Development of innovative non-invasive diagnostic methods for prion disease

• Project/Area Number: 17K09759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagasaki University
• Principal Investigator: SATOH Katsuya 長崎大学, 医歯薬学総合研究科(保健学科), 教授 (70398147)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 神経変性疾患 / プリオン病 / 異常プリオン蛋白の半定量化 / 臓器 / RT-QuIC法 / 非侵襲組織 / 異常プリオン蛋白を / バイオマーカー / 非侵襲 / 消化管 / 髄液 / 血液 / 各臓器 / 診断 / 蛋白質 / 診断法

Outline of Final Research Achievements

Human prion disease (HPD) is 100% lethal rapidly progressive dementia, and no diagnostic or therapeutic method for HPD has yet been established. We have succeeded for the first time in the world in detecting the abnormal prion proteins in the CSF of patients with HPD. The purpose of this study is to attempt an innovative and non-invasive diagnosis of HPD from non-CNS organs containing blood ahead of the rest of the world. From 2017 to March　2021 , based on the research results so far, an epoch-making diagnostic method was established based on four studies. （1） Establish semi-quantification of trace amounts of abnormal prion protein, especially in human samples. (2)Analysis of stored samples and 4-year retrospective study will be conducted to establish sensitivity and specificity for diagnosis from CSF, and semi-quantification will also be performed. (3) We developed a new detection method for abnormal prion proteins from samples of HPD patients, and examined its effectiveness.

Academic Significance and Societal Importance of the Research Achievements

プリオン病は100%の致死性急速進行性認知症であり、プリオン病の診断法・治療法は未だ確立されていない。我々はプリオン病患者髄液中の超微量の異常プリオン蛋白の検出に世界で初めて成功した。本研究は世界に先んじて血液を含んだ非中枢神経の臓器からのプリオン病の革新的かつ非侵襲的な診断を試みた。プリオン病患者のサンプル（血清・各種臓器）からの異常プリオン蛋白の新規検出法を開発し、その有効性について検討を行った。特に非侵襲性組織からプリオン活性の検出法に成功し、プリオン病の治験の実施が可能になれば実験計画の達成への期待が高まる。

Research Products

• [Int'l Joint Research] University Medical Center Gottingen(ドイツ)
• [Int'l Joint Research] University of California/Case Western Reserve University/Laboratory of Persistent Viral Diseases(米国)
• [Int'l Joint Research] University of Melbourne(オーストリア)
• [Int'l Joint Research] University of Toronto(カナダ)
• [Int'l Joint Research] Istituto Superiore di Sanita(イタリア)
• [Int'l Joint Research]
• [Int'l Joint Research] Melbourne University(オーストラリア)
• [Int'l Joint Research] HAllym University(韓国)
• [Int'l Joint Research] Melbourne University(オーストラリア)
• [Int'l Joint Research] Hallym University(韓国)
• [Journal Article] The Latest Research on RT-QuIC Assays-A Literature Review (2021)
  • Author(s): Dong TT, Satoh K.
  • Journal Title: Pathogens Volume: 10(3) Issue: 3 Pages: 305-305
  • DOI: 10.3390/pathogens10030305
  • Peer Reviewed / Open Access
• [Journal Article] Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease (2021)
  • Author(s): Hermann Peter、Appleby Brian、Brandel Jean-Philippe、Caughey Byron、Collins Steven、Geschwind Michael D、Green Alison、Haik Stephane、Kovacs Gabor G、Ladogana Anna、Llorens Franc、Mead Simon、Nishida Noriyuki、Pal Suvankar、Parchi Piero、Pocchiari Maurizio、Satoh Katsuya、Zanusso Gianluigi、Zerr Inga
  • Journal Title: The Lancet Neurology Volume: 20 Issue: 3 Pages: 235-246
  • DOI: 10.1016/s1474-4422(20)30477-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt?Jakob disease (2021)
  • Author(s): Honda Hiroyuki、Mori Shinichiro、Watanabe Akihiro、Sasagasako Naokazu、Sadashima Shoko、??ng Trang、Satoh Katsuya、Nishida Noriyuki、Iwaki Toru
  • Journal Title: Neuropathology Volume: 41 Issue: 2 Pages: 152-158
  • DOI: 10.1111/neup.12717
  • Peer Reviewed / Open Access
• [Journal Article] V180I genetic Creutzfeldt-Jakob disease with cardiac sympathetic nerve denervation masquerading as Parkinson's disease: A case report (2021)
  • Author(s): Fujita H, Ogaki K, Shiina T, Onuma H, Sakuramoto H, Satoh K, Suzuki K.
  • Journal Title: Medicine (Baltimore) Volume: 100(2) Issue: 2 Pages: e24294-e24294
  • DOI: 10.1097/md.0000000000024294
  • Peer Reviewed / Open Access
• [Journal Article] Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue (2021)
  • Author(s): Nakashima A, Moriuchi T, Matsuda D, Hasegawa T, Nakamura J, Anan K, Satoh K, Suzuki T, Higashi T, Sugawara K.
  • Journal Title: Neural Regen Res Volume: 16(6) Issue: 6 Pages: 1031-1036
  • DOI: 10.4103/1673-5374.300448
  • Peer Reviewed / Open Access
• [Journal Article] Concurrent Validity of the ABC Dementia Scale with Other Standard Scales: A New Comprehensive Instrument for Assessing Dementia in Japan (2020)
  • Author(s): Wataru Shimoda, Jun Murata, Akira Nakatani, Katsuya Satoh
  • Journal Title: Dementia and Geriatric Cognitive Disorders Volume: 49 Issue: 6 Pages: 617-627
  • DOI: 10.1159/000513485
  • Peer Reviewed / Open Access
• [Journal Article] A patient with spastic paralysis finally diagnosed as V180I genetic Creutzfeldt-Jakob disease 9 years after onset (2020)
  • Author(s): Nomura Taichi、Iwata Ikuko、Naganuma Ryoji、Matsushima Masaaki、Satoh Katsuya、Kitamoto Tetsuyuki、Yabe Ichiro
  • Journal Title: Prion Volume: 14 Issue: 1 Pages: 226-231
  • DOI: 10.1080/19336896.2020.1823179
  • Peer Reviewed / Open Access
• [Journal Article] MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type (2020)
  • Author(s): Hamaguchi T, Sanjo N, Ae R, Nakamura Y, Sakai K, Takao M, Murayama S, Iwasaki Y, Satoh K, Murai H, Harada M, Tsukamoto T, Mizusawa H, Yamada M.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 91 Issue: 11 Pages: 1158-1165
  • DOI: 10.1136/jnnp-2020-323231
  • Peer Reviewed / Open Access
• [Journal Article] Administration of FK506 from Late Stage of Disease Prolongs Survival of Human Prion-Inoculated Mice (2020)
  • Author(s): Takehiro Nakagaki, Daisuke Ishibashi, Tsuyoshi Mori, Yukiko Miyazaki, Hanae Takatsuki, Hiroya Tange, Yuzuru Taguchi, Katsuya Satoh, Ryuichiro Atarashi, Noriyuki Nishida
  • Journal Title: Neurotherapeutics Volume: 17(4) Issue: 4 Pages: 1850-1860
  • DOI: 10.1007/s13311-020-00870-1
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological findings of a long-term survivor of V180I genetic Creutzfeldt-Jakob disease (2020)
  • Author(s): Hayashi Yuichi、Iwasaki Yasushi、Waza Masahiro、Kato Shinei、Akagi Akio、Kimura Akio、Inuzuka Takashi、Satoh Katsuya、Kitamoto Tetsuyuki、Yoshida Mari、Shimohata Takayoshi
  • Journal Title: Prion Volume: 14 Issue: 1 Pages: 109-117
  • DOI: 10.1080/19336896.2020.1739603
  • Peer Reviewed / Open Access
• [Journal Article] MM2 cortical form of sporadic Creutzfeldt-Jakob disease without progressive dementia and akinetic mutism: A case deviating from current diagnostic criteria (2020)
  • Author(s): Takahashi-Iwata Ikuko、Yabe Ichiro、Kudo Akihiko、Eguchi Katsuya、Wakita Masahiro、Shirai Shinichi、Matsushima Masaaki、Toyoshima Takanobu、Chiba Susumu、Tanikawa Satoshi、Tanaka Shinya、Satoh Katsuya、Kitamoto Tetsuyuki、Sasaki Hidenao
  • Journal Title: Journal of the Neurological Sciences Volume: 412 Pages: 116759-116759
  • DOI: 10.1016/j.jns.2020.116759
  • NAID: 120007036450
  • Peer Reviewed / Open Access
• [Journal Article] Prion protein interacts with the metabotropic glutamate receptor 1 and regulates the organization of Ca2+ signaling (2020)
  • Author(s): Matsubara Takehiro、Satoh Katsuya、Homma Takujiro、Nakagaki Takehiro、Yamaguchi Naohiro、Atarashi Ryuichiro、Sudo Yuka、Uezono Yasuhito、Ishibashi Daisuke、Nishida Noriyuki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 525 Issue: 2 Pages: 447-454
  • DOI: 10.1016/j.bbrc.2020.02.102
  • Peer Reviewed / Open Access
• [Journal Article] Correction to: Intra-Arterial Transplantation of Low-Dose Stem Cells Provides Functional Recovery Without Adverse Effects After Stroke (2020)
  • Author(s): Fukuda Y, Horie N, Satoh K, Yamaguchi S, Morofuji Y, Hiu T, Izumo T, Hayashi K, Nishida N, Nagata I.
  • Journal Title: Cell Mol Neurobiol Volume: 40(6) Issue: 6 Pages: 1057-1057
  • DOI: 10.1007/s10571-020-00798-2
  • Peer Reviewed / Open Access
• [Journal Article] Cortical Hyperintensity on Diffusion-weighted Images as the Presymptomatic Marker of Sporadic Creutzfeldt-Jakob Disease (2019)
  • Author(s): Maeda K, Sugihara Y, Shiraishi T, Hirai A, Satoh K
  • Journal Title: Internal Medicine Volume: 58 Issue: 5 Pages: 727-729
  • DOI: 10.2169/internalmedicine.1155-18
  • NAID: 130007607145
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-03-01
  • Peer Reviewed
• [Journal Article] Postmortem Quantitative Analysis of Prion Seeding Activity in the Digestive System (2019)
  • Author(s): Satoh K, Fuse T, Nonaka T, Dong T, Takao M, Nakagaki T, Ishibashi D, Taguchi Y, Mihara B, Iwasaki Y, Yoshida M, Nishida N.
  • Journal Title: Molecules. Volume: 24(24) Issue: 24 Pages: 4601-4601
  • DOI: 10.3390/molecules24244601
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Type I interferon protects neurons from prions in in vivo models (2019)
  • Author(s): Ishibashi Daisuke、Homma Takujiro、Nakagaki Takehiro、Fuse Takayuki、Sano Kazunori、Satoh Katsuya、Mori Tsuyoshi、Atarashi Ryuichiro、Nishida Noriyuki
  • Journal Title: Brain Volume: 142 Issue: 4 Pages: 1035-1050
  • DOI: 10.1093/brain/awz016
  • NAID: 120006987735
  • Peer Reviewed / Open Access
• [Journal Article] Crossed cerebellar diaschisis in Creutzfeldt-Jakob disease evaluated through single photon emission computed tomography. (2018)
  • Author(s): Nishioka K, Suzuki M, Satoh K, Hattori N.
  • Journal Title: J Neurol Sci Volume: 395 Pages: 88-90
  • DOI: 10.1016/j.jns.2018.09.027
  • Peer Reviewed
• [Journal Article] Proteomic approach to profiling immune complex antigens in cerebrospinal fluid samples from patients with central nervous system autoimmune diseases. (2018)
  • Author(s): Aibara N, Ichinose K, Baba M, Nakajima H, Satoh K, Atarashi R, Kishikawa N, Nishida N, Kawakami A, Kuroda N, Ohyama K
  • Journal Title: Clin Chim Acta Volume: 484 Pages: 26-31
  • DOI: 10.1016/j.cca.2018.05.026
  • Peer Reviewed
• [Journal Article] Creutzfeldt-Jakob disease with Alzheimer pathology, presenting with status epilepticus following repeated partial seizures: a case report and literature review. (2018)
  • Author(s): Miyake K, Hara T, Oshima E, Kawada K, Ishizu H, Yamauchi Y, Satoh K, Kitamoto T, Takenoshita S, Terada S, Yamada N
  • Journal Title: BMC Neurol. Volume: 18(1) Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12883-018-1055-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prion-Like Seeding of Misfolded α-Synuclein in the Brains of Dementia with Lewy Body Patients in RT-QUIC (2017)
  • Author(s): Sano Kazunori、Atarashi Ryuichiro、Satoh Katsuya、Ishibashi Daisuke、Nakagaki Takehiro、Iwasaki Yasushi、Yoshida Mari、Murayama Shigeo、Mishima Kenichi、Nishida Noriyuki
  • Journal Title: Molecular Neurobiology Volume: - Issue: 5 Pages: 3916-3930
  • DOI: 10.1007/s12035-017-0624-1
  • Peer Reviewed / Open Access
• [Journal Article] Clinical findings of a probable case of MM2-cortical-type sporadic Creutzfeldt-Jakob disease with antibodies to anti-N-terminus of α-enolase. (2017)
  • Author(s): Hayashi Y, Yamada M, Kimura A, Asano T, Satoh K, Kitamoto T, Yoneda M, Inuzuka T.
  • Journal Title: Prion. Volume: 11(6) Issue: 6 Pages: 454-464
  • DOI: 10.1080/19336896.2017.1377876
  • Peer Reviewed
• [Journal Article] An autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion assay. (2017)
  • Author(s): Hayashi Y, Iwasaki Y, Yoshikura N, Asano T, Mimuro M, Kimura A, Satoh K, Kitamoto T, Yoshida M, Inuzuka T.
  • Journal Title: Prion Volume: 11(4) Issue: 4 Pages: 284-292
  • DOI: 10.1080/19336896.2017.1345416
  • Peer Reviewed
• [Presentation] プリオン病の髄液診断 (2020)
  • Author(s): 佐藤克也
  • Organizer: 第６１回日本神経学会学術大会
• [Presentation] バイオマーカーとしてのαシヌクレイン (2020)
  • Author(s): 佐藤克也
  • Organizer: 第６１回日本神経学会学術大会
• [Presentation] アルツハイマー型認知症患者における食行動とグレリンとの関係 (2020)
  • Author(s): 佐藤克也
  • Organizer: 第39回日本認知症学会学術集会
• [Presentation] RT-QUIC法を応用したプリオン病患者のホルマリン固定能と病理ブロックからのプリオンシーリング活性の測定法の挑戦 (2019)
  • Author(s): 佐藤克也
  • Organizer: 第60回日本神経病理学会総会学術研究会
  • Invited
• [Presentation] Analysis for prion - seeding activity in formalin - fixed brains of human prion patients (2019)
  • Author(s): Trang Dong ,Yasushi Iwasaki, Masaki Takao, Mori Yoshida, Shigeo Murayama, Noriyuki Nishida, Katsuya Satoh
  • Organizer: APPS2019
  • Int'l Joint Research
• [Presentation] ヒトプリオン病患者におけるバイオマーカーの検討 (2019)
  • Author(s): 佐藤克也
  • Organizer: 第24回日本神経感染症学会総会・学術大会
  • Invited
• [Presentation] ヒトプリオン病患者におけるバイオマーカーの検討 (2019)
  • Author(s): 佐藤克也
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] Realtime quakinginduced conversion （RTQuIC）法を利用した認知症診断 (2019)
  • Author(s): 佐藤克也
  • Organizer: 第38回日本認知症学会学術集会
  • Invited
• [Presentation] 生体試料からの異常プリオンタンパクの検出による診断法開発 (2018)
  • Author(s): 佐藤克也、調漸、西田教行.
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] Eating behavior changed in the severity of dementia, and eating disturbance may contribute to the early admission into the facility through the observational study for two years. (2018)
  • Author(s): Satoh K, S Shirabe.
  • Organizer: th Congress of the European Academy of Neurology (EAN 2018).
  • Int'l Joint Research
• [Presentation] プリオン病における異常型プリオンタンパクの顧感度検出法の開発と神経変性疾患への応用. (2018)
  • Author(s): 佐藤克也
  • Organizer: 第91回日本生化学会大会
• [Presentation] 生体試料からの異常プリオンタンパクの検出による診断法開発 (2018)
  • Author(s): 佐藤克也
  • Organizer: 第23回日本神経感染症学会総会・学術大会
• [Presentation] Update on the utility of techniques for CSF biomarkers (2017)
  • Author(s): Katsuya Satoh
  • Organizer: Asia-Pacific Prion Symposium
  • Int'l Joint Research
• [Presentation] Biomarkers for human prion disease : Results from the Creutzfeldt-Jakob Disease Surveillance Committee in Japan (2017)
  • Author(s): Katsuya Satoh
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Book] 感染症疾患 15プリオン病 (2019)
  • Author(s): 佐藤克也
  • Publisher: 中山書店
  • ISBN: 9784521747491
• [Book] ウイルス検査法 臨床と検査室のための手引き (2018)
  • Author(s): 多屋 馨子、砂川 富正、西村 直子、佐藤 光、西村 秀一、寺田 喜平、相澤 悠太、齋藤 照彦、中山 哲夫、黒田 誠、白木 公康、皆川 洋子、細矢 光亮、駒瀬 勝啓、森 嘉生、木所 稔、尾崎 隆男、服部 文彦、吉川 哲史、要藤 裕孝、山田 雅夫、山下 信子、佐藤 克也
  • Total Pages: 392
  • Publisher: 春恒社
• [Book] Prion (2017)
  • Author(s): Katsuya SatohEmail authorRyuichiro AtarashiNoriyuki Nishida
  • Publisher: Springer
  • ISBN: 9781493972425
• [Patent(Industrial Property Rights)] プリオン病患者の毛根からプリオン活性の検出 (2021)
  • Inventor(s): 佐藤克也
  • Industrial Property Rights Holder: 佐藤克也
  • Industrial Property Rights Type: 特許
  • Filing Date: 2021