Analysis of SMN protein complex in spinal muscular atrophy patients-derived cells.

• Project/Area Number: 17K16281
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Arakawa Reiko 東京女子医科大学, 医学部, 非常勤講師 (40623111)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脊髄性筋萎縮症 / SMNタンパク質 / イメージングフローサイトメトリー

Outline of Final Research Achievements

Spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron 1 (SMN1) gene. These mutations result in reduced expression of survival motor neuron (SMN) protein and SMN complex. Here, we report a method that allows the evaluation of SMN protein in <1.5 ml of peripheral blood using imaging flow cytometry. This technique successfully identified different expression patterns and subcellular localization of SMN protein in healthy human and SMA patient-derived cells.

Academic Significance and Societal Importance of the Research Achievements

全身性の筋萎縮を生じる遺伝性疾患である脊髄性筋萎縮症に対しては、アンチセンスオリゴヌクレオチド製剤や、SMN1遺伝子の機能欠損を補う遺伝子治療法ベクター製品が承認されている。本研究で構築した、1.5mlの血液で解析可能なSMNタンパク質定量手法は、これらの治療の効果を客観的に評価するバイオマーカーの基礎研究となり、将来的に治療の適正化に貢献するものと考えられる。

Research Products

• [Journal Article] Detection of SMN protein from peripheral human blood and fibroblasts as a biomarker for spinal muscular atrophy. (2020)
  • Author(s): Arakawa R, Otsuki N, Arakawa M, Saito K.
  • Journal Title: European Journal of Translational Myology Volume: 30 Pages: 37-37
• [Journal Article] A new biomarker candidate for spinal muscular atrophy: Identification of a peripheral blood cell population capable of monitoring the level of survival motor neuron protein (2018)
  • Author(s): Otsuki Noriko、Arakawa Reiko、Kaneko Kaori、Aoki Ryoko、Arakawa Masayuki、Saito Kayoko
  • Journal Title: PLOS ONE Volume: 13 Issue: 8 Pages: e0201764-e0201764
  • DOI: 10.1371/journal.pone.0201764
  • Peer Reviewed / Open Access
• [Journal Article] Relationships between long-term observations of motor milestones and genotype analysis results in childhood-onset Japanese spinal muscular atrophy patients (2017)
  • Author(s): Kaneko K, Arakawa R, Urano M, Aoki R, Saito K
  • Journal Title: Brain Dev. Volume: 39 Issue: 9 Pages: 763-773
  • DOI: 10.1016/j.braindev.2017.04.018
  • Peer Reviewed
• [Presentation] Evaluation method of survival motor neuron protein as a biomarker for spinal muscular atrophy patient based on imaging flow cytometry (2018)
  • Author(s): Reiko Arakawa, Noriko Ostuki, Kaori Kaneko,Masayuki Arakawa Kayoko Saito
  • Organizer: Advances in skeletal muscle biology in health and disease conference
  • 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、山田和宏、荒川玲子、荒川正行、斎藤加代子
  • Organizer: 日本薬学会第139年会
• [Presentation] 脊髄性筋萎縮症のバイオマーカー：末梢血を用いたSMN蛋白質新規解析法の提案および精度向上に向けての改良 (2018)
  • Author(s): 大月典子、前川貴則、荒川玲子、山田和宏、斎藤加代子
  • Organizer: 日本人類遺学会第63回大会
• [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蛋白質新規解析法の提案 (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] Method of evaluating survival motor neuron protein as an outcome measure of SMA-modifying therapy (2017)
  • Author(s): Arakawa R,Arakawa M,Otsuki N,Kaneko K,Aoki R, Saito K
  • Organizer: 14th Asian and Oceanian Congress of Child Neurology
  • 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): Arakawa R,Arakawa M,Saito K
  • Organizer: 6th International Conference on Neurology and Neuromuscular diseases
  • Int'l Joint Research / Invited
• [Presentation] A novel approach to SMN protein-based evaluation as biomarker in spinal muscular atrophy (2017)
  • Author(s): Arakawa M,Arakawa R,Saito K
  • Organizer: 6th International Conference on Neurology and Neuromuscular diseases
  • Int'l Joint Research / Invited
• [Presentation] 脊髄性筋萎縮症Ⅰ型患者由来リンパ芽球におけるSMN蛋白発現量の解析 (2017)
  • Author(s): 荒川玲子、金子芳、荒川正行、浦野真理、青木亮子、斎藤加代子
  • Organizer: 日本人類遺伝学会第62回大会
• [Presentation] 脊髄性筋萎縮症におけるSMN1遺伝子の遺伝学的検査と遺伝カウンセリング (2017)
  • Author(s): 荒川玲子、久保祐二、金子芳、浦野真理、青木亮子、伊藤万由里、斎藤加代子
  • Organizer: 第４１回日本遺伝カウンセリング学会学術集会