A novel technology for regulating blood brain barrier

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19487
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pharmaceutical Sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Okada Yoshiaki 大阪大学, 薬学研究科, 准教授 (50444500)
• Co-Investigator(Kenkyū-buntansha): 樋野 展正 大阪大学, 薬学研究科, 助教 (90469916)
• Research Collaborator: KONDOH masuo ; TAKEDA hiroyuki
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 血液脳関門 / Claudin-5 / 抗体 / 血管内皮細胞

Outline of Final Research Achievements

The blood-brain barrier function of the cerebrovascular system protects the brain by preventing foreign matter from entering the brain. On the other hand, the blood-brain barrier also hinders the transfer of drugs to the brain, which hinders the development of drugs for treating brain diseases. In this study, we aimed to develop a technology to temporarily loosen the blood-brain barrier for the effective drug delivery to the brain. Since the blood-brain barrier is generated by tight junction of vascular endothelial cells, we generated anti-human Claudin-5 antibodies that inhibit the junction. In addition, in order to evaluate the blood-brain barrier control activity of these antibodies, we generated mice having human Claudin-5 and obtained data suggesting that the anti-Claudin-5 antibodies have the activity of loosening the blood-brain barrier.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の我が国ではアルツハイマー病など脳疾患の患者が増加の一途を辿っている。製薬企業の努力にもかかわらず、脳疾患治療薬の開発が難航する理由の一つに、薬の脳移行を妨げる血液脳関門の存在がある。本来、血液脳関門は、脳を異物侵入から守る生体防御機構であるが、脳疾患の薬の脳への移行も阻害してしまうため、優れた治療薬の候補分子が、脳に移行しないという理由で薬にならないという現状がある。我々の今回の研究は、血液脳関門を緩め、脳に効率よく薬を届ける技術の開発研究であり、今後の脳疾患治療薬開発に貢献すると期待される。