Ion channel dysfunction and small molecule homeostasis dysregulation in amyotrophic lateral sclerosis

• Project/Area Number: 17K09811
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Fukushima Medical University (2018-2019); Juntendo University (2017)
• Principal Investigator: Kanai Kazuaki 福島県立医科大学, 医学部, 教授 (10375751)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 筋萎縮性側索硬化症 / 軸索興奮特性 / 後天性チャネロパチー / 神経過剰興奮性 / 神経内科学 / チャネロパチー

Outline of Final Research Achievements

In patients with amyotrophic lateral sclerosis, we investigated the association between motor axonal excitability abnormality and small molecule expression dysregulation in biological fluids. We divided the patients into two groups (a high value group and a low value group) on the basis of neurophysiological indices that are associated with prognosis. As results, we found several small molecules that were correlated with neurophysiological indices that are associated with prognosis.

Academic Significance and Societal Importance of the Research Achievements

これまでもALSにおける有力な病態仮説であったグルタミン酸興奮毒性仮説を説明し得る結果が得られた。またALSにおける新規治療法開発における有力なサロゲートマーカーとなる可能性が示唆され、今後の治療法開発に役立つ可能性が示された。

Research Products

• [Journal Article] Prognosis of amyotrophic lateral sclerosis patients undergoing tracheostomy invasive ventilation therapy in Japan (2020)
  • Author(s): Hayashi Naoki、Atsuta Naoki、Yokoi Daichi、Nakamura Ryoichi、Nakatochi Masahiro、Katsuno Masahisa、Izumi Yuishin、Kanai Kazuaki、Hattori Nobutaka、Taniguchi Akira、Morita Mitsuya、Kano Osamu、Shibuya Kazumoto、Kuwabara Satoshi、Suzuki Naoki、Aoki Masashi、Aiba Ikuko、Mizoguchi Kouichi、Oda Masaya、Kaji Ryuji、Sobue Gen
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 91 Issue: 3 Pages: 285-290
  • DOI: 10.1136/jnnp-2019-322213
  • Peer Reviewed / Open Access
• [Journal Article] Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone. (2019)
  • Author(s): J. S. Lee, K. Kanai, M. Suzuki, W. S. Kim, H. S. Yoo, Y. Fu, D-K. Kim, B. C. Jung, M. Choi, K. W. Oh, Y. Li, M. Nakatani, T. Nakazato, S. Sekimoto, M. Furuyama, H. Yoshino, S. Kubo, K. Nishioka, R. Sakai, M. Ueyama, H. Mochizuki, H-J. Lee, S. P. Sardi, G. M. Halliday, Y. Nagai, P. H. Lee, N. Hattori, S-J. Lee
  • Journal Title: Brain Volume: 142 Issue: 9 Pages: 2845-59
  • DOI: 10.1093/brain/awz205
  • Peer Reviewed / Int'l Joint Research
• [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] The Japanese early-stage trial of high-dose methylcobalamin for amyotrophic lateral sclerosis (JETALS): Protocol for a randomized controlled trial (2018)
  • Author(s): Oki Ryosuke、Izumi Yuishin、Nodera Hiroyuki、Ishihara Tomohiko，Kaji Ryuji、JETALS et al.
  • Journal Title: JMIR Research Protocols Volume: 7 Issue: 12 Pages: e12046-e12046
  • DOI: 10.2196/12046
  • Peer Reviewed / Open Access
• [Journal Article] Myalgia caused by chronic myositis associated with plasmacytosis: a case report. (2018)
  • Author(s): Hatano T, Takanashi M, Tsuchihashi H, Ueno SI, Hayashida A, Tsukune Y, Kanai K, Shimo Y, Hattori N.
  • Journal Title: BMC Neurol. Volume: 18 Issue: 1 Pages: 112-112
  • DOI: 10.1186/s12883-018-1123-3
  • Peer Reviewed / Open Access
• [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
• [Presentation] 閾値追跡法を用いた新たな検査法：Muscle velocity recovery cycleとMScan (2019)
  • Author(s): 金井 数明
  • Organizer: 第49回日本臨床神経生理学会学術大会
  • Invited
• [Presentation] 遺伝性タウオパチーにおける運動神経軸索興奮特性変化 (2019)
  • Author(s): 金井 数明、中里 朋子、下 泰司、 大山 彦光、服部 信孝
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] 筋萎縮性側索硬化症における早期診断・早期治療開始の意義とその課題 (2019)
  • Author(s): 金井 数明
  • Organizer: 第60回日本神経学会学術大会
  • Invited
• [Presentation] Motor axonal abnormalities in anti-MAG neuropathy (2018)
  • Author(s): Kanai K, Nakazato T, Shimo Y, Oyama G, Hattori N.
  • Organizer: 31st International Congress of Clinical Neurophysiology
  • Int'l Joint Research
• [Presentation] Abnormalities of motor axonal properties in amyotrophic lateral sclerosis (2018)
  • Author(s): Nakazato T, Kanai K, Oyama G, Shimo Y, Hattori N.
  • Organizer: 31st International Congress of Clinical Neurophysiology
  • Int'l Joint Research
• [Presentation] Therehold tracking法を用いた神経軸索興奮特性検査 (2018)
  • Author(s): 金井 数明、中里 朋子、服部 信孝
  • Organizer: 第48回日本臨床神経生理学術大会
  • Invited
• [Presentation] 多系統萎縮症における感覚神経の軸索興奮特性 (2018)
  • Author(s): 金井 数明、中里 朋子、大山 彦光、下 泰司、服部 信孝
  • Organizer: 第48回日本臨床神経生理学術大会
• [Presentation] Latent addition法を用いたALSにおける持続性Na+電流上昇と病気進展についての検討 (2018)
  • Author(s): 金井 数明、横田 隆徳、澁谷 和幹、中里 朋子、叶内 匡、大山 彦光、下 秦司、 桑原 聡3、服部 信孝
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 運動神経軸索のNa+および;K+電流変化はALSにおける病気の進展速度に関与する (2018)
  • Author(s): 中里 朋子, 金井 数明, 大山 彦光, 下 泰司,服部 信孝
  • Organizer: 第59回日本神経学会学術大会
• [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