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Rho-kinase inhibitor : a novel therapeutic approach for multiple sclerosis

Research Project

Project/Area Number 19590996
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKyushu University

Principal Investigator

MINOHARA Motozumi  Kyushu University, 大学病院, 講師 (70398113)

Co-Investigator(Kenkyū-buntansha) KAWAMURA Nobutoshi  九州大学, 医学研究院, 学術研究員 (00432930)
河野 祐治  九州大学, 大学病院, 講師 (20333479)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords多発性硬化症 / Rho-kinase / 低分子量GTPase / 実験的自己免疫性脳脊髄炎 / fasudil / EAE / 自己反応性T細胞 / Rho
Research Abstract

我々は、Rho-kinase 阻害剤であるfasudil が、多発性硬化症(MS)の動物モデルである実験的自己免疫性脳脊髄炎(EAE)に対して、予防的効果や治療的効果があることを報告している。さらに、実験的自己免疫性神経炎(EAN)においても同様の効果が認められており、自己反応性T 細胞はいずれもTh1への分化が抑制されていた。Rho-kinase 阻害剤はP38のリン酸化を増大させることで、Th2 へのシフトを誘導することが示された。Rho-kinase阻害剤であるfasudilは、既に我が国では「くも膜下出血術後の脳血管攣縮およびこれに伴う脳虚血症状」に対して使用されている薬剤であり、その安全性は確立している。以上のことからも、Rho-kinase 阻害薬はMSの新規治療法として効果が期待される。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (58 results)

All 2009 2008 2007 Other

All Journal Article (28 results) (of which Peer Reviewed: 27 results) Presentation (26 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Helicobacter pylori is a potential protective factor against conventional type multiple sclerosis in the Japanese population2009

    • Author(s)
      Li W, Minohara M, Su JJ, Matsuoka T, Osoegawa M, Ishizu T, Kira J
    • Journal Title

      J Neuroimmunol 184

      Pages: 227-231

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increase of CD4^+ TNFα^+ IL-2^- T cells in cerebrospinal fluid of multiple sclerosis patients2009

    • Author(s)
      Shi N, Kawano Y, Matsuoka T, Mei F-J, Ishizu T, Ohyagi Y, Kira J
    • Journal Title

      Multiple Sclerosis 15

      Pages: 120-123

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody2009

    • Author(s)
      Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, Kira J
    • Journal Title

      Multiple Sclerosis 15

      Pages: 304-310

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of the HLADPB1^*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders2009

    • Author(s)
      Matsushita T, Matsuoka T, Isobe N, Kawamura Y, Minohara M, Shi N, Nishimura Y, Ochi H, Kira J
    • Journal Title

      Tissue Antigens 72

      Pages: 171-176

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increase of CD4^+ TNFα^+IL-2^- T cells in cerebrospinal fluid of multiplesclerosis patients.2009

    • Author(s)
      Shi N, et al
    • Journal Title

      Mult Scle 15

      Pages: 120-123

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HYypercomplementemia at relapse in patients with anti-aquaporin-4 ant〓body.2009

    • Author(s)
      Doi H, et al
    • Journal Title

      Mult Scler 15

      Pages: 304-310

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of the HLA-DPBl*0501 allele with anti-aquaporin-4 antibody in Japanese patients with idiopathic central nervous system demyelinating disorders.2009

    • Author(s)
      Matsushita T, et al
    • Journal Title

      Tissue Antigens 73

      Pages: 171-176

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior periventricular linear lesions in optic-spinal multiple sclerosis : a combined neuroimaging and neuropathological study2008

    • Author(s)
      Matsushita T, Matsuoka T, Ishizu T, Kikuchi H, Osoegawa M, Kawano Y, Mihara F, Ohyagi Y, Kira J
    • Journal Title

      Multiple Sclerosis 14

      Pages: 343-53

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings2008

    • Author(s)
      Matsuoka T, Matsushita T, Osoegawa M, Ochi H, Kawano Y, Mihara F, Ohyagi Y, Kira J
    • Journal Title

      J Neurol Sci 266

      Pages: 115-25

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Atopic myelitis with focal amyotrophy : a possible link to Hopkins syndrome2008

    • Author(s)
      Kira J, Isobe N, Kawano Y, Osoegawa M, Ohyagi Y, Mihara F, Murai H
    • Journal Title

      J Neurol Sci 169

      Pages: 143-51

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis2008

    • Author(s)
      Matsuoka T, Matsushita T, Osoegawa M, Kawano Y, Minohara M, Mihara F, Nishimura Y, Ohyagi Y, Kira J
    • Journal Title

      Multiple Sclerosis 14

      Pages: 1181-1190

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of myelitis2008

    • Author(s)
      Tanaka M, Matsushita T, Tateishi T, Ochi H, Kawano Y, Mei F-J, Minohara M, Murai H, Kira J
    • Journal Title

      Neurology 71

      Pages: 974-981

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intrathecal upregulation of IFN-γ and MIP-Iβ in juvenile muscular atrophy of the distal upper extremity2008

    • Author(s)
      Tanaka M, Ishizu T, Ochi H, Kawano Y, Ohyagi Y, Kira J
    • Journal Title

      J Neurol Sci 275

      Pages: 74-77

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of myelitis.2008

    • Author(s)
      Tanaka M, et al
    • Journal Title

      Neurology 71

      Pages: 974-981

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings.2008

    • Author(s)
      Matsuoka T, et al
    • Journal Title

      J Neurol Sci 266

      Pages: 115-125

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior periventricular linear lesions in optic-spinal multiple sclerosis : a combined neuroimaging and neuropathological study.2008

    • Author(s)
      Matsushita T, et al
    • Journal Title

      Mult Scler 21

      Pages: 343-353

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of the HLA-DEB1 alleles with characteristic MRI features of Asian multiple sclerosis.2008

    • Author(s)
      Matsuoka T, et al
    • Journal Title

      Mult Scler 14

      Pages: 1181-1190

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior periventricular linear lesions in optic-spinal multiple sclerosis:a combined neuroimaging and neuropathological study2008

    • Author(s)
      Matsushita T, et. al.
    • Journal Title

      Mult Scler 21(In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atopic myelitis with focal amyotrophy:A possible link to Hopkins syndrome2008

    • Author(s)
      Kira J, et. al.
    • Journal Title

      J Neurol Sci 21(In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese2007

    • Author(s)
      Matsuoka T, Matsushita T, Kawano Y, Osoegawa M, Ochi H, Ishizu T, Minohara M, Kikuchi H, Mihara F, Ohyagi Y, Kira J
    • Journal Title

      Brain 130

      Pages: 1206-1223

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Helicobacter pylori infection is a potential protective factor against conventional multiple sclerosis in the Japanese population2007

    • Author(s)
      Li W, et. al.
    • Journal Title

      J Neuroimmunol 184

      Pages: 227-231

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions inmultiple sclerosis in Japanese2007

    • Author(s)
      Matsuoka T, et. al.
    • Journal Title

      Brain 130

      Pages: 1206-1223

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in Apc(Min/+)mice2007

    • Author(s)
      Yokomine K, et. al.
    • Journal Title

      Cancer Sci 98

      Pages: 1930-1935

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autonomous proliferation of HTLV-CD4+T cell clones derived from human T cell leukemia virus type I(HTLV-I)-associated myelopathy patients2007

    • Author(s)
      Miyano-Kurosaki N, et. al.
    • Journal Title

      Microbiol Immunol 51

      Pages: 235-242

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Slowly progressive distal muscular atrophy of the bilateral upper limbs(O'Sullivan-McLeod syndrome)partially alleviated by intravenous immunoglobulin therapy2007

    • Author(s)
      Kawano Y, et. al.
    • Journal Title

      intern Med 46

      Pages: 515-518

    • NAID

      130000078746

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 162007

    • Author(s)
      Iwaki A, et. al.
    • Journal Title

      J Med Genet 45

      Pages: 32-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings2007

    • Author(s)
      Matsuoka T, et. al.
    • Journal Title

      J neurol Sci 266

      Pages: 115-125

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative optico spinal multiple sclerosis in Japanese

    • Author(s)
      Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu X-M, Yoshiura T, Nakao Y, Ishizu T, Kira J
    • Journal Title

      Multiple Sclerosis (in press)

    • Related Report
      2008 Final Research Report
  • [Presentation] 末梢免疫担当細胞におけるbrain-derived neurotrophicfactor (BDNF)産生能と多発性硬化症(MS)病態との関連2009

    • Author(s)
      吉村怜、越智博文、三野原元澄、吉良潤一
    • Organizer
      第21回日本神経免疫学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-12
    • Related Report
      2008 Final Research Report
  • [Presentation] FACS を用いた高感度抗AQP4抗体の検出 : サブクラス解析を含めて2009

    • Author(s)
      磯部紀子、河野祐治、松下拓也、松岡健、河村信利、三野原元澄、吉良潤一
    • Organizer
      第21回日本神経免疫学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-12
    • Related Report
      2008 Final Research Report
  • [Presentation] 多発性硬化症におけるヘリコバクターピロリ感染の影響2009

    • Author(s)
      三野原元澄、李巍、松下拓也、松岡健、磯部紀子、吉良潤一
    • Organizer
      第21回日本神経免疫学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-12
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Hypercomplementemia at Relapse in Patients with Anti-Aquaporin-4 Antibody2008

    • Author(s)
      Doi H, Matsushita T, Isobe N, Matsuoka M, Minohara M, Ochi H, Kira J.
    • Organizer
      PACTRIMS for Treatment and Research in Multiple Sclerosis
    • Place of Presentation
      Kuala Lumpur
    • Year and Date
      2008-11-21
    • Related Report
      2008 Final Research Report
  • [Presentation] Distinct cerebrospinal fluid cytokine/chemokine profiles in opticospinal multiple sclerosis,atopic myelitis and other causes of myelitis2008

    • Author(s)
      Kira J, Tanaka M, Matsushita T, Matuoka T, Tateishi T, Minohara M.
    • Organizer
      WORLD CONGRESS ON TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2008-09-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 抗CLDND1抗体陽性多発性硬化症の臨床像2008

    • Author(s)
      三野原元澄ら
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] FACSによる抗native AQP4抗体の高感度検出法の開発2008

    • Author(s)
      河野祐治、松下拓也、松岡健、河村信利、三野原元澄、吉良潤一
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-15
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 抗体価と臨床像からみた抗aquaporin-4(AQP4)抗体の意義2008

    • Author(s)
      松岡健、松下拓也、河野祐治、三野原元澄、吉良潤一
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-15
    • Related Report
      2008 Final Research Report
  • [Presentation] 抗AQP4抗体価からみた日本人多発性硬化症患者の病像・画像所見の特徴 : 抗AQP4抗体の役割について2008

    • Author(s)
      松岡健、松下拓也、河野祐治、三野原元澄、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 抗aquaporin-4(AQP4)抗体価による多発性硬化症の免疫学的・遺伝学的背景の差異2008

    • Author(s)
      河野祐治、松下拓也、松岡健、史楠、三野原元澄、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] FACSを用いた高感度抗AQP4抗体検出法の開発2008

    • Author(s)
      河野祐治、松下拓也、松岡健、史楠、河村信利、三野原元澄、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 多発性硬化症におけるconformational にAQP1を認識する抗体の検索2008

    • Author(s)
      河村信利、松下拓也、三野原元澄、河野祐治、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 抗CLDND1抗体陽性多発性硬化症と抗AQP4抗体との関連2008

    • Author(s)
      三野原元澄、松下拓也、松岡健、河村信利、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] MS 髄液におけるCD4^+TNFα^+IL2^-T細胞サブセット異常2008

    • Author(s)
      史楠、河野祐治、梅風君、松岡健、三野原元澄、越智博文、吉良潤一
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 抗aquaporin-4 (AQP4)抗体価による多発性硬化症の免疫学的・遺伝学的背景の差異2008

    • Author(s)
      河野祐治ら
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 抗CLDND1抗体陽性多発性硬化症を抗AQP4抗体との関連2008

    • Author(s)
      三野原元澄ら
    • Organizer
      第20回日本神経免疫学会学術集会
    • Place of Presentation
      新潟
    • Year and Date
      2008-04-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 実験的自己免疫性神経炎にたいするRhi-kinase阻害剤の効果2007

    • Author(s)
      三野原 元澄, 他
    • Organizer
      日本末梢神経学会
    • Place of Presentation
      弘前
    • Year and Date
      2007-08-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] 日本人多発性硬化症における抗aquaporin-4抗体陽性率と陽性例と陰性例との臨床像の比較2007

    • Author(s)
      松下拓也、河野祐治、松岡健、小副川学、三野原元澄、吉良潤一
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 臨床型と抗aquaporin-4(AQP4)抗体からみた日本人多発性硬化症の長大な脊髄病巣の解析2007

    • Author(s)
      松岡健、松下拓也、河野祐治、小副川学、三野原元澄、吉良潤一
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本人多発性硬化症におけるMRI所見とHLAクラスII遺伝子多型との相関2007

    • Author(s)
      三野原元澄、松岡健、松下拓也、小副川学、越智博文、吉良潤一
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本人多発性硬化症における抗CLDND1抗体の意義2007

    • Author(s)
      三野原元澄、松下拓也、松岡健、小副川学、村井弘之、吉良潤一
    • Organizer
      第19回日本神経免疫学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2007-04-12
    • Related Report
      2008 Final Research Report
  • [Presentation] 自験多発性硬化症患者の画像所見とHLAとの関連 : 連続121例の解析結果2007

    • Author(s)
      松岡健、三野原元澄、松下拓也、小副川学、越智博文、吉良潤一
    • Organizer
      第19回日本神経免疫学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2007-04-12
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本人多発性硬化症における抗CLDND1抗体の意義2007

    • Author(s)
      三野原 元澄 他
    • Organizer
      日本神経免疫学会
    • Place of Presentation
      金沢
    • Year and Date
      2007-04-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] アトピー性脊髄炎と若年性一側性上肢筋萎縮症での髄液サイトカインプロフィール2007

    • Author(s)
      河野 祐治, 他
    • Organizer
      日本神経免疫学会
    • Place of Presentation
      金沢
    • Year and Date
      2007-04-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] Serum autoantibodies to claudin domain containing 1 protein in Japanese patients with multiple sclerosis2007

    • Author(s)
      Minohara M, Matsuoka T, Matsushita T, Kawamura N, Kira J
    • Organizer
      Congress of the European Committee for Treatment and Research in Multiple Sclerosis
    • Place of Presentation
      Prague
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 日本人多発性硬化症におけるMRI所見とHLAクラスII遺伝子多型との相関2007

    • Author(s)
      三野原 元澄 他
    • Organizer
      日本神経学会
    • Place of Presentation
      名古屋
    • Related Report
      2007 Annual Research Report
  • [Book] 多発性硬化症の診断と治療2008

    • Author(s)
      三野原元澄, 吉良潤一
    • Total Pages
      285
    • Publisher
      新興医学出版
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/neuro/

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/neuro/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/neuro/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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