2011 Fiscal Year Final Research Report
Development of a new and effective DNA vaccine for Alzheimer's disease
| Project/Area Number |
21591103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | 財団法人東京都医学総合研究所 (2011)
Tokyo Metropolitan Organization for Medical Research (2009-2010) |
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Principal Investigator |
OKURA Yosio 財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員 (10392367)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Yoh 財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員
KOHYAMA Kuniko 財団法人東京都医学総合研究所, 基盤技術研究センター, 基盤技術研究職員
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| Project Period (FY) |
2009 – 2011
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| Keywords | アルツハイマー病 / DNAワクチン / Aベータ |
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| Research Abstract |
<Background> It is recently known that in Alzheimer disease, not only Aβoligomers, but also posttranslationally modified Aβspecies and other amyloidogenic peptides are neurotoxic. In the present study, we have attempted to develop a new DNA vaccine targeting these molecules.
<Materials and Methods> Characterization of a newly developed DNA vaccine(Code name, YM3711) was performed in in vitro and in vivo studies. Aβproduction and Aβsecretion abilities were evaluated using YM3711-transfected cultured cells. Anti-Aβand anti-Aβspecies antibody-inducing and Aβ-reducing abilities were determined using plasma and brains from YM3711-vaccinated animals.
<Results> YM3711-transfected cells produced 5-6 fold larger amount of Aβand secreted Aβ3-4 fold higher in the culture supernatant compared with previous DNA vaccines. When vaccinated to mice and rabbits, YM3711 induced not only anti-Aβantibodies, but also antibodies against Aβspecies and amyloidogenic peptides. Importantly, YM3711 vaccination induced reduction of Aβand Aβspecies in model mice.
<Conclusion> Based on the findings, we are currently performing preclinical trials of YM3711.
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