2018 Fiscal Year Final Research Report
Therapeutic vaccine for white matter lesion and amyloid in vascular dementia model in rat;
Project/Area Number |
16K09232
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General internal medicine(including psychosomatic medicine)
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Research Institution | The University of Tokyo |
Principal Investigator |
Wakayama Kouji 東京大学, 医学部附属病院, 特任助教 (50349263)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Keywords | 脳血管性認知症 / ワクチン療法 / Angiotensin II |
Outline of Final Research Achievements |
We investigated the efficacy of Angiotensin II (Ang II) peptide vaccine against vascular dementia (VD) using 2 vessel occlusion (2VO) rat which is the rat model of VD. We demonstrated that vaccinated rats presented reduced astrocytes and microglia and amelioration of oligodendrocytes depletion in the white matter lesion as well as improvement of cognitive deficit. We observed no difference in expression level of β-amyloid precursor protein gene and β secretase-1 gene at a maximum observation period of 56 days, thus we tried to elucidate whether white matter protection induced by Ang II vaccination related to the differentiation of oligodendrocyte. Our findings suggested that the efficacy of Ang II vaccine was related with increased expression of endothelial FGF2 through endothelial protection by Ang II blockade. Endothelial FGF2 was considered to induce cAMP response element binding protein activation and the differentiation of the oligodendrocyte lineage cells.
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Free Research Field |
脳血管障害の基礎研究
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Academic Significance and Societal Importance of the Research Achievements |
自己抗原を標的としたワクチン治療は慢性疾患に対する新たな治療手段として注目されている。認知症のワクチン治療としてはアミロイドβを標的としたアルツハイマー病のワクチン療法が有名であるが、脳炎の合併という重大な副作用が生じたことで開発が滞った。Angiotensin IIを標的としたワクチン療法は高血圧ワクチン療法として実用化を目指しすでに治験が進行中であることからも安全性の高い治療手段と考えられる。我が国では認知症の原因疾患としてアルツハイマー型認知症に次いで多い脳血管性認知症の安全かつ有効性の高い治療法の確立は重要な課題であり、本研究の進展は学術的のみならず社会的にもその意義は大きいといえる。
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