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Is Parkinson's disease lysosomal disease? A large-scale clinical and genetic approach

Research Project

Project/Area Number 19K17047
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionJuntendo University

Principal Investigator

Ogaki Kotaro  順天堂大学, 医学部, 非常勤講師 (20459035)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsパーキンソン病 / 遺伝子 / リソソーム病 / 神経科学 / 次世代シーケンサー / 脳神経内科 / 神経内科
Outline of Research at the Start

パーキンソン病(PD)の病態解明を目的とした原因遺伝子の同定は当該研究領域に飛躍的な進歩をもたらしたが、遺伝子スクリーニングでは陽性率は高々25%内外で未だ変異が決定されていない症例が殆どである。近年リソソーム病(Lysosomal storage disorders: LSD)の1つであるゴーシェ病を引き起こすGBA遺伝子がPDの最も重要なリスク感受性遺伝子の1つとして報告され、GBAの病態に沿ったプレシジョンメディスンの開発に繋がっている。申請者は家族性PDの大規模サンプルにて54のLSD原因遺伝子を網羅的に解析し、更なる新規PD関連遺伝子を単離し、PD病態解明を目指すことをゴールとする。

Outline of Final Research Achievements

At the discovery stage, 300 familial Parkinson's disease (PD) cases, 100 sporadic PD cases, and 200 healthy controls were used to comprehensively analyze 54 lysosomal disease (LSD) genes by targeted sequencing. From the obtained genetic information, we extracted genetic mutations in the familial PD patient group and the sporadic PD patient group, and added statistical analysis with the healthy control group and analysis using the genetic information of the public database. We narrowed down new candidates of causative genes and susceptibility genes. Next, we are going to add gene analyses of the replication stage and isolate novel PD-related genes.

Academic Significance and Societal Importance of the Research Achievements

新規原因遺伝子候補・感受性遺伝子単離後は、細胞実験・動物実験などの機能解析を進めリソソーム機能障害を治療ターゲットとした創薬を目指すのみならず、リソソーム病のような代謝性疾患ではenzyme replacement therapyが可能でありプレシジョンメディスンの開発を目指すことが可能である。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (37 results)

All 2022 2021 2020 2019

All Journal Article (22 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 22 results,  Open Access: 13 results) Presentation (10 results) Book (5 results)

  • [Journal Article] Evaluating the impact of adjunctive istradefylline on the cumulative dose of levodopa-containing medications in Parkinson’s disease: study protocol for the ISTRA ADJUST PD randomized, controlled study2022

    • Author(s)
      Hatano T、Kano O、Sengoku R、Yoritaka A、Suzuki K、Nishikawa N、Mukai Y、Nomura K、Yoshida N、Seki M、Matsukawa M K、Terashi H、Kimura K、Tashiro J、Hirano S、Murakami H、Joki H、Uchiyama T、Shimura H、Ogaki K、Fukae J、Tsuboi Y、Takahashi K、Yamamoto T、Yanagisawa N、Nagayama H
    • Journal Title

      BMC Neurology

      Volume: 22 Issue: 1 Pages: 71-71

    • DOI

      10.1186/s12883-022-02600-w

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson’s disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group study (CONST-PD)2022

    • Author(s)
      Taku Hatano, Genko Oyama, Yasushi Shimo, Kotaro Ogaki, Noriko Nishikawa, Jiro Fukae, Ryota Nakamura, Naohide Kurita, Taiji Tsunemi, Yutaka Oji, Shinji Saiki, Kenya Nishioka, Haruka Takeshige-Amano, et al.
    • Journal Title

      BMJ Open

      Volume: 12 Issue: 2 Pages: e054129-e054129

    • DOI

      10.1136/bmjopen-2021-054129

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An 88-year-old woman with acute disseminated encephalomyelitis following messenger ribonucleic acid-based COVID-19 vaccination2021

    • Author(s)
      Shimizu Mai、Ogaki Kotaro、Nakamura Ryota、Kado Eriko、Nakajima Sho、Kurita Naohide、Watanabe Masao、Yamashiro Kazuo、Hattori Nobutaka、Urabe Takao
    • Journal Title

      eNeurologicalSci

      Volume: 25 Pages: 100381-100381

    • DOI

      10.1016/j.ensci.2021.100381

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The East Asian Parkinson Disease Genomics Consortium2021

    • Author(s)
      Mok Kin Y、、、Funayama Manabu、、et al.
    • Journal Title

      The Lancet Neurology

      Volume: 20 Issue: 12 Pages: 982-982

    • DOI

      10.1016/s1474-4422(21)00373-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hashimoto's encephalopathy with gait disturbance caused by sensory ganglionopathy: A case report and review of the literature2021

    • Author(s)
      Shimada Tomoyo、Nakajima Sho、Nakamura Ryota、Kurita Naohide、Ogaki Kotaro、Watanabe Masao、Yamashiro Kazuo、Urabe Takao
    • Journal Title

      eNeurologicalSci

      Volume: 25 Pages: 100370-100370

    • DOI

      10.1016/j.ensci.2021.100370

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Commentary: Progressive Encephalomyelitis with Rigidity and Myoclonus and Myasthenia Gravis Comorbid Status with Thymoma2021

    • Author(s)
      Balint Bettina、Ogawa Takashi、Ogaki Kotaro、Daida Kensuke、Nishimaki Takayasu、Ando Maya、Kawajiri Sumihiro、Wada Ryo、Noda Kazuyuki、Hattori Nobutaka、Okuma Yasuyuki、Barsottini Orlando
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: 8 Issue: S1

    • DOI

      10.1002/mdc3.13303

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progressive Encephalomyelitis with Rigidity and Myoclonus and Myasthenia Gravis Comorbid Status with Thymoma2021

    • Author(s)
      Ogawa Takashi、Ogaki Kotaro、Daida Kensuke、Nishimaki Takayasu、Ando Maya、Kawajiri Sumihiro、Wada Ryo、Noda Kazuyuki、Hattori Nobutaka、Okuma Yasuyuki
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: 8 Issue: S1

    • DOI

      10.1002/mdc3.13293

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuronuclear and Neuromelanin‐Sensitive Imaging for Acquired Hepatocerebral Degeneration with Parkinsonism2021

    • Author(s)
      Ogawa Takashi、Ogaki Kotaro、Mori Yuko、Kamo Hikaru、Uchiyama Akira、Kamagata Koji、Nagaoka Masanori、Hattori Nobutaka
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: 8 Issue: 3 Pages: 464-468

    • DOI

      10.1002/mdc3.13166

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] プレシジョンメディスンの現状と展望, シンポジウム5: Parkinson 病の新規薬物療法:最新の動向と展望2021

    • Author(s)
      大垣光太郎, 服部信孝
    • Journal Title

      神経治療

      Volume: 38 Pages: 330-335

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK12021

    • Author(s)
      Hayashida Arisa、Li Yuanzhe、Yoshino Hiroyo、Daida Kensuke、Ikeda Aya、et al.
    • Journal Title

      Neurobiology of Aging

      Volume: 97 Pages: 3301-3301

    • DOI

      10.1016/j.neurobiolaging.2020.06.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parkinson’s disease: deep learning with a parameter-weighted structural connectome matrix for diagnosis and neural circuit disorder investigation2021

    • Author(s)
      Yasaka Koichiro、Kamagata Koji、Ogawa Takashi、Hatano Taku、Takeshige-Amano Haruka、Ogaki Kotaro、Andica Christina、Akai Hiroyuki、Kunimatsu Akira、Uchida Wataru、Hattori Nobutaka、Aoki Shigeki、Abe Osamu
    • Journal Title

      Neuroradiology

      Volume: Online ahead of print. Issue: 9 Pages: 1451-1462

    • DOI

      10.1007/s00234-021-02648-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Somnolence Preceded the Development of a Subthalamic Lesion in Neuromyelitis Optica Spectrum Disorder2020

    • Author(s)
      Daida Kensuke、Ogaki Kotaro、Hayashida Arisa、Ando Maya、Yokoyama Kazumasa、Noda Kazuyuki、Kanbayashi Takashi、Hattori Nobutaka、Okuma Yasuyuki
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 4 Pages: 577-579

    • DOI

      10.2169/internalmedicine.2947-19

    • NAID

      130007798428

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-02-15
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroimaging evaluation and successful treatment by using directional deep brain stimulation and levodopa in a patient with GNAO1-associated movement disorder: A case report2020

    • Author(s)
      Yamashita Yuri、Ogawa Takashi、Ogaki Kotaro、Kamo Hikaru、Sukigara Tomomi、Kitahara Eriko、Izawa Nana、Iwamuro Hirokazu、Oyama Genko、Kamagata Koji、Hatano Taku、Umemura Atsushi、Kosaki Rika、Kubota Masaya、Shimo Yasushi、Hattori Nobutaka
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 411 Pages: 116710-116710

    • DOI

      10.1016/j.jns.2020.116710

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advanced diffusion magnetic resonance imaging in patients with Alzheimer's and Parkinson's diseases2020

    • Author(s)
      Kamagata Koji、Andica Christina、Hatano Taku、Ogawa Takashi、Takeshige-Amano Haruka、Ogaki Kotaro、Akashi Toshiaki、Hagiwara Akifumi、Fujita Shohei、Aoki Shigeki
    • Journal Title

      Neural Regeneration Research

      Volume: 15 Issue: 9 Pages: 1590-1590

    • DOI

      10.4103/1673-5374.276326

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan2020

    • Author(s)
      Li Y、Ikeda A、Yoshino H、Oyama G、Kitani M、Daida K、Hayashida A、Ogaki K、Yoshida K、Kimura T、Nakayama Y、Ito H、Sugeno N、Aoki M、Miyajima H、Kimura K、Ueda N、Watanabe M、Urabe T、Takanashi M、Funayama M、Nishioka K、Hattori N
    • Journal Title

      Journal of Human Genetics

      Volume: ー Issue: 9 Pages: 771-781

    • DOI

      10.1038/s10038-020-0772-4

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mesial Frontal Lobe Infarction Presenting as Pisa Syndrome2020

    • Author(s)
      Noda Kazuyuki、Ando Maya、Jo Takayuki、Hattori Anri、Ogaki Kotaro、Sugiyama Mizuho、Hattori Nobutaka、Okuma Yasuyuki
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 29 Issue: 8 Pages: 104882-104882

    • DOI

      10.1016/j.jstrokecerebrovasdis.2020.104882

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel GFAP p.Glu206Ala Mutation in Alexander Disease with Decreased Dopamine Transporter Uptake2020

    • Author(s)
      Ogawa Takashi、Ogaki Kotaro、Ishiguro Mayu、Ando Maya、Yoshida Tomokatsu、Noda Kazuyuki、Hattori Nobutaka、Okuma Yasuyuki
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: 7 Issue: 6 Pages: 720-722

    • DOI

      10.1002/mdc3.12998

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Disease-Associated Variants by Targeted Gene Panel Resequencing in Parkinson's Disease2020

    • Author(s)
      Daida Kensuke、Funayama Manabu、Li Yuanzhe、Yoshino Hiroyo、Hayashida Arisa、Ikeda Aya、Ogaki Kotaro、Nishioka Kenya、Hattori Nobutaka
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 576465-576465

    • DOI

      10.3389/fneur.2020.576465

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brain White-Matter Degeneration Due to Aging and Parkinson Disease as Revealed by Double Diffusion Encoding2020

    • Author(s)
      Kamiya Kouhei、Kamagata Koji、Ogaki Kotaro、Hatano Taku、Ogawa Takashi、Takeshige-Amano Haruka、Murata Syo、Andica Christina、Murata Katsutoshi、Feiweier Thorsten、Hori Masaaki、Hattori Nobutaka、Aoki Shigeki
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 584-510

    • DOI

      10.3389/fnins.2020.584510

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel GFAP p. Glu206Ala mutation in Alexander disease with decreased dopamine transporter uptake2020

    • Author(s)
      Takashi Ogawa, Kotaro Ogaki, Mayu Ishiguro, Maya And, Tomokatsu Yoshida, Kazuyuki Noda, Nobutaka Hattori, Yasuyuki Okuma. Novel GFAP p. Glu206Ala mutation in Alexander disease with decreased dopamine transporter uptake.
    • Journal Title

      Movement Disorders Clinical Practice

      Volume: ー

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MR biomarkers of degenerative brain disorders derived from diffusion imaging2019

    • Author(s)
      Andica Christina、Kamagata Koji、Hatano Taku、Saito Yuya、Ogaki Kotaro、Hattori Nobutaka、Aoki Shigeki
    • Journal Title

      Journal of Magnetic Resonance Imaging

      Volume: ー Issue: 6 Pages: 1620-1636

    • DOI

      10.1002/jmri.27019

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bilateral thigh compartment syndromes from extended sitting with forward bending.2019

    • Author(s)
      Shimada T, Tsunemi T, Hattori A, Nakazato-Taniguchi T, Yasuhara H, Ogaki K, Hattori N
    • Journal Title

      J Clin Neurosci

      Volume: 5868 Pages: 30213-9

    • DOI

      10.1016/j.jocn.2019.03.027

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Detection of genetic modifiers in PRKN,2021

    • Author(s)
      Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashid, a, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori.
    • Organizer
      第14回パーキンソン病・運動障害疾患コングレス 福岡
    • Related Report
      2021 Research-status Report
  • [Presentation] Searching for genetic modifiers of PRKN2021

    • Author(s)
      Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashid, a, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori.
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Detection of genetic modifiers in PRKN2021

    • Author(s)
      大垣光太郎、中岡博史、代田健祐、林田有紗、池田彩、李元哲、吉野浩代、舩山学、西岡健弥、井ノ上 逸朗、服部信孝
    • Organizer
      第14回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2020 Research-status Report
  • [Presentation] プレシジョンメディシスンに遺伝子診断は必要か2020

    • Author(s)
      大垣光太郎 服部信孝
    • Organizer
      高松国際パーキンソン病シンポジウム 2020
    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Presentation] Searching for genetic modifiers in PRKN2020

    • Author(s)
      Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashida, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] プレシジョンメティスンの現状と展望2020

    • Author(s)
      大垣光太郎 服部信孝
    • Organizer
      第38回日本神経治療学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Detection of genetic modifiers in parkin2019

    • Author(s)
      Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashida, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genetic analyses of HTRA1 and CTSA in Japanese patients with cerebral small vessel disease2019

    • Author(s)
      Hikaru Kamo, Silvio A. Conedera, Kotaro Ogaki, Kensuke Daida, Yuanzhe Li, Masuo Funabashi, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Nobutaka Hattori
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Genotype-phenotype correlation of LRP10 mutations among familial Parkinson's disease2019

    • Author(s)
      Kensuke Daida, Yuanzhe Li, Manabu Funayama, Kotaro Ogaki, Hiroyo Yoshino, Akio Kikuchi, Fumitaka Hasegawa, Kenya Nishioka, Nobutaka Hattori
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] nalysis of intronic region of PRKN in PD with heterozygous PRKN mutation.2019

    • Author(s)
      大垣光太郎、中岡博史、代田健祐、林田有紗、池田彩、李元哲、吉野浩代、舩山学、西岡健弥、井ノ上 逸朗、服部信孝
    • Organizer
      第13回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2019 Research-status Report
  • [Book] 遺伝性パーキンソン病の研究から目指す治療法開発, 順天堂大脳神経内科ではこうしている 最新 パーキンソン病診療【電子版付】2021

    • Author(s)
      大垣光太郎
    • Total Pages
      224
    • Publisher
      日本医事新報社
    • ISBN
      9784784949502
    • Related Report
      2021 Research-status Report
  • [Book] 遅発性ジスキネジア[私の治療]週刊日本医事新報 5010号2020

    • Author(s)
      大垣光太郎 服部信孝
    • Total Pages
      1
    • Publisher
      日本医事新報
    • Related Report
      2020 Research-status Report
  • [Book] 遅発性ジスキネジア[私の治療]2020

    • Author(s)
      大垣光太郎, 服部信孝
    • Total Pages
      2
    • Publisher
      日本医事新報社
    • Related Report
      2019 Research-status Report
  • [Book] Parkinson病及び関連疾患の治療の進歩 2018. 神経治療36: 1-4, 20192019

    • Author(s)
      大垣光太郎, 服部信孝
    • Total Pages
      4
    • Publisher
      日本神経治療学会
    • Related Report
      2019 Research-status Report
  • [Book] パーキンソン病. 希少疾病ライブラリ2019

    • Author(s)
      大垣光太郎, 服部信孝
    • Total Pages
      10
    • Publisher
      株式会社ケアネット
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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