Establishments of diagnosis for patients' CSF in humanprion disease and novel prion clinical research through field work

• Project/Area Number: 26305030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• 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)
• Co-Investigator(Kenkyū-buntansha): 森 剛志 長崎大学, 医歯薬学総合研究科(医学系), 助教 (40426565) ; 新 竜一郎 宮崎大学, 医学部, 教授 (90452846)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: プリオン病 / 診断法 / 臨床症状 / 髄液検査 / クロイツフェルト・ヤコブ病 / ゲルストマン・ストロイスラー・シャインカー病 / 髄液 / クロイツフェルト・ヤコプ病(CJD)

Outline of Final Research Achievements

We succeeded in detecting the ultra-small amount of abnormal prion protein in patients’ CSF with prion disease for the first time in the world. Furthermore, drugs with potential for treatment of prion diseases have been reported, and interventional intervention trials have been initiated. We research for therapeutic research and research for the early diagnosis of prion diseases· Establishment of pathology markers of prion diseases for research purpose. We also try to diagnose prion diseases from peripheral blood.
On the other hand, we will perform the global research group of rapid progressive dementia research, and as a top runner in the research of spinal fluid cerebrospinal fluid, we will conduct joint research on clinical application of biomarker and abnormal prion protein. Furthermore, although it is rare in Japan, we will try to explore pathogenic makers of clinical trials of fatal familial insomnia that has been reported abroad.

Research Products

• [Int'l Joint Research] ゲッチン大学(ドイツ)
• [Int'l Joint Research] メルボルン大学(オーストラリア)
• [Int'l Joint Research] ハーリム大学(韓国)
• [Int'l Joint Research] エジンバラ大学(英国)
• [Int'l Joint Research] ゲッチンゲン大学(ドイツ)
• [Int'l Joint Research] メルボルン大学(オーストラリア)
• [Int'l Joint Research] ロンドン大学/エジンバラ大学(英国)
• [Int'l Joint Research] Hallym 大学(韓国)
• [Int'l Joint Research] Instituto de Salud Carlos II/Hospital Clinic,IDIBAPS, Barcelona(スペイン)
• [Int'l Joint Research]
• [Journal Article] プリオン病の診断 (2017)
  • Author(s): 佐藤 克也
  • Journal Title: Pharma Medica Volume: 35(2) Pages: 47-53
• [Journal Article] An autopsy-verified case of FTLD-TDP type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. (2016)
  • Author(s): Hayashi Y, Iwasaki Y, Takekoshi A, Yoshikura N, Asano T, Mimuro M, Kimura A, Satoh K, Kitamoto T, Yoshida M, Inuzuka T.
  • Journal Title: Prion. Volume: 10(6) Issue: 6 Pages: 492-501
  • DOI: 10.1080/19336896.2016.1243192
  • Peer Reviewed
• [Journal Article] Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients. (2016)
  • Author(s): Takatsuki H, Fuse T, Nakagaki T, Mori T, Mihara B, Takao M, Iwasaki Y, Yoshida M, Murayama S, Atarashi R, Nishida N, Satoh K.
  • Journal Title: EBioMedicine Volume: 12 Pages: 150-155
  • NAID: 120006987618
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preserved regional cerebral blood flow in the occipital cortices, brainstem, and cerebellum of patients with V180I-129M genetic Creutzfeldt-Jakob disease in serial SPECT studies. (2016)
  • Author(s): Hayashi Y, Yoshikura N, Takekoshi A, Yamada M, Asano T, Kimura A, Satoh K, Kitamoto T, Inuzuka T.
  • Journal Title: J Neurol Sci. Volume: 370 Pages: 145-151
  • DOI: 10.1016/j.jns.2016.09.043
  • Peer Reviewed
• [Journal Article] The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. (2016)
  • Author(s): Schmitz M, Cramm M, Llorens F, Muller-Cramm D, Collins S, Atarashi R, Satoh K, Orru CD, Groveman BR, Zafar S, Schulz-Schaeffer WJ, Caughey B, Zerr I.
  • Journal Title: Nat Protoc. Volume: 11 Issue: 11 Pages: 2233-2242
  • DOI: 10.1038/nprot.2016.120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sequential Washing with Electrolyzed Alkaline and Acidic Water Effectively Removes Pathogens from Metal Surfaces. (2016)
  • Author(s): Nakano Y, Akamatsu N, Mori T, Sano K, Satoh K, Nagayasu T, Miyoshi Y, Sugio T, Sakai H, Sakae E, Ichimiya K, Hamada M, Nakayama T, Fujita Y, Yanagihara K, Nishida N. Sequential
  • Journal Title: PLoS One Volume: 11(5) Issue: 5 Pages: e0156058-e0156058
  • DOI: 10.1371/journal.pone.0156058
  • Peer Reviewed / Open Access
• [Journal Article] CSF RT-QuIC is a robust and reliable test for sporadic CJD: An international study. (2016)
  • Author(s): McGuire LI, Poleggi A, Poggiolini I, Suardi S, Grznarova K, Shi S, de Vil B, Sarros S, Satoh K, Cheng K, Cramm M, Fairfoul G, Schmitz M, Zerr I, Cras P, Equestre M, Tagliavini F, Atarashi R, Knox D, Collins S, Haik S, Parchi P, Pocchiari M, Green A.
  • Journal Title: Ann Neurol. Volume: 未定 Issue: 1 Pages: 160-165
  • DOI: 10.1002/ana.24679
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A direct assessment of human prion adhered to steel wire using real-time quaking-induced conversion. (2016)
  • Author(s): Mori T, Atarashi R, Furukawa K, Takatsuki H, Satoh K, Sano K, Nakagaki T, Ishibashi D, Ichimiya K, Hamada M, Nakayama T, Nishida N.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 24993-24993
  • DOI: 10.1038/srep24993
  • Peer Reviewed / Open Access
• [Journal Article] プリオン病の脳脊髄液検査 (2016)
  • Author(s): 佐藤 克也, 新 竜一郎, 西田 教行
  • Journal Title: 神経内科 Volume: 84(3) Pages: 254-259
• [Journal Article] Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt-Jakob Disease Diagnostic. (2016)
  • Author(s): Schmitz M, Ebert E, Stoeck K, Karch A, Collins S, Calero M, Sklaviadis T, Laplanche JL, Golanska E, Baldeiras I, Satoh K, Sanchez-Valle R, Ladogana A, Skinningsrud A, Hammarin AL, Mitrova E, Llorens F, Kim YS, Green A, Zerr I.
  • Journal Title: Mol Neurobiol Volume: 53(4) Issue: 4 Pages: 2189-99
  • DOI: 10.1007/s12035-015-9167-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. (2016)
  • Author(s): Cramm M, Schmitz M, Karch A, Mitrova E, Kuhn F, Schroeder B, Raeber A, Varges D, Kim YS, Satoh K, Collins S, Zerr I.
  • Journal Title: Mol Neurobiol Volume: 53(3) Issue: 3 Pages: 1896-904
  • DOI: 10.1007/s12035-015-9133-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of (99m)Tc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. (2015)
  • Author(s): Hayashi Y, Iwasaki Y, Yoshikura N, Asano T, Hatano T, Tatsumi S, Satoh K, Kimura A, Kitamoto T, Yoshida M, Inuzuka T.
  • Journal Title: J Neurol Sci Volume: 358 Issue: 1-2 Pages: 447-452
  • DOI: 10.1016/j.jns.2015.09.356
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases. (2015)
  • Author(s): Takatsuki H, Satoh K, Sano K, Fuse T, Nakagaki T, Mori T, Ishibashi D, Mihara B, Takao M, Iwasaki Y, Yoshida M, Atarashi R, Nishida N.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: 0126930-0126930
  • DOI: 10.1371/journal.pone.0126930
  • NAID: 120006986998
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ubiquitin-specific protease 14 modulates degradation of cellular prion protein. (2015)
  • Author(s): Homma T, Ishibashi D, Nakagaki T, Fuse T, Mori T, Satoh K, Atarashi R, Nishida N.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 11028-11028
  • DOI: 10.1038/srep11028
  • Peer Reviewed / Open Access
• [Journal Article] Creutzfeldt-Jakob Disease with a prion protein gene codon 180 mutation presenting asymmetric cortical high-intensity on magnetic resonance imaging. (2015)
  • Author(s): Amano Y, Kimura N, Hanaoka T, Aso Y, Hirano T, Murai H, Satoh K, Matsubara E.
  • Journal Title: Prion. Volume: 9(1) Issue: 1 Pages: 29-33
  • DOI: 10.1080/19336896.2015.1017703
  • Peer Reviewed / Open Access
• [Journal Article] Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. (2015)
  • Author(s): Cramm M, Schmitz M, Karch A, Mitrova E, Kuhn F, Schroeder B, Raeber A, Varges D, Kim YS, Satoh K, Collins S, Zerr I.
  • Journal Title: Mol Neurobiol Volume: 51
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3. (2014)
  • Author(s): Homma T, Ishibashi D, Nakagaki T, Fuse T, Sano K, Satoh K, Atarashi R, Nishida N.
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 6006-6006
  • DOI: 10.1038/srep06006
  • NAID: 120006986450
  • Peer Reviewed / Open Access
• [Journal Article] Conformational properties of prion strains can be transmitted to recombinant prion protein fibrils in real-time quaking-induced conversion. (2014)
  • Author(s): Sano K, Atarashi R, Ishibashi D, Nakagaki T, Satoh K, Nishida N.
  • Journal Title: J Virol Volume: 88(20) Issue: 20 Pages: 11791-11801
  • DOI: 10.1128/jvi.00585-14
  • NAID: 120006986372
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene. (2014)
  • Author(s): Qina, T., N. Sanjo, M. Hizume, M. Higuma, M. Tomita, R. Atarashi, K. Satoh, I. Nozaki, T. Hamaguchi, Y. Nakamura, A. Kobayashi, T. Kitamoto, S. Murayama, H. Murai, M. Yamada and H. Mizusawa
  • Journal Title: BMJ Open Volume: 4 Issue: 5 Pages: e004968-e004968
  • DOI: 10.1136/bmjopen-2014-004968
  • NAID: 120006986552
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of p62/SQSTM1 in prion diseases and its association with (2014)
  • Author(s): Homma T, Ishibashi D, Nakagaki T, Satoh K, Sano K, Atarashi R, Nishida N.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 4504-4504
  • DOI: 10.1038/srep04504
  • Peer Reviewed / Open Access
• [Presentation] 本邦のCJDサーベイランスにおけるプリオン病の脳波診断 (2016)
  • Author(s): 3.黒岩 義之, 太組 一朗, 村井 弘之, 春日 健作, 中村 好一, 藤野 公裕, 黒川 隆史, 馬場 泰尚, 佐藤 克也, 原田 雅史, 北本 哲之, 塚本 忠, 山田 正仁, 水澤 英洋
  • Organizer: 第46回日本臨床神経生理学会学術大会
  • Place of Presentation: ホテルハマツ(福島県・郡山市）
  • Year and Date: 2016-10-27
  • Invited
• [Presentation] 異常型プリオンタンパク試験管内増幅法(RT-QUIC法)によるプリオン病患者の生体材料(髄液・各臓器)での定量系確立 (2016)
  • Author(s): 佐藤 克也, 調 漸, 布施 隆行, 西田 教行
  • Organizer: 日本神経感染症学会学術集会
  • Place of Presentation: ANAクラウンプラザホテル金沢(石川県・金沢市）
  • Year and Date: 2016-10-17
• [Presentation] HTLV-1関連脊髄症に随伴する神経因性過活動膀胱に対するプロスルチアミン経口薬の効果. (2016)
  • Author(s): 松尾 朋博, 佐藤 克也, 中村 龍文, 宮田 康好, 酒井 英樹
  • Organizer: 日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2016-09-29
• [Presentation] プリオン病における免疫反応 (2016)
  • Author(s): 佐藤 克也
  • Organizer: 日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] 脳ドックで発見されたクロイツフェルト・ヤコブ病の1例 (2016)
  • Author(s): 佐藤 克也,
  • Organizer: 日本早期認知症学会学術集会
  • Place of Presentation: 熊本県交流間パレア鶴屋ホール(熊本県熊本市）
  • Year and Date: 2016-09-27
• [Presentation] ：日本におけるプリオン病患者のバイオマーカーの有効性に関する前向き研究. (2016)
  • Author(s): 佐藤 克也, 西田 教行, 調 漸
  • Organizer: 日本神経学会学術集会
  • Place of Presentation: 神戸コンベンションセンター・神戸ポートピアホテル (兵庫県・神戸市）
  • Year and Date: 2016-05-20
• [Presentation] MM2皮質型孤発性Creutzfeldt-Jakob病の臨床診断 (2015)
  • Author(s): 浜口 毅(金沢大学 大学院脳老化・神経病態学(神経内科)), 三條 伸夫, 中村 好一, 村山 繁雄, 佐藤 克也, 原田 雅史, 水澤 英洋, 山田 正仁, CJDサーベイランス委員会
  • Organizer: 日本認知症学会
  • Place of Presentation: リンクステーションホール青森（青森県）
  • Year and Date: 2015-10-02
• [Presentation] MM2型孤発性Creutzfeldt-Jakob病の臨床的特徴と診断基準案の提案 (2015)
  • Author(s): 浜口 毅(金沢大学 大学院脳老化・神経病態学(神経内科)), 坂井 健二, 野崎 一朗, 篠原 もえ子, 三條 伸夫, 中村 好一, 北本 哲之, 村山 繁雄, 佐藤 克也, 原田 雅史, 水澤 英洋, 山田 正仁
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ (新潟コンベンションセンター)（新潟県）
  • Year and Date: 2015-05-20
• [Presentation] Analysis of biomarkers and RT-QUIC method of CSF in prion disease’ patients (2015)
  • Author(s): Katsuya Satoh，Ryuichiro Atarashi，Hanae Takatuki，Tsuyoshi Mori，
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ (新潟コンベンションセンター)（新潟県）
  • Year and Date: 2015-05-20
  • Int'l Joint Research
• [Presentation] CSF analysis of patients with human prion disease (2014)
  • Author(s): Satoh K
  • Organizer: Asian Pacific Prion Symposium 2014
  • Place of Presentation: 韓国、チェジュ島
  • Year and Date: 2014-07-06 – 2014-07-07
• [Remarks] プリオン病の髄液検査
  • URL: http://www.am.nagasaki-u.ac.jp/rehabilitation/prion/
• [Remarks] プリオン病のサーベイランスと感染予防に関する調査研究班 研究成果
  • URL: http://mos-jp.com/prion/survey/index.html
• [Remarks] プリオン病及び遅発性ウイルス感染症に関する調査研究班
  • URL: http://mos-jp.com/prion/virus/index.html