders can be used for delivery of drugs to the CNS, we generated monoclonal antibodies (mAbs) specific to the extracellular domains of CLDN-5. In an in vitro model of the BBB, the anti–CLDN-5 mAbs attenuated trans-epithelial/endothelial electrical resistance and enhanced solute permeation. These anti–CLDN-5 mAbs are potential leads for the development of novel drug delivery systems targeting the CNS. ER -