Gene Therapy for Fabry disease: development of a miniature swine model

• Project/Area Number: 22590303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kagoshima University
• Principal Investigator: TAKENAKA Toshihiro 鹿児島大学, 大学院・医歯学総合研究科, 特任准教授 (70363645)
• Co-Investigator(Kenkyū-buntansha): HIGUCHI Koji 鹿児島大学, 大学院・医歯学総合研究科, 特任助教 (90448580) ; YOSHIMITSU Makoto 鹿児島大学, 大学院・医歯学総合研究科, 特任助教 (70404530)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 遺伝子治療 / 心 Fabry 病 / Fabry 病 / ミニブタ / 造血幹細胞 / Fabry病 / 心Fabry病

Research Abstract

The aim of this study is to develop a miniature swine model forgene therapy for Fabry disease. We tried to collect hematopoietic stem cells from bonemarrow or G-CSF mobilized peripheral blood mononuclear cells, however G-CSF mobilized apherisis method only allowed us to collect enough number of peripheral blood mononuclear cells. We also tried to establish mouse anti-miniature swine CD34 peptide antibody, however the cells recognized by the antibody did not grow in cytokine containing methlycellulose plate. Further characterization of miniature swine hematopoietic stem cell need to be clarified for utilizing this model in gene therapy preclinical mode.

Research Products

• [Journal Article] Lentivector transduction improves outcomes over transplantation of human HSCs alone in NOD/SCID/Fabry mice (2012)
  • Author(s): Pacienza N, Yoshimitsu M, Mizue N, Au BCY, Wang JCM, Fan X, Takenaka T, Medin JA
  • Journal Title: Molecular Therapy Volume: 20 Pages: 1454-1461
  • Peer Reviewed
• [Journal Article] Sequencing and characterization of the porcine alpha-galactosidase A gene: towards the generation of a porcine model for Fabry disease (2011)
  • Author(s): Yoshimitsu M, Higuchi K, Fan X, Takao S, Medin JA, Tei C, Takenaka T
  • Journal Title: Mol Biol Rep Volume: 38 Pages: 3145-3152
  • Peer Reviewed
• [Journal Article] Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: Pitfalls of mutation analyses in patients with low α-galactosidase A activity (2011)
  • Author(s): Yoshimitsu M, Higuchi K, Miyata M, Devine S, Mattman A, Sirrs S, Medin JA, Tei C, Takenaka T
  • Journal Title: Journal of Cardiology Volume: 57 Pages: 345-353
  • Peer Reviewed
• [Journal Article] Sequencing and characterization of the porcine α-galactosidase A gene : Towards the generation of a porcine model for Fabry disease (2011)
  • Author(s): Yoshimitsu M, et al
  • Journal Title: Molecular Biology Reports Volume: 38 Issue: 5 Pages: 3145-3152
  • DOI: 10.1007/s11033-010-9985-5
  • Peer Reviewed
• [Journal Article] Alpha-galactosidase A-Tat fusion enhances storage reduction in hearts and kidneys of fabry mice (2010)
  • Author(s): Higuchi K, Yoshimitsu M, Fan X, Guo X, Rasaiah VI, Yen J, Tei C, Takenaka T
  • Journal Title: Molecular Medicine Volume: 16 Pages: 216-221
  • Peer Reviewed