Development of nuclear medical imaging probes that target alfa-synuclein in Parkinson's disease

Research Project

Project/Area Number	17H04260
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Radiation science
Research Institution	Kyoto University
Principal Investigator	Ono Masahiro 京都大学, 薬学研究科, 教授 (80336180)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000) Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000) Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords	α-synuclein / imaging / Parkinson's disease / αシヌクレイン / イメージング / パーキンソン病 / プローブ
Outline of Final Research Achievements	Parkinson’s disease (PD) is one of major neurodegenerative disorders. It is generally known that Lewy body composed of α-synuclein aggregates shows high toxicity to neuronal cells. The aim of this study is to develop nuclear medical imaging probes that specifically bind to α-synuclein aggregates deposited in the brain of PD patients. We designed and synthesized some candidate compounds as α-synuclein imaging probes, and evaluated their utility by performing in vitro and in vivo experiments. The development of this new molecular imaging technique may lead to not only early diagnosis of PD but also elucidation of pathogenesis and development of therapeutics of PD.
Academic Significance and Societal Importance of the Research Achievements	本研究で開発する新規プローブを用いたαシヌクレインの生体イメージングが可能となれば，パーキンソン病(PD)の早期診断への応用が期待できる．さらに，アミロイドイメージングおよびタウイメージングと組み合わせた, 生体融合脳イメージングによる鑑別診断への応用も可能になると考えられる．治療薬のスクリーニングのツールとしても応用可能であることから，αシヌクレインを標的分子とするPDの創薬研究への貢献も期待できる．さらに，αシヌクレイン凝集体は，認知症の中でも患者数の多いレビー小体型認知症(DLB)においても観察される病理学的変化であり， DLBの診断・創薬研究への応用の可能性も秘めている．