Development of tight junction modulators for drug delivery to the brain

• Project/Area Number: 18K19400
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Kondoh Masuo 大阪大学, 薬学研究科, 教授 (50309697)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: タイトジャンクション

Outline of Final Research Achievements

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 tight junctions (TJs). The TJ seal prevents the paracellular diffusion of drugs into the CNS.
In the present study, we firstly generated TJ modulators, and secondly examined the effects of the TJ modulators on the BBB in vitro and in vivo. We finally found that one of the TJ modulators may be a potential lead for the development of novel drug delivery system targeting the CNS.

Academic Significance and Societal Importance of the Research Achievements

周知のように、高齢社会の到来に伴い、認知症などの中枢性神経(CNS)疾患が指数関数的に増加しているものの、脳血管に存在する血液脳関門が脳内への薬物透過のバリアとして機能しているため、単に薬を投与しても脳内には送達されず、ここにCNS薬開発の難しさがある。
本研究で開発したTJシールド制御技術は、サルにおいて副作用を伴うことなく脳内薬物送達活性を示していたことから、将来的にアルツハイマー病や血管性認知症等のCNS薬開発に貢献できると考えられる。