Development of drug delivery system for treatment of central nervous system diseases targeting tight junctions

One of the main obstacles for the drug development for central nervous system disease is the strong tight junction-seals in the blood-brain barrier (BBB). Claudin-5 (CLDN-5) is the essential protein for tight junction in the BBB, which restricts the influx of small molecules up to 1 kDa. Many researchers have attempted to develop methodologies to selectively inhibit the CLDN-5 dependent tight junction and open the BBB. Recently, our group successfully developed anti-CLDN-5 monoclonal antibodies that inhibit the barrier function of CLDN-5. In this review, we introduce the characteristics of our anti-CLDN-5 monoclonal antibodies, and discuss potential of tight junction modulators for treating central nervous system diseases.