Analysis of the phenotype of spinal muscular atrophy based on pre-mRNA regulation

• Project/Area Number: 17K10089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: Arakawa Masayuki 公益財団法人微生物化学研究会, 微生物化学研究所, 上級研究員 (90398868)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脊髄性筋萎縮症 / 運動神経細胞 / SMN蛋白質 / 神経幹細胞 / mRNA前駆体 / スプライシング / 転写

Outline of Final Research Achievements

Spinal muscular atrophy (SMA) is caused by the reduction of survival motor neuron (SMN) protein from the SMN1 gene variations. In this study, we analyzed the exhaustive gene expression of two SMA patients-derived fibroblasts with the different amount of the SMN protein expression. Moreover, we discuss the phenotype of the motor neuron cells from human spinal-derived neural stem cells and the reduction of SMN protein expression.

Academic Significance and Societal Importance of the Research Achievements

脊髄性筋萎縮症(SMA)は原因遺伝子SMN1の変異による常染色体劣性遺伝性疾患であり、脊髄前角細胞の変性による筋萎縮と進行性筋力低下を特徴とする下位運動ニューロン病である。近年、本疾患は新規な治療法が開発され注目を浴びている。本研究では、SMN1変異によるSMN蛋白質の発現減少から生じるSMAの病態を分子細胞生物学に解析することによって、個別化医療への学術的な意義と社会的意義に貢献するものである。

Research Products

• [Journal Article] 1α, 25(OH)2D3 regulates agrin-induced acetylcholine receptor clustering through upregulation of rapsyn expression in C2C12 myotubes (2020)
  • Author(s): Masayuki Arakawa, Akira Wagatsuma
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 525 Issue: 1 Pages: 80-86
  • DOI: 10.1016/j.bbrc.2020.02.027
  • Peer Reviewed
• [Journal Article] Natural products regulate again-induced acetylcholine receptor clustering (2020)
  • Author(s): Masayuki Arakawa, Akira Wagatsuma
  • Journal Title: European Journal of Translational Myology Volume: 30 Issue: 1 Pages: 7-8
  • DOI: 10.4081/ejtm.2019.8966
  • Peer Reviewed / Open Access
• [Presentation] Detection of SMN protein from peripheral human blood and fibroblasts as a biomarker for spinal muscular atrophy (2020)
  • Author(s): Reiko Arakawa, Noriko Otsuki, Masayuki Arakawa, Kayoko Saito
  • Organizer: 2020 PaduaMuscleDays
  • Int'l Joint Research
• [Presentation] 活性型ビタミンDのagrin誘導性アセチルコリンレセプター凝集に対する役割 (2019)
  • Author(s): 荒川正行、我妻玲
  • Organizer: 第５回日本筋学会学術集会
• [Presentation] カルシトリオールはアグリン誘導性にニコチン性アセチルコリン受容体のクラスター化を促進する (2019)
  • Author(s): 我妻玲、松本葉奈乃、荒川正行
  • Organizer: 日本スポーツ栄養学会第６回大会
• [Presentation] イメージングFCMを用いた脊髄性筋萎縮症に対する新規バイオマーカーの開発 (2019)
  • Author(s): 前川貴則、大月典子、今久保桃子、山本毅、山田和弘、荒川玲子、荒川正行、斎藤加代子
  • Organizer: 日本薬学会139年会
• [Presentation] Natural products can modulate again-induced acetylcholine receptors clustering (2019)
  • Author(s): Masayuki Arakawa, Akira Wagatsuma
  • Organizer: 2019 Muscle Biology Conference University of Florida
  • Int'l Joint Research
• [Presentation] Evaluation method of survival motor neuron protein as a biomarker for spinal muscular atrophy patient based on imaging flow cytometry (2019)
  • Author(s): Reiko Arakawa, Noriko Otsuki, Kaori Kaneko, Masayuki Arakawa, Kayoko Saito
  • Organizer: 2019 Muscle Biology Conference University of Frorida
  • Int'l Joint Research
• [Presentation] イメージングフローサイトメーターを用いた脊髄性筋萎縮症に対する新規バイオマーカーの開発 (2018)
  • Author(s): 前川貴則、大月典子、今久保桃子、山本毅、山田和弘、荒川玲子、荒川正行、斎藤加代子
  • Organizer: 第3回 日本遺伝子細胞治療学会若手セミナー
• [Presentation] 脊髄性筋萎縮症(SMA)のバイオマーカー：末梢血を用いたSMN蛋白質新規開発法の提案 (2018)
  • Author(s): 大月典子、荒川玲子、金子芳、青木亮子、荒川正行、斎藤加代子
  • Organizer: 第25回日本遺伝子診療学会
• [Presentation] A novel approach to SMN protein-based evaluation as biomarker in spinal muscular atrophy (2017)
  • Author(s): Masayuki Arakawa , Reiko Arakawa , Kayoko Saito
  • Organizer: 6th International Conference on Neurology and Neuromuscular Diseases
  • Int'l Joint Research
• [Presentation] Imaging flow cytometry for identifying differences in SMN protein expression between spinal muscular atrophy patients and normal subjects (2017)
  • Author(s): Reiko Arakawa ,Masayuki Arakawa, Kayoko Saito
  • Organizer: 6th International Conference on Neurology and Neuromuscular Diseases
  • Int'l Joint Research
• [Presentation] Method of evaluating survival motor neuron protein as an outocome measure of SMA-modifying therapy (2017)
  • Author(s): Reiko Arakawa , Masayuki Arakawa ,Noriko Otski, Kaori Kaneko , Ryoko Aoki , Kayoko Saito
  • Organizer: 第14回アジア大洋州小児神経学会
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] SMNタンパク質の核内構造体の発現解析方法 (2018)
  • Inventor(s): 斎藤加代子、荒川玲子、荒川正行
  • Industrial Property Rights Holder: 斎藤加代子、荒川玲子、荒川正行
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Acquisition Date: 2020