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2018 Fiscal Year Final Research Report

Development of drugs for cerebral amyloidosis with novel mechanisms of action using DDS technology

Research Project

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Project/Area Number 16H05223
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKumamoto University

Principal Investigator

ARIMA HIDETOSHI  熊本大学, 大学院生命科学研究部(薬), 教授 (50260964)

Co-Investigator(Kenkyū-buntansha) 東 大志  熊本大学, 大学院先導機構, 准教授 (20613409)
本山 敬一  熊本大学, 大学院生命科学研究部(薬), 准教授 (50515608)
Research Collaborator Yokoyama Ryoma  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords脳アミロイドーシス / シクロデキストリン / デンドリマー / 結合体 / ドラッグデリバリーシステム / アミロイド溶解作用 / 血液脳関門 / 脳移行性
Outline of Final Research Achievements

So far, the number of patients with dementia has been increasing, especially Alzheimer's disease (AD) will be more serious. However, there is no curative treatments to AD, so development of new therapeutic agents is strongly desired. In this study, brain-targeting PAMAM dendrimer/cyclodextrin conjugate (BT-CDE conjugate) was prepared and was found to simultaneously regulate not only the formation and accumulation of amyloid fibrils but also accumulation of cholesterol in cells. In addition, intravenous administration of BT-CDE conjugate to mice showed higher brain-localizing properties than CDE conjugate. These results suggest that BT-CDE may have the potential as new drug seeds for AD.

Free Research Field

応用薬理学 製剤学 薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究で見出したラクトシル化CDE結合体は、患者数の増加が予想されているアルツハイマー病に対して、これまでに開発されてきた化合物とは化学構造が全く異なり、また、ADに関わる複数の因子を同時に制御可能な全く新規の治療薬シーズとなりうる可能性が示された。この研究成果はすでに特許出願を行っており、日本初のAD治療薬になりうることが期待される。

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Published: 2020-03-30  

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