Development of a new treatment for Alzheimer's disease targeting GM1 ganglioside

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15369
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kumamoto University
• Principal Investigator: Kajihara Ryutaro 熊本大学, 大学院生命科学研究部(保), 助教 (00738221)
• Project Period (FY): 2021-11-01 – 2023-03-31
• Keywords: アルツハイマー病

Outline of Final Research Achievements

Alzheimer's disease (AD) accounts for 60-70% of all dementias and has the highest financial cost in developed countries. The aggregation and accumulation of peptides called Aβ in the brain is thought to be the pathogenic mechanism of this disease, but no fundamental treatment has been established so far, and only symptomatic treatment is available. In recent years, it has become clear that a glycolipid called GM1 ganglioside (GM1), which exists on the surface of neuronal cell membranes in AD patients, promotes Aβ aggregation and is deeply involved in the pathogenesis of AD. In this study, we will develop a new therapeutic drug for AD with a novel mechanism of action targeting GM1 and elucidate the function of GM1 in the pathogenesis of AD by using iPS cell technology.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

家族性AD患者からiPS細胞を樹立し神経細胞へと分化させることによって、in vitroでヒト神経細胞を解析でき、種の違い・アーティファクト等の問題を起こしにくい実験系を確立した。また、根本的な治療薬が存在しない本疾患において、GM1をターゲットとして新規治療薬開発を行うことは非常に独創的である。さらに、GM1ガングリオシドーシス患者由来iPS 細胞を用いたスクリーニング系により、GM1を抑制する化合物を世界で初めて発見したことは非常にインパクトが大きい。本研究によって今までにない作用機序によるAD治療薬を開発でき、将来的に医療現場における患者のQOL の向上に貢献できる。