| Project/Area Number |
17K19487
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmaceutical Sciences and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
樋野 展正 大阪大学, 薬学研究科, 助教 (90469916)
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| Research Collaborator |
KONDOH masuo
TAKEDA hiroyuki
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 血液脳関門 / Claudin-5 / 抗体 / 血管内皮細胞 / 薬学 / DDS / 血管生物学 |
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| 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.
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| 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。
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