Prevention of progressive dementia by drug-repositioning of rifampicin

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07847
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Osaka City University
• Principal Investigator: Umeda Tomohiro 大阪市立大学, 大学院医学研究科, 特任講師 (70549790)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経変性疾患 / 認知症 / タウ / 予防薬・治療薬 / リファンピシン / 神経病理伝播

Outline of Final Research Achievements

Tau propagation is a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD). Recent studies suggest that tau oligomers participate in this process. We have showed that intranasal rifampicin (RFPi.n.) inhibits tau oligomer accumulation in mice. In this study, we examined the effects of RFPi.n. on tau propagation in a new mouse model. A tau oligomer-rich frc. prepared from the brain of an AD patient was injected into a unilateral hippocampus of Tau264 mice that express both 3R- and 4R-WT human tau. RFPi.n. was started 1 week after the injection and performed 3 times a week for 24 weeks. Cognitive function and tau pathology were assessed by the Morris water maze test and IHC. RFPi.n. inhibited the spreading of tau oligomers and neurofibrillary tangle formation. Synapse and neuronal loss were also prevented, and cognitive function remained normal. The results suggest that RFPi.n. could be a promising remedy that halts the progression of tauopathy.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

経鼻rifampicinはtau病理伝播を抑制することで、脳内変性領域の拡大と記憶障害を阻止した。経鼻rifampicinが、病理形成前での予防的効果だけでなく、疾患発症後の進行をも抑止できる可能性が示された。Drug repositioningによる効果的かつready-to-useな認知症予防薬・治療薬となりえる。