Drug development using iPS cells derived from the dental pulp of the patients with neurodegenerative diseases, and metallothionein

• Project/Area Number: 24590664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: HOZUMI Isao 岐阜薬科大学, 薬学部, 教授 (20242430)
• Co-Investigator(Kenkyū-buntansha): INUZUKA Takashi 岐阜大学, 大学院医学系研究科神経内科老年学分野, 教授 (50184734) ; KUNISADA Takahiro 岐阜大学, 大学院医学系研究科組織・器官形成分野, 教授 (30255108) ; 國貞 隆弘 岐阜大学, 医学(系)研究科(研究院), 教授 (30205108)
• Co-Investigator(Renkei-kenkyūsha): AKUTSU Hidenori 独立行政法人国立成育医療研究センター, 室長 (50347225)
• Research Collaborator: KANEKO Masayuki ; INDEN Masatoshi ; NOGUCHI Takao ; ONO Hiroshi ; IKEGAMI Saori ; IRIYAMA Masaki ; KUDO Daichi ; IWASHITA Wakana
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 神経変性疾患 / iPS細胞 / メタロチオネイン / 筋萎縮性側索硬化症 / 分化誘導 / 創薬

Outline of Final Research Achievements

We have been producing iPS cells from dentate pulp in the wisdom teeth and blood cells. We have been planning to treat amyotrophic lateral sclerosis (ALS)-model dogs with dental pulp stem cells. Metallothionine (MT) is a zinc- modulating protein and play important roles in the progression of ALS. In this study we have investigated also a zinc-modulating transporters ZnT families and found the decrease of ZnT-3 and ZnT-6, in particular in the spinal cords of the patients with ALS. This indicates that MT, ZnT-3 and ZnT-6 play pivotal roles in ALS. We have been revealing the roles of these proteins in ALS using iPS cells derived from ALS patients.

Research Products

• [Journal Article] Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis (2015)
  • Author(s): Kaneko M, Noguchi T, Ikegami S, Sakurai T, Kakita A, Toyoshima Y, Kambe T, Yamada M, Inden M, Hara H, Oyanagi K, Inuzuka T, Takahashi H, Hozumi I.
  • Journal Title: J Neurosci Res Volume: 93(2) Issue: 2 Pages: 370-9
  • DOI: 10.1002/jnr.23491
  • NAID: 120007100194
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Conditioned medium of dental pulp cells stimulated by Chinese propolis show neuroprotection and neurite extension in vitro (2015)
  • Author(s): Kudo D, Inden M, Sekine S, Tamaoki N, Iida K, Naito E, Watanabe K, Kamishina H, Shibata T, Hozumi I.
  • Journal Title: Neurosci Lett Volume: 589 Pages: 92-97
  • DOI: 10.1016/j.neulet.2015.01.035
  • Peer Reviewed / Open Access
• [Journal Article] SA4503, a sigma-1 receptor agonist, suppresses motor neuron damage in vitro and in vivo amyotrophic lateral sclerosis models (2014)
  • Author(s): Ono Y, Tanaka H, Takata M, Nagahara Y, Noda Y, Tsuruma K, Shimazawa M, Hozumi I, Hara H.
  • Journal Title: Neurosci Lett Volume: 559 Pages: 174-8
  • DOI: 10.1016/j.neulet.2013.12.005
  • Peer Reviewed
• [Journal Article] Roles and therapeutic potential of metallothionein in neurogenerative diseases (2013)
  • Author(s): Isao Hozmi
  • Journal Title: Current Pharmaceutical Biotechnology Volume: 14 Pages: 408-413
  • Peer Reviewed
• [Presentation] 筋萎縮性側索硬化症（ALS）患者脊髄における亜鉛トランスポーターZnTの発現量低下 (2014)
  • Author(s): 金子雅幸,野口貴生,池上沙織,櫻井丈之,位田雅俊,神戸大朋,柿田明美,豊島靖子,山田光則,原 英彰,高橋 均,保住 功
  • Organizer: 第134回日本薬学会年会
  • Place of Presentation: 熊本大学
• [Presentation] 筋萎縮性側索硬化症（ALS）患者脊髄における亜鉛トランスポーターZnTの発現量低下 (2013)
  • Author(s): 池上沙織，金子雅幸，野口貴生，位田雅俊，柿田明美，豊島靖子，山田光則，高橋 均，保住 功
  • Organizer: メタルバイオサイエンス研究会2013
  • Place of Presentation: 静岡県立大学
• [Presentation] 萎縮性側索硬化症（ALS）患者脊髄における亜鉛トランスポーターZnT3の発現量低下
  • Author(s): 野口貴生，金子雅幸，池上沙織，位田雅俊，柿田明美，豊島靖子，山田光則，高橋 均，保住 功
  • Organizer: 第59回日本薬学会東海支部総会・大会
  • Place of Presentation: 名城大学薬学部
• [Remarks] 岐阜薬科大学医療薬剤学大講座薬物治療学研究室
  • URL: http://www.gifu-pu.ac.jp/lab/yakuchi/Med_Mol_Therp/Home.html
• [Remarks] 岐阜薬科大学医療薬剤学大講座薬物治療学研究室
  • URL: http://www.gifu-pu.ac.jp/lab/yakuchi/Med_Mol_Therp/Home.html