Developing new therapeutic drugs that inhibit oligomer formation of polyglutamine disease proteins based on the hypothesis of oligomer toxicity in polyglutamine diseases

• Project/Area Number: 25461272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: Tada Masayoshi 新潟大学, 脳研究所, 助教 (10467079)
• Co-Investigator(Kenkyū-buntansha): Onodera Osamu 新潟大学, 脳研究所, 教授 (20303167)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脊髄小脳変性症 / ポリグルタミン病 / 治療 / 重合体 / 臨床評価法 / 小脳性運動失調 / 新規治療法 / 評価法 / 重合体形成 / SCD / ataxia / polyglutamine disease / therapy / oligomer

Outline of Final Research Achievements

We developed new therapeutic drugs that inhibit oligomer formation of polyglutamine disease proteins based on the hypothesis of oligomer toxicity in polyglutamine diseases. Using a disease nematode model, we found a small compound that inhibit oligomer formation of disease proteins and ameliorate motor function of the nematode model. We also developed a novel system using iPad for the quantitative assessment of cerebellar ataxia. In addition, we started a clinical trial to investigate the safety and efficiency of varenicline (Champix), a prescription medication used to treat nicotine addiction, in the treatment of spinocerebellar degenerations.

Research Products

• [Journal Article] 小脳症状をどう捉えるか：小脳機能に基づく小脳症状の再構築 (2016)
  • Author(s): 他田正義, 西澤正豊, 小野寺理
  • Journal Title: MDSJ Letters Volume: 9(1) Pages: 4-5
• [Journal Article] 高齢者における小脳失調症に対する診断アプローチ (2016)
  • Author(s): 高橋茉那, 他田正義, 下畑享良, 西澤正豊
  • Journal Title: Geriat Med Volume: 54 Pages: 217-223
• [Journal Article] Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias. (2016)
  • Author(s): Tada M, Nishizawa M, Onodera O.
  • Journal Title: Neurochem Int. Volume: 94 Pages: 1-8
  • DOI: 10.1016/j.neuint.2016.01.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Redefining cerebellar ataxia in degenerative ataxias: lessons from recent research on cerebellar systems. (2015)
  • Author(s): Tada M, Nishizawa M, Onodera O
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: - Issue: 8 Pages: 922-928
  • DOI: 10.1136/jnnp-2013-307225
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. (2014)
  • Author(s): Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K.
  • Journal Title: Am J Hum Genet Volume: 95(3) Pages: 294-300
  • Peer Reviewed / Open Access
• [Journal Article] Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS): A Review of the Literature on its Clinical Characteristics and Mutations in the Colony-Stimulating Factor-1 Receptor Gene. (2014)
  • Author(s): Konno T, Tada M, Tada M, Nishizawa M, Ikeuchi T.
  • Journal Title: Brain Nerve Volume: 66 Pages: 581-590
  • NAID: 40020089061
• [Journal Article] セナタキシン欠損症 (2014)
  • Author(s): 他田正義，西澤正豊
  • Journal Title: 神経症候群（第2版） Volume: 27 Pages: 389-393
• [Journal Article] Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of Japanese patients with novel SCARB2 mutations (2013)
  • Author(s): Fu YJ, Aida I, Tada M, Tada M, Toyoshima Y, Takeda S, Nakajima T, Naito H, Nishizawa M, Onodera O, Kakita A, and Takahashi H
  • Journal Title: Neuropathol Appl Neurobiol Volume: doi:10.1111/nan.12057. Pages: 12057-12057
  • Peer Reviewed
• [Journal Article] 【小脳の神経学】 治療研究に向けた小脳機能評価法の将来 (2013)
  • Author(s): 徳永純, 他田正義, 永井貴大, 西澤正豊, 小野寺理
  • Journal Title: 神経内科 Volume: 78 Pages: 687-694
• [Presentation] 小脳症状をどう捉えるか：小脳機能に基づく小脳症状の再構築 (2015)
  • Author(s): 他田正義, 小野寺理, 西澤正豊
  • Organizer: 第9回パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 品川プリンスホテル（東京都品川区）
  • Year and Date: 2015-10-15
  • Invited
• [Presentation] Kinect を用いた3次元歩行解析システムによる小脳性歩行障害の解析 (2015)
  • Author(s): 他田正義, 徳永純, 小野寺理, 西澤正豊
  • 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] SCARB2変異を認めた進行性ミオクローヌスてんかん 2剖検例の臨床病理・生化学的解析． (2014)
  • Author(s): 他田正義，付永娟，会田泉，他田真理，武田茂樹，豊島靖子，中島孝，内藤明彦，高橋均，小野寺理，西澤正豊．
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21
• [Presentation] iPatax：小脳性運動失調の新たな定量評価法． (2014)
  • Author(s): 徳永純，他田正義，永井貴大，小野寺理，西澤正豊．
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-05-21
• [Presentation] iPatax: A new method for quantitative assessment for motor coordination of ataxia. (2014)
  • Author(s): Tada M, Tokunaga J, Nagai T, Nishizawa M, Onodera O.
  • Organizer: AAN Annual Meeting 2014
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2014-05-01
• [Presentation] 等速直線運動の速度変動に着手した小脳性運動失調の新たな定量評価法 (2013)
  • Author(s): 徳永純，他田正義，永井貴大，小野寺理，西澤正豊
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Book] Pathologies of calcium channels; Chapter 28, IP3 Receptors in Neurodegenerative Disorders: Spinocerebellar Ataxias and Huntington’s and Alzheimer’s Diseases (2014)
  • Author(s): Tada M, Nishizawa M, and Onodera O
  • Publisher: Springer