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Therapeutic development for amyotrophic lateral sclerosis using sodium channel blockers, modulating motor nerve excitability

Research Project

Project/Area Number 17K16110
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionChiba University

Principal Investigator

Shibuya Kazumoto  千葉大学, 医学部附属病院, 助教 (90507360)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords筋萎縮性側索硬化症 / 運動神経興奮性 / Na電流 / イオンチャネル / 神経興奮性 / Naチャネル阻害薬 / ナトリウム電流 / ナトリウムチャネルブロッカー / 臨床試験
Outline of Final Research Achievements

Hyperexcitability in the motor neuron potentially contributes to motor neuron death in amyotrophic lateral sclerosis (ALS). To support this hypotheis, I reported the following findings. Muscle cramps, which indicate motor nerve hyperexcitability, were related to rapid progression in ALS. Especially, cramps followed by muscle weakness was associated with rapid progression. Moreover, we examined the relationship between cortical excitability and disease stage and showed progressive hyperexcitability. I have also performed a clinical trial utilizing Lacosamide and have tried to disclose its effects for nerve excitability in ALS patients.

Academic Significance and Societal Importance of the Research Achievements

今回、ALS運動神経興奮性増大とALS進行速度との関係を更に明らかにすることができた。加えて、ALS運動皮質興奮性の自然経過を示すことができた。また、Naチャネル阻害薬が神経興奮性変化に寄与するかを検討する臨床試験を実施することができた。ALSは発症から約3年で呼吸不全により死亡する非常に過酷な神経難病である。現在治療薬として臨床応用されている薬剤の生存期間延長効果は数ヶ月と極めて限定的であり、新規治療薬の開発は急務である。今回の結果は、イオンチャネル阻害薬がALS治療薬候補となる得るかを検討したものであり、将来の治療薬開発に役立つ基盤的データとなる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (40 results)

All 2020 2019 2018 2017

All Journal Article (21 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 21 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Funded Workshop (2 results)

  • [Journal Article] Striatal Encephalitis in Neuropsychiatric Systemic Lupus Erythematosus2020

    • Author(s)
      Nakamura Keigo、Sugiyama Atsuhiko、Shibuya Kazumoto、Kuwabara Satoshi
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 4 Pages: 589-590

    • DOI

      10.2169/internalmedicine.3693-19

    • NAID

      130007798423

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-02-15
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different distribution of demyelination in chronic inflammatory demyelinating polyneuropathy subtypes2020

    • Author(s)
      Shibuya Kazumoto、Tsuneyama Atsuko、Misawa Sonoko、Sekiguchi Yukari、Beppu Minako、Suichi Tomoki、Suzuki Yo-ichi、Nakamura Keigo、Kano Hiroki、Kuwabara Satoshi
    • Journal Title

      Journal of Neuroimmunology

      Volume: 341 Pages: 577170-577170

    • DOI

      10.1016/j.jneuroim.2020.577170

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment response and prognosis of POEMS syndrome coexisting with Castleman disease.2020

    • Author(s)
      Suichi T, Misawa S, Sekiguchi Y, Shibuya K, Tsuneyama A, Suzuki YI, Nakamura K, Kano H, Kuwabara S.
    • Journal Title

      J Neurol Sci.

      Volume: 413 Pages: 116771-116771

    • DOI

      10.1016/j.jns.2020.116771

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognosis of amyotrophic lateral sclerosis patients undergoing tracheostomy invasive ventilation therapy in Japan2020

    • 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

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hidden Charcot-Marie-Tooth 1A as Revealed by Peripheral Nerve Imaging2019

    • Author(s)
      Shibuya Kazumoto、Yoshida Toshiki、Misawa Sonoko、Sekiguchi Yukari、Beppu Minako、Amino Hiroshi、Suzuki Yo-ichi、Suichi Tomoki、Tsuneyama Atsuko、Nakamura Keigo、Kuwabara Satoshi
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 21 Pages: 3157-3161

    • DOI

      10.2169/internalmedicine.3040-19

    • NAID

      130007740734

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-11-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dropped Head in Sporadic Late-onset Nemaline Myopathy2019

    • Author(s)
      Nakamura K, Shibuya K, Nishino I, Kuwabara S
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 13 Pages: 1967-1968

    • DOI

      10.2169/internalmedicine.2247-18

    • NAID

      130007672126

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-07-01
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Membrane property changes in most distal motor axons in chronic inflammatory demyelinating polyneuropathy2019

    • Author(s)
      Amino Hiroshi、Shibuya Kazumoto、Misawa Sonoko、Sekiguchi Yukari、Beppu Minako、Suichi Tomoki、Suzuki Yo‐ichi、Tsuneyama Atsuko、Kuwabara Satoshi
    • Journal Title

      Muscle & Nerve

      Volume: 61 Issue: 2 Pages: 238-242

    • DOI

      10.1002/mus.26744

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence, clinical profiles, and prognosis of POEMS syndrome in Japanese nationwide survey.2019

    • Author(s)
      Suichi T, Misawa S, Beppu M, Takahashi S, Sekiguchi Y, Shibuya K, Amino H, Tsuneyama A, Suzuki YI, Nakamura K, Sato Y, Kuwabara S.
    • Journal Title

      Neurology.

      Volume: 93 Issue: 10

    • DOI

      10.1212/wnl.0000000000008062

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A study supporting possible expression of inward-rectifying potassium channel 2.1 channels in peripheral nerve in a patient with Andersen-Tawil syndrome.2019

    • Author(s)
      Shibuya K, Tsuneyama A, Beppu M, Misawa S, Sekiguchi Y, Amino H, Suzuki YI, Suichi T, Nakamura K, Kuwabara S
    • Journal Title

      Muscle and Nerve

      Volume: 59 Issue: 4 Pages: 133-137

    • DOI

      10.1002/mus.26430

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Japanese early-stage trial of high-dose methylcobalamin for amyotrophic lateral sclerosis (JETALS): Protocol for a randomized controlled trial2018

    • 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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel autoantibodies against the proteasome subunit PSMA7 in amyotrophic lateral sclerosis2018

    • Author(s)
      Sugimoto Kazuo、Hiwasa Takaki、Shibuya Kazutomo、Hirano Shigeki、Beppu Minako、Isose Sagiri、Arai Kimihito、Takiguchi Masaki、Kuwabara Satoshi、Mori Masahiro
    • Journal Title

      Journal of Neuroimmunology

      Volume: 325 Pages: 54-60

    • DOI

      10.1016/j.jneuroim.2018.09.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proposal of new clinical diagnostic criteria for POEMS syndrome2018

    • Author(s)
      Suichi Tomoki、Misawa Sonoko、Sato Yasunori、Beppu Minako、Sakaida Emiko、Sekiguchi Yukari、Shibuya Kazumoto、Watanabe Keisuke、Amino Hiroshi、Kuwabara Satoshi
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 90 Issue: 2 Pages: 133-137

    • DOI

      10.1136/jnnp-2018-318514

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prodromal muscle cramps predict rapid motor functional decline in amyotrophic lateral sclerosis2018

    • Author(s)
      Shibuya Kazumoto、Misawa Sonoko、Sekiguchi Yukari、Beppu Minako、Amino Hiroshi、Suichi Tomoki、Suzuki Yo-ichi、Tsuneyama Atsuko、Kuwabara Satoshi
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 90 Issue: 2 Pages: 242-243

    • DOI

      10.1136/jnnp-2018-318446

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain.2018

    • Author(s)
      Watanabe K, Hirano S, Kojima K, Nagashima K, Mukai H, Sato T, Takemoto M, Matsumoto K, Iimori T, Isose S, Omori S, Shibuya K, Sekiguchi Y, Beppu M, Amino H, Suichi T, Yokote K, Uno T, Kuwabara S, Misawa S.
    • Journal Title

      Journal of Neurology Neurosurgry Psychiatry

      Volume: 印刷中 Issue: 10 Pages: 1082-1087

    • DOI

      10.1136/jnnp-2017-316601

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ectopic impulse generation in peripheral nerve hyperexcitability syndromes and amyotrophic lateral sclerosis.2018

    • Author(s)
      Noto YI, Simon NG, Selby A, Garg N, Shibuya K, Shahrizaila N, Huynh W, Matamala JM, Dharmadasa T, Park SB, Vucic S, Kiernan MC
    • Journal Title

      Clinical Neurophysiology

      Volume: 印刷中 Issue: 5 Pages: 974-980

    • DOI

      10.1016/j.clinph.2018.01.061

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dynamic muscle ultrasound identifies upper motor neuron involvement in amyotrophic lateral sclerosis.2017

    • Author(s)
      Noto YI, Simon N, Shibuya K, Matamala JM, Dharmadasa T, Kiernan MC.
    • Journal Title

      Amyotrophic Lateral Sclerosis Frontotemporal Degeneration

      Volume: 18 Issue: 5-6 Pages: 404-410

    • DOI

      10.1080/21678421.2017.1286355

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The evolution of motor cortical dysfunction in amyotrophic lateral sclerosis.2017

    • Author(s)
      Shibuya K, Simon NG, Geevasinga N, Menon P, Howells J, Park SB, Huynh W, Noto YI, Vucic S, Kiernan MC.
    • Journal Title

      Clinical Neurophysiology

      Volume: 128 Issue: 6 Pages: 1075-1082

    • DOI

      10.1016/j.clinph.2017.03.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of fasciculations in amyotrophic lateral sclerosis: The optimal ultrasound scan time.2017

    • Author(s)
      Noto YI, Shibuya K, Shahrizaila N, Huynh W, Matamala JM, Dharmadasa T, Kiernan MC.
    • Journal Title

      Muscle Nerve

      Volume: 56 Issue: 6 Pages: 1068-1071

    • DOI

      10.1002/mus.25607

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Laterality of motor cortical function measured by transcranial magnetic stimulation threshold tracking.2017

    • Author(s)
      Shibuya K, Park SB, Howells J, Huynh W, Noto YI, Shahrizaila N, Matamala JM, Vucic S, Kiernan MC.
    • Journal Title

      Muscle Nerve.

      Volume: 55 Issue: 3 Pages: 424-427

    • DOI

      10.1002/mus.25372

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pontine Syphilitic Gumma in an HIV-negative Patient2017

    • Author(s)
      Murakawa M, Shibuya K, Sekiguchi Y, Kuwabara S.
    • Journal Title

      Internal Medicine

      Volume: 56 Issue: 13 Pages: 1747-1748

    • DOI

      10.2169/internalmedicine.56.8192

    • NAID

      130006858092

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pain-related evoked potentials after intraepidermal electrical2017

    • Author(s)
      Omori S, Isose S, Misawa S, Watanabe K, Sekiguchi Y, Shibuya K, Beppu M, Amino
    • Journal Title

      Neuroscience Research

      Volume: 印刷中 Pages: 43-48

    • DOI

      10.1016/j.neures.2017.03.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] The split hand sign in spinal and bulbar muscular atrophy2019

    • Author(s)
      Kazumoto Shibuya, Sonoko Misawa, Yukari Sekiguchi, Minako Beppu, Hiroshi Amino, Atsuko Tsuneyama, Yo-ichi Suzuki, Tomoki Suichi, Keigo Nakamura and Satoshi Kuwabara
    • Organizer
      The 30th International Symposium on ALS/MND
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Different distributions of nerve conduction slowing/block in typical and atypical chronic inflammatory demyelinating polyneuropathy2019

    • Author(s)
      Kazumoto Shibuya, Atsuko Tsuneyama, Sonoko Misawa, Yukari Sekiguchi, Hiroshi Amino, Yo-ichi Suzuki, Tomoki Suichi, Keigo Nakamura, Satoshi Kuwabara
    • Organizer
      2019 PNS ANNUAL MEETING
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Split handは球脊髄性筋萎縮症でも認められる2019

    • Author(s)
      澁谷和幹、三澤園子、関口縁、網野寛、水地智基、鈴木陽一、常山篤子、中村圭吾、鵜沢顕之、桑原聡
    • Organizer
      検索結果 ウェブ検索結果 第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 今日から始める神経筋超音波検査2019

    • Author(s)
      澁谷和幹
    • Organizer
      第 37 回日本神経治療学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 多巣性運動性ニューロパチーでは感覚神経も障害を受ける2019

    • Author(s)
      澁谷和幹、三澤園子、関口縁、鈴木陽一、水地智基、常山篤子、狩野裕樹、小島雄太、桑原聡
    • Organizer
      第31回日本神経免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 慢性炎症性脱髄性多発ニューロパチーの臨床病型による脱髄分布の差異2019

    • Author(s)
      澁谷和幹、常山篤子、三澤園子、関口縁、網野寛、鈴木陽一、水地智基、中村圭吾、桑原聡
    • Organizer
      第30回日本末梢神経学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Andersen-Tawil症候群(周期性四肢麻痺)2019

    • Author(s)
      澁谷和幹
    • Organizer
      第49回日本臨床神経生理学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 閾値追跡法を用いた2連発経頭蓋磁気刺激検査の臨床応用2019

    • Author(s)
      澁谷和幹
    • Organizer
      第49回日本臨床神経生理学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 奨励賞受賞記念講演 神経興奮性検査を用いた筋萎縮性側索硬化症の病態解明・新規治療薬開発2019

    • Author(s)
      澁谷和幹
    • Organizer
      第49回日本臨床神経生理学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 閾値追跡法を用いた筋萎縮性側索硬化症運動野および末梢神経興奮性の評価2019

    • Author(s)
      澁谷和幹、鈴木陽一、三澤園子、関口縁、常山篤子、水地智基、中村圭吾、狩野裕樹、桑原聡
    • Organizer
      第49回日本臨床神経生理学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Altered axonal excitability in spinal and bulbar muscular atrophy2018

    • Author(s)
      Kazumoto Shibuya, Sonoko Misawa, Yukari Sekiguchi, Yo-ichi Suzuki, Hiroshi Amino, Tomoki Suichi, Atsuko Tsuneyama, Satoshi Kuwabara
    • Organizer
      31st International Congress of Clinical Neurophysiology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 球脊髄性筋萎縮症の運動神経軸索興奮性変化2018

    • Author(s)
      澁谷和幹、三澤園子、関口縁、網野寛、水地智基、鈴木陽一、常山篤子、桑原聡
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 球脊髄性筋萎縮症における運動神経軸索興奮性変化2018

    • Author(s)
      澁谷和幹、三澤園子、関口縁、網野寛、水地智基、鈴木陽一、常山篤子、中村圭吾、鵜沢顕之、桑原聡
    • Organizer
      第48回日本臨床神経生理学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Recent advances and future perspective of nerve excitability testing2017

    • Author(s)
      Kazumoto Shibuya
    • Organizer
      6th Asian-Oceanian Congress of Clinical Neurophysiology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The origin of fasciculation in ALS; direct correlation between axonal excitability and fasciculation2017

    • Author(s)
      Kazumoto Shibuya, Sonoko Misawa, Hideki Kimura, Yu-ichi Noto, Yukari Sekiguchi, Yuta Iwai, Toshio Shimizu, Toshiki Mizuno, Masanori Nakagawa and Satoshi Kuwabara
    • Organizer
      International Symposium on ALS/MND
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prodromal muscle cramps predict rapid functional decline in amyotrophic lateral sclerosis2017

    • Author(s)
      Kazumoto Shibuya, Sonoko Misawa, Yukari Sekiguchi, Minako Beppu, Keisuke Watanabe, Hiroshi Amino, Tomoki Suichi and Satoshi Kuwabara
    • Organizer
      The XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 筋萎縮性側索硬化症における線維束性収縮と軸索興奮性の関係2017

    • Author(s)
      澁谷和幹、三澤園子、木村英紀、能登祐一、関口縁、岩井雄太、清水俊夫、中川正法、水野敏樹、桑原聡
    • Organizer
      第47回日本臨床神経生理学会学術大会
    • Related Report
      2017 Research-status Report
  • [Funded Workshop] 2019 PNS Annual Meeting2019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] 30th International Symposium on ALS/MND2019

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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