Clinical and genetic analysis on neurodegenerative disorders

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Hokkaido 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
• 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

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.

Research Products

• [Journal Article] Writing errors in ALS related to loss of neuronal integrity in the anterior cingulate gyrus (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Genetic analysis of two Japanese families with progressive external ophthalmoplegia and parkinsonism (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Estimation of skeletal muscle energy metabolism in Machado-Joseph disease using 31P-MR spectroscopy (2011)
  • 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
  • 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
• [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