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2013 Fiscal Year Annual Research Report

血管内投与型AAVベクターによる神経変性症の遺伝子治療

Research Project

Project/Area Number 23590473
Research InstitutionJichi Medical University

Principal Investigator

村松 慎一  自治医科大学, 医学部, 教授 (10239543)

Keywords神経変性疾患 / 遺伝子治療
Research Abstract

びまん性レビー小体病(DLB)と前頭側頭葉変性症(FTLD)は, 認知症の原因となる神経変性疾患としてアルツハイマー病についで多い. DLBでは広範な中枢神経領域においてα-synucleinが蓄積している. TDP-43は, FTLDのユビキチン陽性封入体の成分として同定され, 続いて筋萎縮性側索硬化症(ALS)において遺伝子変異が見いだされた. 以来, α-synucleinとTDP-43は神経変性疾患の病態解明の鍵となる分子として注目されている. 本研究では, 申請者が開発した血管内投与により広範な中枢神経領域の神経細胞に効率よく遺伝子を導入できるアデノ随伴ウイルス(AAV)ベクターを応用した. TDP-43を神経細胞に発現させたモデルマウスを作製しその病態を解析している. さらに血管内投与型AAVベクターを応用した新規遺伝子治療法を開発した. 球脊髄性筋萎縮症(SBMA)のモデルマウスの脊髄運動神経細胞でmiR-196aを発現させることにより異常アンドロゲン受容体蛋白が減少し症状が改善した. また, Alzheimer病モデルマウスの脳内の広範な領域でAβ分解酵素のNeprilysin を発現させることにより認知機能の改善効果を得た. さらに, ALSのモデルマウスの脊髄運動神経細胞でRNA編集酵素のADAR2を発現させ症状の進行を抑制した.

  • Research Products

    (19 results)

All 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (11 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Rescue of amyotrophic lateral sclerosis phenotype in a mouse model by intravenous AAV9-ADAR2 delivery to motor neurons2013

    • Author(s)
      Yamashita T, Chai HL, Teramoto S, Tsuji S, Shimazaki K, Muramatsu S, Kwak S
    • Journal Title

      EMBO Mol Med

      Volume: 5(11) Pages: 1710-1719

    • DOI

      10.1002/emmm.201302935

    • Peer Reviewed
  • [Journal Article] Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency2013

    • Author(s)
      Lee N-C, Shieh Y-D, Chien Y-H, Tzen K-Y, Yu I-S, Chen P-W, Hu M-H, Hu M-k, Muramatsu S, Ichinose H, Hwu W-L
    • Journal Title

      Neurobiol Dis

      Volume: 52 Pages: 177-190

    • DOI

      10.1016/j.nbd.2012.12.005

    • Peer Reviewed
  • [Journal Article] Intrastriatal gene delivery of GDNF persisitently attenuates methamphetamine self-administration and relapse in mice2013

    • Author(s)
      Yan Y, Miyamoto Y, Nitta A, Muramatsu S, Ozawa K, Yamada K, Nabeshima T
    • Journal Title

      Int JNP

      Volume: 16 Pages: 1559-1567

    • DOI

      10.1017/S1461145712001575

    • Peer Reviewed
  • [Journal Article] Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice.2013

    • Author(s)
      Iwata N, Sekiguchi M, Hattori Y, Takahashi A, Asai M, Ji B, Higuchi M, Staufenbiel M, Muramatsu S, Saido TC
    • Journal Title

      Sci Rep

      Volume: 3 Pages: 1472

    • DOI

      10.1038/srep01472

    • Peer Reviewed
  • [Journal Article] Systemic delivery of tyrosine-mutant AAV vectors results in robust transduction of neurons in adult mice.2013

    • Author(s)
      Iida A, Takino N, Miyauchi H, Shimazaki K, Muramatsu S
    • Journal Title

      Bio Med Res Int

      Volume: 2013 Pages: 974819

    • DOI

      10.1155/2013/974819

    • Peer Reviewed
  • [Journal Article] AADC deficiency: occurring in humans, modeled in rodents.2013

    • Author(s)
      Hwu WL, Lee NC, Chien YH, Muramatsu S, Ichinose H
    • Journal Title

      Adv Pharmacol

      Volume: 68 Pages: 273-284

    • DOI

      10.1016/B978-0-12-411512-5.00013-0

    • Peer Reviewed
  • [Presentation] Gene therapy clinical trial update for AADC.

    • Author(s)
      Muramatsu S
    • Organizer
      Cell and Gene Therapies for Inherited Metabolic Disease
    • Place of Presentation
      London
    • Invited
  • [Presentation] パーキンソン病のAADC遺伝子治療:長期効果遺伝子発現の検証.

    • Author(s)
      村松慎一
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
  • [Presentation] Gene therapy for Parkinson’s disease: Advances and challenges.

    • Author(s)
      Muramatsu S
    • Organizer
      The 36th Annual Meeting of Japan Neuroscience Society
    • Place of Presentation
      京都
  • [Presentation] Overexpression of shati/nat8l in the dorsal striatum affects emotional behaviors via dysfunction of serotonergic neuronal system in mice.

    • Author(s)
      Miyamoto Y, Iegaki N, Sumi K, Ishikawa Y, Furuta T, Hibi Y, Muramatsu S, Nabeshima T, Uno K, Nitta A
    • Organizer
      The 36th Annual Meeting of Japan Neuroscience Society
    • Place of Presentation
      京都
  • [Presentation] Widespread transduction of neurons in the primate brain using intrathecal injection of AAV vectors.

    • Author(s)
      Iida A, Takino N, Miyauchi H, Shibata H, Ono F, Muramatsu S
    • Organizer
      The 36th Annual Meeting of Japan Neuroscience Society
    • Place of Presentation
      京都
  • [Presentation] Distinct regulation mechanism of the dopamine content in the striatum from that in the midbrain.

    • Author(s)
      Iwashita Y, Tokuoka H, Munezane H, Muramatsu S, Ichinose H
    • Organizer
      The 36th Annual Meeting of Japan Neuroscience Society
    • Place of Presentation
      京都
  • [Presentation] Different effects of shati/nat8l-overexpression on the responses to methamphetamine between in mice nucleus accumbens and dorsal striatum.

    • Author(s)
      Nitta A, Ishikawa Y, Iegaki Y, Sumi K, Hurukawa-Hibi Y, Muramatsu S, Nabeshima T, Uno K, Miyamoto Y
    • Organizer
      The 36th Annual Meeting of Japan Neuroscience Society
    • Place of Presentation
      京都
  • [Presentation] Widespread neuronal transduction in the primate brain via intrathecal administration of adeno-associated virus vectors.

    • Author(s)
      Iida A, Takino N, Miyauchi H, Shibata H, Ono F, Muramatsu S
    • Organizer
      The 19th Annual Meeting of the Japan Society of Gene Therapy
    • Place of Presentation
      岡山
  • [Presentation] Global and effective gene delinery of neprilysin to the brain via intravascular administration of AAV vector in alzheimer’s disease mice.

    • Author(s)
      Iwata N, Sekiguchi M, Hattori Y, Takahashi A, Asai M, Ji B, Higuchi M, Muramatsu S, Saido TC
    • Organizer
      The 19th Annual Meeting of the Japan Society of Gene Therapy
    • Place of Presentation
      岡山
  • [Presentation] 多系統萎縮症(NSA-P)のFMT-PET解析.

    • Author(s)
      小野さやか, 藤本健一, 池口邦彦, 村松慎一, 中野今治
    • Organizer
      Movement Disorder Society Japan第7回学術集会
    • Place of Presentation
      東京
  • [Presentation] Parkinson病に対する遺伝子治療の現状と課題.

    • Author(s)
      村松慎一
    • Organizer
      第53回日本定位・機能神経外科学会 シンポジウム
    • Place of Presentation
      大阪
  • [Book] Cell therapy for Parkinson's disease. Clinical implications of fetal transplantation in Medicine.2013

    • Author(s)
      Kondo Y, Okuno T, Asari S, Muramatsu S
    • Total Pages
      11
    • Publisher
      Springer-Verlag
  • [Book] パーキンソン病の遺伝子治療・細胞移植, アクチュアル 脳・神経疾患の臨床 パーキンソン病と運動異常2013

    • Author(s)
      村松慎一
    • Total Pages
      8
    • Publisher
      中山書店

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Published: 2015-05-28  

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