Development of novel medicine using iPS cells derived from Gaucher disease type II patients

• Project/Area Number: 17K10054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kumamoto University
• Principal Investigator: Kido Jun 熊本大学, 大学院生命科学研究部(医), 助教 (70721215)
• Co-Investigator(Kenkyū-buntansha): 中村 公俊 熊本大学, 大学院生命科学研究部(医), 教授 (30336234) ; 沼川 忠広 熊本大学, 発生医学研究所, 特定事業研究員 (40425690) ; 松本 志郎 熊本大学, 大学院生命科学研究部(医), 准教授 (70467992) ; 曽我 美南 熊本大学, 発生医学研究所, 助教 (80768002)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 先天代謝異常症 / ライソーム病 / 神経幹細胞 / IPS細胞 / iPS細胞 / ゴーシェ病 / Neuron / ゴーシェー病 / ニューロン / Neural stem cell / 神経型ゴーシェー病 / GlcSph / LAMP1 / Gaucher disease / 治療薬開発

Outline of Final Research Achievements

In this research, the iPS cells were generated from patients with GD type II, and neurons were differentiated from GD type II iPS cells. We compared the function of neurons from iPS cells with GD type II and those of neurons from iPSCs with healthy control. Moreover, we developed the drug screening system using the neural stem cells (NSCs) with GD type II and found out the compound, which can alleviate accumulation of GlcSph, from compounds library (1392 compounds). We presently have been analyzing effectiveness of the identified compound in the neurons from iPSCs with GD type II and the model mouse for GD type II, and investigating mechanisms of the compound.

Academic Significance and Societal Importance of the Research Achievements

この研究結果は、プレシナプス機能異常として、SNAREタンパク質の異常が、ポストシナプス機能異常として、種々のCaイオンチャンネルの異常が考えられ、新たなゴーシェ病II型の表現型を提示するとともに新たな治療ターゲットを示唆するものとなった。また、薬剤スクリーニングによって今回見つけ出した化合物は、この化合物自体の本来の作用機序とは異なる作用機序によってGlcSphを低下させていると考えられ、新たな薬理学的作用機序の提示が期待された。さらに、この化合物は、この疾患の治療薬となる可能性だけでなく、この疾患の神経細胞の新たな治療ターゲットを見出す可能性があることを示唆した。

Research Products

• [Journal Article] Newborn screening for Fabry disease in the western region of Japan. (2020)
  • Author(s): Sawada T, Kido J, Yoshida S, Sugawara K, Momosaki K, Inoue T, Tajima G, Sawada H, Mastumoto S, Endo F, Hirose S, Nakamura K.
  • Journal Title: Mol Genet Metab Rep. Volume: 22 Pages: 100562-100562
  • DOI: 10.1016/j.ymgmr.2019.100562
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rhabdomyolysis in organic acidemia patients manifesting with metabolic decompensation. (2019)
  • Author(s): Kido J, Matsumoto S, Sawada T, Endo F, Nakamura K.
  • Journal Title: Hemodial Int. Volume: 23 Issue: 4
  • DOI: 10.1111/hdi.12778
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity. (2019)
  • Author(s): Suzuki Y, Kido J, Matsumoto S, Shimizu K, Nakamura K.
  • Journal Title: BMC Pediatr. Volume: 19 Issue: 1 Pages: 273-273
  • DOI: 10.1186/s12887-019-1647-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients. (2019)
  • Author(s): Momosaki K, Kido J, Yoshida S, Sugawara K, Miyamoto T, Inoue T, Okumiya T, Matsumoto S, Endo F, Hirose S, Nakamura K.
  • Journal Title: J Hum Genet. Volume: 64 Issue: 8 Pages: 741-755
  • DOI: 10.1038/s10038-019-0603-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High-risk screening for Gaucher disease in patients with neurological symptoms. (2018)
  • Author(s): Momosaki K, Kido J, Matsumoto S, Yoshida S, Takei A, Miyabayashi T, Sugawara K, Endo F, Nakamura K.
  • Journal Title: J Hum Genet. Volume: 63 Issue: 6 Pages: 717-721
  • DOI: 10.1038/s10038-018-0438-7
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Development of drug screening system using neural stem cells derived from a patient with Type II Gaucher Disease. (2019)
  • Author(s): Jun Kido, Tadahiro Numakawa, Shirou Matsumoto, Haruki Odaka, Minami Soga, Ryutarou Kajihara, Fumio Endo, Kimitoshi Nakamura, Takumi Era.
  • Organizer: SSIEM annual symposium 2019
  • Int'l Joint Research
• [Presentation] Development of drug screening system using iPS cells derived from a patient with Gaucher Disease Type II (2017)
  • Author(s): Jun Kido, Tadahiro Numakawa, Shirou Matsumoto, Hiroki Odaka, Minami Soga, Ryutarou Kajihara, Fumio Endo, Kimitoshi Nakamura,Takumi Era.
  • Organizer: The 59th Annual Meeting of the Japanese Society for Inherited Metabolic Diseases