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Clinical and genetic analysis on neurodegenerative disorders

Research Project

Project/Area Number 21591066
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YABE Ichiro  北海道大学, 大学院・医学研究科, 准教授 (60372273)

Co-Investigator(Renkei-kenkyūsha) SASAKI Hidenao  北海道大学, 大学院・医学研究科, 教授 (80281806)
AKIMOTO Sachiko  北海道大学, 大学院・医学研究科, 助教 (60374328)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脊髄小脳変性症 / PRKCG / Machado-Joseph disease / ^<31>P-MRS / POLG / パーキンソン病 / ミトコンドリア / POLG1 / SCA14 / 筋萎縮性側索硬化症 / PET / 筋エネルギー代謝
Research Abstract

The aim of this study was to determine if muscle energy metabolism, as measured by 31P-magnetic resonance spectroscopy (MRS), is a metabolic marker for the efficacy of treatment of Machado-Joseph disease (MJD). The data showed that there was a significant difference between the groups in terms of the PCr/(Pi + PCr) ratio at rest (p=0.03) and the maximum rate of mitochondrial ATP production (Vmax) (p < 0.01). In addition, Vmax was inversely correlated with the scale for the assessment and rating of ataxia (SARA) score (r=-0.34, p=0.04). The MJD group also showed a reduction in Vmax over the course of two years (p<0.05). These data suggest that non-invasive measurement of muscle energy metabolism may represent a surrogate marker for MJD.
In addition, in order to define the molecular basis of progressive external ophthalmoplegia and parkinsonism, we screened for mutations in PEO1, ANT1, POLG genes and the whole mitochondrial genome in two families. In results, we identified a compound heterozygous POLG substitutions in one of the families. In the other family, no mutations were detected in any of the three genes and the whole mitochondrial genome in the blood sample, although mitochondrial DNA deletions were observed in the muscle biopsy sample. Progressive external ophthalmoplegia and parkinsonism are genetically heterogenous disorders, and part of this syndrome may be caused by mutations in other, unknown genes.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2012 2011 2010 2009 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (6 results)

  • [Journal Article] Writing errors in ALS related to loss of neuronal integrity in the anterior cingulate gyrus2012

    • Author(s)
      Yabe, I., Tsuji-Akimoto, S., Shiga, T., Hamada, S., Hirata, K., Otsuki, M., Kuge, Y., Tamaki, N., Sasaki, H.
    • Journal Title

      J Neurol Sci

      Volume: 315 Pages: 55-59

    • NAID

      120003974403

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Writing errors in ALS related to loss of neurons integrity in the anterior cingulate gyrus2012

    • Author(s)
      Yabe I, et al.
    • Journal Title

      J Neurol Sci

      Volume: 315 Issue: 1-2 Pages: 55-59

    • DOI

      10.1016/j.jns.2011.11.039

    • NAID

      120003974403

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of two Japanese families with progressive external ophthalmoplegia and parkinsonism2011

    • Author(s)
      Kazunori Sato, Ichiro Yabe, Hiroaki Yaguchi, Fumihito Nakano, Yasuyuki Kunieda, Shinji Saitoh, Hidenao Sasaki
    • Journal Title

      J Neurol

      Volume: 258 Pages: 1327-32

    • NAID

      120004405523

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Estimation of skeletal muscle energy metabolism in Machado-Joseph disease using 31P-MR spectroscopy2011

    • Author(s)
      Ichiro Yabe, Khin K. Tha, Takashi Yokota, Kazunori Sato, Hiroyuki Soma, Asako Takei, Satoshi Terae^2, Koichi Okita, Hidenao Sasaki
    • Journal Title

      Mov Disord

      Volume: 26 Pages: 165-8

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Estimation of skeletal muscle energy metabolism in achado-Joseph disease using 31P-MR spectroscopy2011

    • Author(s)
      Yabe I, et al.
    • Journal Title

      Mov Disord

      Volume: 26 Issue: 1 Pages: 165-8

    • DOI

      10.1002/mds.23335

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of two Japanese families with progressive external ophthalmoplegia and Parkinsonism2011

    • Author(s)
      Sato K, Yabe I, et al.
    • Journal Title

      J Neurol

      Volume: 258 Pages: 1327-32

    • NAID

      120004405523

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estimation of skeletal muscle energy metabolism in Machado-Joseph disease using 31P-MR spectroscopy.2011

    • Author(s)
      Yabe I, et al.
    • Journal Title

      Movement Disorders

      Volume: 26 Pages: 165-168

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microstructural white matter abnormalities of multiple system atrophy : in vivo topographic illustration by using diffusion-tensor MR imaging.2010

    • Author(s)
      Tha KK, Yabe I, et al.
    • Journal Title

      Radiology

      Volume: 255 Pages: 563-569

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autosomal dominant cerebellar ataxia without pathogenic PPP2R2B mutation mans to SCA12 locus.2010

    • Author(s)
      Sato K, Yabe I, et al.
    • Journal Title

      Archives of Neurology

      Volume: 67 Pages: 1257-1262

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MERRF/MELAS overlap syndrome : A double pathogenic mutation in mitochondrial tRNA genes.2010

    • Author(s)
      Yabe I, et al.
    • Journal Title

      Journal of Medical Genetics

      Volume: 47 Pages: 659-664

    • NAID

      120002722535

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progressive anterior operculum syndrome due to FTLD-TDP : a clinico-pathological investigation.2010

    • Author(s)
      Otsuki M, Yabe I, et al.
    • Journal Title

      Journal of Neurology

      Volume: 257 Pages: 1148-1153

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新しい小脳性運動失調の重症度評価スケールScale for the Assessment and Rating of Ataxia(SARA)日本語版の信頼性に関する検討2009

    • Author(s)
      佐藤和則
    • Journal Title

      Brain and Nerve 61

      Pages: 591-595

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of two Japanese families with progressive external ophthalmoplegia and parkinsonism.

    • Author(s)
      Sato K, Yabe I, et al.
    • Journal Title

      Journal of Neurology

      Volume: (In press)

    • NAID

      120004405523

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo topographic illustration of microstructural white matter abnormalities of multiple system atrophy by diffusion tensor imaging.

    • Author(s)
      Tha KK
    • Journal Title

      Radiology (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autosomal dominant cerebellar ataxia without pathogenic PPP2R2B mutation maps to SCA12 locus.

    • Author(s)
      Sato K
    • Journal Title

      Archives of Neurology (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MERRF/MELAS overlap syndrome : A double pathogenic mutation in mitochondrial tRNA genes.

    • Author(s)
      Yabe I
    • Journal Title

      Journal of Medical Genetics (In press)

    • NAID

      120002722535

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 進行性外眼筋麻痺を伴ったパーキンソニズムの遺伝子解析2011

    • Author(s)
      佐藤和則、矢口裕章、加納崇裕、矢部一郎、佐木秀直、國枝保幸
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2011-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] 進行性外眼筋麻を伴ったパーキンソニズムの遺伝子解析2011

    • Author(s)
      佐藤和則
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場,愛知
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] ALSにおける11C-フルマゼニル(FMZ)-PET所見2011

    • Author(s)
      矢部一郎、秋本幸子、大槻美佳、志賀哲、玉木長良、佐木秀直
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2011-05-18
    • Related Report
      2011 Final Research Report
  • [Presentation] ALSにおける11C-フルマゼニル(FMZ)-PET所見2011

    • Author(s)
      矢部一郎
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋国際会議場,愛知
    • Year and Date
      2011-05-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] ポリグルタミン病の筋エネルギー代謝2010

    • Author(s)
      矢部一郎
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] ポリグルタミン病の筋エネルギー代謝2009

    • Author(s)
      矢部一郎
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台市国際センター
    • Year and Date
      2009-05-20
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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