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Treatment of animal model of ALS with anti GM-CSF antibody

Research Project

Project/Area Number 23591244
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionOsaka University

Principal Investigator

OKUNO Tatsusada  大阪大学, 医学(系)研究科(研究院), 助教 (00464248)

Co-Investigator(Kenkyū-buntansha) 中辻 裕司  大阪大学, 医学系研究科, 講師 (20332744)
Co-Investigator(Renkei-kenkyūsha) 多田 智  大阪大学, 医学系研究科 (70626530)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsALS / GM-CSF / M1/M2 / ミクログリア / 炎症 / JAK2阻害剤 / M1/M2 / M1/M2 / ALS / セマフォリン
Research Abstract

To inhibit GM-CSF-mediated M1 activation in ALS model mice (G93A mSOD1 mice), we used JAK2 inhibitor(R723). Orally adminstered JAK2 inhibitor significantly reduced the number of inflammatory monocytes, as well as the expression level of IFN-gamma and iNOS in the spinal cord tissue of ALS model mice. However, disease progression and survival of mSOD1G93A were not altered by administration of R723.The expression levels of Il-1, Il-6, tumor necrosis factor (TNF), and NADPH oxidase 2 (NOX2) were not altered by R723 treatment.Furthermore, R723 suppressed the expression of Retnla, a marker of neuroprotective M2 microglia.In conclusion,oral administration of JAK2 inhibitor was not effective against ALS symptoms in mSOD1G93A mice, although it suppressed production of several inflammatory molecules. Coincidental suppression of M2 microglia and failure to inhibit critical inflammatory molecules might have contributed to this result.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (19 results) (of which Peer Reviewed: 9 results) Presentation (5 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Sema4A inhibits the therapeutic effect of IFN-βin EAE2014

    • Author(s)
      Koda T, Okuno T, Takata K, Honorat JA, Kinoshita M, Tada S, Moriya M, Sakoda S, Mochizuki H, Kumanogoh A, Nakatsuji Y
    • Journal Title

      J Neur oimmunol

      Volume: 5728(14) Pages: 2-2

    • Related Report
      2013 Final Research Report
  • [Journal Article] Early pathological alterations of lower lumber cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model2014

    • Author(s)
      Mori Y, Murakami M, Arima Y, Zhu D, Terayama Y, Komai Y, Nakatsuji Y, Kamimura D, Yoshioka Y
    • Journal Title

      Int Immunol

      Volume: 26(2) Pages: 93-101

    • Related Report
      2013 Final Research Report
  • [Journal Article] Sema4A inhibits the therapeutic effect of IFN-β in EAE.2014

    • Author(s)
      Koda T, Okuno T, Takata K, Honorat JA, Kinoshita M, Tada S, Moriya M, Sakoda S, Mochizuki H, Kumanogoh A, Nakatsuji Y
    • Journal Title

      J Neuroimmunol.

      Volume: 268(1-2) Issue: 1-2 Pages: 43-9

    • DOI

      10.1016/j.jneuroim.2013.12.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of Sema4A in Multiple Sclerosis and IFN-βTherapy Efficacy2013

    • Author(s)
      Nakatsuji Y, Okuno T, Koda T, Takata K, Honorat JA, Mochizuki H, Kumanogoh A
    • Journal Title

      Clinical Experimental Neur oimmunology

      Volume: 4 Pages: 274-282

    • Related Report
      2013 Final Research Report
  • [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration2013

    • Author(s)
      Nojima, S., Toyofuku, T., Kamao, H., Ishigami, C., Kaneko, J., Okuno, T., Takamatsu, H., Ito, D., Kang, S., Kimura, T., Yoshida, Y., Morimoto, K., Maeda, Y., Ogata, A., Ikawa, M., Morii, E., Aozasa, K., Takagi, J., Takahashi, M. & Kumanogoh, A
    • Journal Title

      Nature communications

      Volume: 4 Pages: 1406-1406

    • Related Report
      2013 Final Research Report
  • [Journal Article] Disease-association analysis of an inflammation-related feedback loop2013

    • Author(s)
      Murakami M, Harada M, Kamimura D, Ogura H, Okuyama Y, Kumai N, Okuyama A, Singh R, Jiang JJ, Atsumi T, Shiraya S, Nakatsuji Y, Kinoshita M, Kohsaka H, Nishida M, Sakoda S, Miyasaka N, Yamauchi-Takihara K, Hirano T
    • Journal Title

      Cell Rep

      Volume: 3(3) Pages: 946-59

    • Related Report
      2013 Final Research Report
  • [Journal Article] Xanthine oxidase mediates axonal and myelin loss in a murine model of multiple sclerosis2013

    • Author(s)
      Honorat JA, Kinoshita M, Okuno T, Takata K, Koda T, Mochizuki H, Nakatsuji Y
    • Journal Title

      PLoS One

      Volume: 8(8)

    • Related Report
      2013 Final Research Report
  • [Journal Article] BAFF controls neural cell survival through BAFF receptor2013

    • Author(s)
      Tada S, Yasui T, Nakatsuji Y Okuno T, Koda T, Mochizuki H, Sakoda S, Kikutani H
    • Journal Title

      PLoS One

      Volume: 8(7)

    • Related Report
      2013 Final Research Report
  • [Journal Article] BAFF controls neural cell survival through BAFF receptor.2013

    • Author(s)
      Tada S, Yasui T, Nakatsuji Y, Okuno T, Koda T, Mochizuki H, Sakoda S, Kikutani H
    • Journal Title

      PLoS One.

      Volume: 29;8(7) Issue: 7 Pages: e70924-e70924

    • DOI

      10.1371/journal.pone.0070924

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xanthine oxidase mediates axonal and myelin loss in a murine model of multiple sclerosis.2013

    • Author(s)
      Honorat JA, Kinoshita M, Okuno T, Takata K, Koda T, Tada S, Shirakura T, Fujimura H, Mochizuki H, Sakoda S, Nakatsuji Y.
    • Journal Title

      PLoS One.

      Volume: 8;8(8) Issue: 8 Pages: e71329-e71329

    • DOI

      10.1371/journal.pone.0071329

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration2013

    • Author(s)
      Nojima S, et al.
    • Journal Title

      Nat Commun

      Volume: 4 Issue: 1 Pages: 1406-1406

    • DOI

      10.1038/ncomms2420

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of progressive ataxia and palatal tremor (PAPT) with ear clicks.2013

    • Author(s)
      Sumikura H, Okuno T, Takahashi MP, Araki K, Kitagawa K, Mochizuki H.
    • Journal Title

      Clinical Neurology

      Volume: 53(3) Pages: 224-8

    • NAID

      40019608624

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of chronic active Epstein-Barr virus infection associated with recurrent cerebellar ataxia and skin eruptions.2013

    • Author(s)
      Araki K, Okuno T, Honorat JA, Kinoshita M, Takahashi MP, Mizuki M, Kitagawa K, Mochizuki H
    • Journal Title

      Clinical Neurology

      Volume: 53(2) Pages: 119-24

    • NAID

      40019583031

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevation of Sema4A implicates Th cell skewing and the efficacy of IFN-βtherapy in multiple sclerosis2012

    • Author(s)
      Nakatsuji Y, Okuno T, Moriya M, Sugimoto T, Kinoshita M, Takamatsu H, i Nojima S, Kimura T, Kang S, Ito D, Nakagawa Y, Toyofuku T, Takata K, Nakano M, Kubo M, Suzuki S, Matsui-Hasumi A, Uto-Konomi A, Ogata A, Mochizuki H, Sakoda S, Kumanogoh A
    • Journal Title

      Journal of Immunology

      Volume: 188 Pages: 4858-65

    • Related Report
      2013 Final Research Report
  • [Journal Article] Elevation of Sema4A implicates Th cell skewing and the efficacy of interferon-β therapy in multiple sclerosis.2012

    • Author(s)
      Nakatsuji Y, Okuno T et al.
    • Journal Title

      Journal of Immunology.

      Volume: 188(10) Pages: 4858-6

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal epithelial cell-derived semaphorin 7A negatively regulates development of colitis via αvβ1 integrin.2012

    • Author(s)
      Kang S, Okuno T, Takegahara N, Takamatsu H, Nojima S, Kimura T, Yoshida Y, Ito D, Ohmae S, You DJ, Toyofuku T, Jang MH, Kumanogoh A
    • Journal Title

      Journal of Immunology

      Volume: 188(3) Pages: 1108-1116

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of immune semaphorins in multiple sclerosis2011

    • Author(s)
      Okuno T, Nakatsuji Y, Kumanogoh A
    • Journal Title

      FEBS Letter

      Volume: 585 Pages: 3829-35

    • Related Report
      2013 Final Research Report
  • [Journal Article] RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis2011

    • Author(s)
      Muramatsu R, , Kubo T, Mori M, Nakamura Y, Fujita Y, Akutsu T, Okuno T, Taniguchi J, Kumanogoh A, Yoshida M, Mochizuki H, , Kuwabara S, Yamashita T
    • Journal Title

      Nature Medicine

      Volume: 17 Pages: 488-94

    • Related Report
      2013 Final Research Report
  • [Journal Article] The role of immune semaphorins in multiple sclerosis.2011

    • Author(s)
      Okuno T, Nakatsuji Y, Kumanogoh A.
    • Journal Title

      FEBS Letters.

      Volume: 585 Pages: 3829-3835

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] BAFF controls neural cell survival through BAFF receptor2013

    • Author(s)
      Tada S, Yasui T, Nakatsuji Y, Okuno T, Mochizuki H, Sakoda S, Kikutani H
    • Organizer
      XXI WORLD CONGRESS OF NEUROLOGY
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2013 Final Research Report
  • [Presentation] プロスタグランジンI2アゴニストであるONO-1301はALSモデル動物の神経変性を抑制する2013

    • Author(s)
      多田智、安居輝人、奥野龍禎、中辻裕司、酒井芳紀、宮川繁、澤芳樹、菊谷仁、佐古田三郎、望月秀樹
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京(ポスター)
    • Related Report
      2013 Final Research Report
  • [Presentation] BAFF controls neural cell survival through BAFF receptor.2013

    • Author(s)
      Tada S, Yasui T, Nakatsuji Y, Okuno T, Mochizuki H, Sakoda S, Kikutani H
    • Organizer
      XXI WORLD CONGRESS OF NEUROLOGY
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2013 Annual Research Report
  • [Presentation] Regulation of microglial axis by T lymphocytes in neurodegenerative disorders

    • Author(s)
      奥野龍禎
    • Organizer
      脳内環境若手シンポジウム
    • Place of Presentation
      京都平安ホテル
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ALSモデルマウスにおけるM1/M2活性化とその制御による治療の試み

    • Author(s)
      奥野龍禎
    • Organizer
      日本神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Remarks] 本研究も含め大阪大学神経内科の神経免疫グループの業績を公開

    • URL

      http://www.med.osaka-u.ac.jp/pub/neurol/myweb6/group03.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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