Establish of gene repair methods and analysis of pathological conditions using iPS cells derived from patients with glycogen storage disease type Ia

• Project/Area Number: 26870544
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; Pediatrics
• Research Institution: Kumamoto University
• Principal Investigator: Kido Jun 熊本大学, 医学部附属病院, 診療助手 (70721215)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 糖原病Ia型 / iPS細胞 / 肝臓 / 肝臓分化 / グリコーゲン / 糖原病 / 疾患iPS細胞 / 遺伝子修復

Outline of Final Research Achievements

Glycogen storege disease type Ia (GSD Ia) develop accumulation of glycogen in liver and hypoglycemia by impaired glyconeogenesis because of defect of Glucose-6-Phosphatase (G6Pase) in endoplasmic reticulum. In this study, we developed each iPS cell line with mutation of G6Pase gene from two patients with GSD Ia. Then, we induced iPS cells derived form normal subject and patients with GSD Ia into differentiated hepatocyte. The autophagy in hepatocyte from patients with GSD Ia more enhanced compared to that of hepatocyte from normal subject. Moreover, the autophagy in hepatocyte from patients with GSD Ia increasingly upregulated under low-glucose culture.

Research Products

• [Journal Article] Hyperammonemia crisis following parturition in a female patient with ornithine transcarbamylasedeficiency. (2017)
  • Author(s): Kido J, Kawasaki T, Mitsubuchi H, Kamohara H, Ohba T, Matsumoto F, Endo F, Nakamura K.
  • Journal Title: World J Hepatol. Volume: 9(6) Issue: 6 Pages: 343-348
  • DOI: 10.4254/wjh.v9.i6.343
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pulmonary artery hypertension in methylmalonic acidemia. (2017)
  • Author(s): Kido J, Mitsubuchi H, Sakanashi M, Matsubara J, Matsumoto S, Sakamoto R, Endo F, Nakamura K.
  • Journal Title: Hemodial Int. Volume: Apr;21(2) Issue: 2
  • DOI: 10.1111/hdi.12506
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasma exchange and chelator therapy rescues acute liver failure in Wilson disease without liver transplantation. (2017)
  • Author(s): Kido J, Matsumoto S, Momosaki K, Sakamoto R, Mitsubuchi H, Inomata Y, Endo F, Nakamura K
  • Journal Title: Hepatol Res. Volume: Mar;47(4) Issue: 4 Pages: 359-363
  • DOI: 10.1111/hepr.12711
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evaluation of the skin-prick test for predicting the outgrowth of cow's milk allergy. (2016)
  • Author(s): Kido J, Hirata M, Ueno H, Nishi N, Mochinaga M, Ueno Y, Yanai M, Johno M, Matsumoto T.
  • Journal Title: Allergy Rhinol (Providence) Volume: Jan 1;7(3) Issue: 3 Pages: 139-143
  • DOI: 10.2500/ar.2016.7.0175
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Advanced Endometrial Cancer in Phenylketonuria (2016)
  • Author(s): Jun Kido, Hiroshi Mitsubuchi, Fumiko Itoh, Takanobu Yoshida, Shirou Matsumoto, Rieko Sakamoto, Fumio Endo, Kimitoshi Nakamura
  • Journal Title: Med Sci Case Rep Volume: 3 Pages: 108-111
  • DOI: 10.12659/mscr.901499
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Plasma exchange and chelator therapy rescues acute liver failure in Wilson disease without liver transplantation (2016)
  • Author(s): Jun Kido, Shirou Matsumoto, Ken Momosaki, Rieko Sakamoto, Hiroshi Mitsubuchi,
  • Organizer: 第58回日本先天代謝異常学会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] Improved neurodevelopmental outcomes in patients with urea cycle disorders after liver transplantation. (2016)
  • Author(s): Kido Jun
  • Organizer: Society for the study of inborn errors of metabolism
  • Place of Presentation: ローマ
  • Year and Date: 2016-09-06
  • Int'l Joint Research