Development of biomarker and therapy for amyotrophic lateral sclerosis targeting cystatin C

• Project/Area Number: 15K15337
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Katsuno Masahisa 名古屋大学, 医学(系)研究科(研究院), 教授 (50402566)
• Co-Investigator(Kenkyū-buntansha): Sahashi Kentaro 名古屋大学, 医学部附属病院, 医員 (90710103) ; KONDO Naohide 名古屋大学, 医学部附属病院, 医員 (20725527)
• Co-Investigator(Renkei-kenkyūsha): Sobue Gen 名古屋大学, 大学院医学系研究科, 特任教授 (20148315) ; Okada Yohei 愛知医科大学, 医学部, 准教授 (30383714)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 運動ニューロン疾患 / シスタチンC / バイオマーカー / 筋萎縮性側索硬化症 / 呼吸機能

Outline of Final Research Achievements

We investigated the serum levels of cystatin C in the subjects with sporadic ALS, both cross-sectionally and longitudinally, to clarify whether serum cystatin C is a potential biomarker reflecting the severity of motor dysfunction and predicting prognosis of this disease. The results were compared with those with healthy controls (HC) and spinal and bulbar muscular atrophy (SBMA). Baseline levels of serum cystatin C in the subjects with ALS were significantly higher than those of HC and SBMA. As for the relationship between disease severity, a strong correlation was found between baseline levels of serum cystatin C and ALSFRS-R in the subjects with ALS. Furthermore, baseline levels of serum cystatin C were correlated with the 24-week change of %FVC and that of appendicular lean soft tissue mass, as an index of skeletal muscle mass, in ALS. In conclusion, serum cystatin C may be a potential biomarker which reflects the disease progression of ALS.

Research Products

• [Journal Article] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort (2016)
  • Author(s): Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
  • Journal Title: Neurobiology of Aging Volume: 39 Pages: 219-219
  • DOI: 10.1016/j.neurobiolaging.2015.11.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycoprotein nonmetastatic melanoma protein B ameliorates skeletal muscle lesions in a SOD1G93A mouse model of amyotrophic lateral sclerosis. (2015)
  • Author(s): Nagahara Y, Shimazawa M, Tanaka H, Ono Y, Noda Y, Ohuchi K, Tsuruma K, Katsuno M, Sobue G, Hara H.
  • Journal Title: J Neurosci Res. Volume: 93 Issue: 10 Pages: 1552-1566
  • DOI: 10.1002/jnr.23619
  • Peer Reviewed
• [Journal Article] FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1 mRNA stabilization. (2015)
  • Author(s): Udagawa, T., Fujioka, Y., Tanaka, M., Honda, D., Yokoi, S., Riku, Y., Ibi, D., Nagai, T., Yamada, K., Watanabe, H., Katsuno, M., Inada, T., Ohno, K., Sokabe, M., Okado, H., Ishigaki S*., and Sobue, G.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 7098-7098
  • DOI: 10.1038/ncomms8098
  • Peer Reviewed / Open Access
• [Presentation] Disruped muscle uptake of creatine in spinal and bulbar muscular atrophy (2015)
  • Author(s): Hijikata Y, Katsuno M, Suzuki K, Banno H, Hashizume A, Yamada S, Sobue G.
  • Organizer: The 26th International Symposium on ALS/MND
  • Place of Presentation: Orlando(USA)
  • Year and Date: 2015-12-11
  • Int'l Joint Research
• [Presentation] Impaired muscular creatine metabolism in spinal and bulbar muscular atrophy (SBMA). (2015)
  • Author(s): Hijikata Y, Katsuno M, Suzuki K, Banno H, Hashizume A, Yamada S, Sobue G.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2015-05-20
• [Presentation] 球脊髄性筋萎縮症患者における呼吸 機能－筋萎縮性側索硬化症との比較－ (2015)
  • Author(s): 山田晋一郎、勝野雅央、鈴木啓介、 橋詰淳、土方靖浩、祖父江元
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2015-05-20
• [Presentation] 運動ニューロン疾患の分子病態解明に基づく治療標的開発. (2015)
  • Author(s): 勝野雅央.
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2015-05-20
  • Invited