Study of physiological back ground of motor axonal ion channel dysfunction in amyotrophic lateral sclerosis

• Project/Area Number: 26461319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Kanai Kazuaki 順天堂大学, 医学部, 准教授 (10375751)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 筋萎縮性側索硬化症 / チャネロパチー / 神経軸索興奮特性 / ナトリウムチャンネル / 神経変性 / 後天性チャネロパチー / 神経過剰興奮性 / ナトリウムチャネル / RNA代謝障害 / 神経保護

Outline of Final Research Achievements

We performed the nerve excitability measurements in patients with amyotrophic lateral sclerosis. We confirmed that changes in some indices of nerve excitability measurements such as strength-duration time constant (SDTC) or early component of depolarizing threshold electrotonus (TEd10-30) were strong indicators of prognosis of patients with amyotrophic lateral sclerosis. We found changes in SDTC and TEd10-30 were associated with those in the already known prognostic factors. We performed the measurements of miRNA in patients with amyotrophic lateral sclerosis. We compared the results of nerve excitability measurements and of miRNA in patients with amyotrophic lateral sclerosis.

Research Products

• [Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy. (2018)
  • Author(s): Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
  • Journal Title: J Neural Transm (Vienna) Volume: - Issue: 6 Pages: 938-944
  • DOI: 10.1007/s00702-018-1885-1
  • Peer Reviewed / Open Access
• [Journal Article] Isaacs syndrome: A slow potassium channelopathy caused by autoantibodies? (2018)
  • Author(s): Nakazato T, Tsuji Y, Kanai K, Noto YI, Hoshino Y, Yamashiro K, Yokoyama K, Nishioka K, Shimo Y, Watanabe O, Mizuno T, Hattori N.
  • Journal Title: Clin Neurophysiol. Volume: 129 Issue: 5 Pages: 956-958
  • DOI: 10.1016/j.clinph.2018.01.069
  • Peer Reviewed
• [Journal Article] Parkinsonism in a patient with valosin-containing protein gene mutation showing: a case report. (2017)
  • Author(s): Fujimaki M, Kanai K, Funabe S, Takanashi M, Yokoyama K, Li Y, Hattori N.
  • Journal Title: J Neurol Volume: 264 Issue: 6 Pages: 1284-1286
  • DOI: 10.1007/s00415-017-8467-2
  • Peer Reviewed / Open Access
• [Journal Article] Paraneoplastic neuromyotonia due to lung carcinoma and invisible muscle cramps evaluated using ultrasonography. (2017)
  • Author(s): Nishioka K, Kanai K, Hattori N.
  • Journal Title: J Neurooncol. Volume: 134 Issue: 1 Pages: 243-244
  • DOI: 10.1007/s11060-017-2501-1
  • Peer Reviewed
• [Journal Article] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort (2016)
  • Author(s): Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
  • Journal Title: Neurobiology of Aging Volume: 39 Pages: 219-219
  • DOI: 10.1016/j.neurobiolaging.2015.11.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Utility of ultrasonography in evaluating muscle contractions in stiff-person syndrome. (2016)
  • Author(s): Hoshino Y, Nishioka K, Kanai K, Tanaka R, Nagaoka M, Kuwabara S, Hattori N.
  • Journal Title: J Neurol Sci. Volume: 367 Pages: 361-2
  • DOI: 10.1016/j.jns.2016.06.044
  • Peer Reviewed
• [Journal Article] A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. (2016)
  • Author(s): Watanabe H, Atsuta N, Hirakawa A, Nakamura R, Nakatochi M, Ishigaki S, Iida A, Sobue G.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: in press Issue: 8 Pages: 851-8
  • DOI: 10.1136/jnnp-2015-311541
  • Peer Reviewed
• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy (2015)
  • Author(s): Mitsui J, Matsukawa T, Sasaki H, Yabe I, Nakahara Y, Momose Y, Takahashi Y, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Tsuji S, et al.
  • Journal Title: Ann Clin Transl Neurol. Volume: 2 Issue: 4 Pages: 417
  • DOI: 10.1002/acn3.185
  • URL: https://localhost/en/publications/c946bad2-a238-4d0e-a396-6d33b3922ab7
  • Peer Reviewed / Open Access
• [Journal Article] A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan. (2014)
  • Author(s): Yasui K, Yabe I, Yoshida K, Kanai K, Arai K, Ito M, Onodera O, Koyano S, Isozaki E, Sawai S, Adachi Y, Sasaki H, Kuwabara S, Hattori T, Sobue G, Mizusawa H, Tsuji S, Nishizawa M, Nakashima K.
  • Journal Title: Orphanet Jounal of Rare Diseases Volume: 9 Issue: 1 Pages: 118-118
  • DOI: 10.1186/s13023-014-0118-4
  • Peer Reviewed / Open Access
• [Presentation] Increased motor axonal persistent sodium currents is associated with rapid regional spreading in amyotrophic lateral sclerosis (2017)
  • Author(s): Kazuaki Kanai, Takanori Yokota, Kazumoto Shibuya, Tadashi Kanouchi, Tomoko Nakazato, Yuta Iwai, Sonoko Misawa, Genko Oyama, Yasushi Shimo, Michitaka Mikasa, Motoki Fujimaki, Yasuhiro Kagamihara, Toshio Shimizu, Nobutaka Hattori, Satoshi Kuwabra
  • Organizer: The XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Greater axonal persistent sodium currents correlate with more rapid disease progression in patients with amyotrophic lateral sclerosis (2017)
  • Author(s): Tomoko Nakazato, Kazuaki Kanai, Genkyo Oyama, Yasushi Shimo, Nobutaka Hattori.
  • Organizer: The XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Increased Barrett-Barrett conductance in motor axons of patients with anti-GAD antibody (2017)
  • Author(s): T Nakazato, K Kanai, Y Shimo, H Bostock, N Hattori
  • Organizer: The 16th European Congress of Clinical Neurophysiology
  • Int'l Joint Research
• [Presentation] 抗MAG抗体陽性ニューロパチーの運動神経軸索興奮特性 (2017)
  • Author(s): 金井 数明、中里 朋子、下 泰司、大山 彦光、服部信孝
  • Organizer: 第47回日本臨床神経生理学会
• [Presentation] 抗GAD抗体は運動神経軸索のBarrett-Barrett conductanceを増大させる (2017)
  • Author(s): 中里 朋子、金井 数明、西岡 健弥、大山 彦光、下 泰司、服部 信孝
  • Organizer: 第47回日本臨床神経生理学会
• [Presentation] 遺伝性神経疾患における自律神経機能障害 (2016)
  • Author(s): 金井 数明 服部 信孝
  • Organizer: 第69回日本自律神経学会総会
  • Place of Presentation: 熊本 県民交流館パレアホール・熊本県・熊本市
  • Year and Date: 2016-11-10
  • Invited
• [Presentation] タウオパチーにおける感覚神経の軸索興奮特性 (2016)
  • Author(s): 金井 数明、中里朋子、藤巻基紀、中谷光良、大山彦光、下 泰司、服部 信孝
  • Organizer: 第46回日本臨床神経生理学会総会
  • Place of Presentation: ホテルハマツ・福島県・郡山市
  • Year and Date: 2016-10-27
• [Presentation] 抗VGKC 抗体陰性／抗CRMP-5 抗体陽性Isaacs 症候群患者における運動神経軸索K+チャネル機能障害 (2016)
  • Author(s): 中里 朋子、金井 数明、西岡 健弥、藤巻 基紀、大山 彦光、下 泰司、横山 和正、服部 信孝
  • Organizer: 第46回日本臨床神経生理学会総会
  • Place of Presentation: ホテルハマツ・福島県・郡山市
  • Year and Date: 2016-10-27
• [Presentation] CHCHD2遺伝子変異が運動神経軸索膜特性に与える影響 (2016)
  • Author(s): 金井数明， 中里朋子， 藤巻基樹， 西岡健弥， 服部信考
  • Organizer: 第57回日本神経学会総会
  • Place of Presentation: 神戸コンベンションセンター・兵庫県・神戸市
  • Year and Date: 2016-05-18
• [Presentation] 抗GAD抗体陽性患者において運動神経軸索のfast K+チャネルは抑制される (2016)
  • Author(s): T Nakazato, K Kanai, K Nishioka, M Fujimaki, G Oyama, Y Shimo, N Hattori
  • Organizer: 第57回日本神経学会総会
  • Place of Presentation: 神戸コンベンションセンター・兵庫県・神戸市
  • Year and Date: 2016-05-18
• [Presentation] 筋萎縮性側索硬化症における感覚神経の軸索興奮特性 (2015)
  • Author(s): 金井 数明，中里 朋子，藤巻 基紀，中谷 光良，大山 彦光，下 泰司，服部 信孝
  • Organizer: 第45回日本臨床神経生理学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-05
• [Presentation] 筋萎縮性側索硬化症におけるK+電流の発症から診断までの期間に対する影響の検討 (2015)
  • Author(s): 中里 朋子，金井 数明，藤巻 基紀，大山 彦光，下 泰司，服部 信孝
  • Organizer: 第45回日本臨床神経生理学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-05
• [Presentation] 多発性硬化症における末梢神経病変：神経伝導速度検査と軸索興奮性検査による検討 (2015)
  • Author(s): 藤巻 基紀，金井 数明，中里 朋子，横山 和正，服部 信孝
  • Organizer: 第45回日本臨床神経生理学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-05
• [Presentation] 持続性Na＋電流は筋萎縮性側索硬化症の予後に関与する (2015)
  • Author(s): 中里 朋子、金井 数明、藤巻 基紀、大山 彦光、下 泰司、服部 信孝
  • Organizer: 第56回日本神経学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20 – 2015-05-23
• [Presentation] 多発性硬化症における神経伝導検査と軸索興奮特性検査による末梢神経病変の検討 (2015)
  • Author(s): 藤巻 基紀、中里 朋子、金井 数明、横山 和正、服部 信孝
  • Organizer: 第56回日本神経学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20 – 2015-05-23
• [Presentation] 持続性Na+電流は筋萎縮性側索硬化症の予後に関与する (2015)
  • Author(s): 中里 朋子，金井 数明，藤巻 基紀，大山 彦光，下 泰司，服部 信孝
  • Organizer: 第56回日本神経学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] 多発性硬化症における神経伝導検査と神経軸索興奮特性検査による末梢神経病変の検討 (2015)
  • Author(s): 藤巻 基紀，中里 朋子，金井 数明，横山 和正，服部 信孝
  • Organizer: 第56回日本神経学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] 神経軸索興奮性検査における刺激装置条件の検討 (2014)
  • Author(s): 金井 数明、中里 朋子、藤巻 基紀、桑原 聡、服部 信孝
  • Organizer: 第44回日本臨床神経生理学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-19 – 2014-11-21