Sensitive detection of abnormal prion protein in genetic human prion diseases

2014 Fiscal Year Final Research Report

• Project/Area Number: 23300127
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Nagasaki University
• Principal Investigator: ATARASHI Ryuichiro 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90452846)
• Co-Investigator(Renkei-kenkyūsha): NISHIDA Noriyuki 長崎大学, 医歯薬学総合研究科(医学系), 教授 (40333520) ; SATOH Katsuya 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (70398147)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 神経変性疾患 / 遺伝性プリオン病

Outline of Final Research Achievements

The genetic form of human Prion diseases (gPrD) is caused by mutations in the prion protein gene. We recently developed a highly sensitive amplification　technology, designated real-time quaking-induced conversion (RT-QUIC). In this study, we evaluated RT-QUIC assay in patients with gPrD, as a diagnostic tool. The detection sensitivities of RT-QUIC were as follows: GSS(78%), FFI(100%), gCJD E200K(87%). In contrast, the detection sensitivities of biomarkers were considerably lower: GSS(11%), FFI(0%), gCJD E200K(73%). Thus, RT-QUIC had a much higher detection sensitivity compared with testing for biomarkers. Moreover, we evaluated the effect of FK506 on prion infection, using cell culture and animal models. We found that FK506 reduced PrPSc and increased the formation of autolysosome in prion-infected cells. The survival periods in prion-inoculated mice were significantly increased when FK506 was administered. These findings show that FK506 could constitute a novel anti-prion drug.

Free Research Field

神経解剖学・神経病理学