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Treatment for congenital metabolic disorder with brain dysfunction.

Research Project

Project/Area Number 11670791
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionThe Jikei University School of Medicine

Principal Investigator

TOKORO Toshiharu  Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (40112841)

Co-Investigator(Kenkyū-buntansha) IDA Hiroyuki  Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (90167255)
OHASHI Touya  Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (60160595)
ONO Tsuneya  Jikei Univ., Dept.of Pediatrics prof., 医学部, 教授 (60147288)
ETO Yoshikatsu  Jikei Univ., Dept.of pediatrics prof., 医学部, 教授 (50056909)
大野 京子  東京慈恵会医科大学, 医学部, 助手 (10301524)
小林 博司  東京慈恵会医科大学, 医学部, 助手 (90266619)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsNeural progenitor / Niemann-Pick Disease TypeC / Adenovirus Vector / Cytkine / アデノウイルスベクター / Niemann-Pick病type C / Nieman-Pick病typeC
Research Abstract

1)Treatment for Niemann-Pick disease by Neural Progenitor Cells ;
We study the transplantation of neural progenitors as a novel strategy gene therapy and repair in neurodegenerative disorders, Niemann-Pick Disease.
Neural progenitor cells (NPC) were injected into left lateral-ventricular space in the 12 Neimann-Pick disease mice model. After 1 month injection of NPC, we found the LacZ activities in brain tissues which is around the lateral-ventricular space and other right side of same area in the brain. But we could not find enough activities of LacZ in vitro. We are now trying to make Neuronal Progenitor Cells which have NPC gene and to injects them into the brain of Niemann-Pick Disease mouse model and its fetus.
2)Blood Brain Barrier disruption by cytokine and injection Adenovirus with LacZ gene into brain ; We tried the disruption of BBB by IL-l & TNF-alfa. We injected Adenovirus intra cervical artery of mouse after injection of 20% of manitor. We found faint LacZ activities in the brain around the brain artery but did not any invitro-activities. Mice sometimes have the convulsion after injection of cytokines. we need more experiments to find out the suitable dosage of cytokines and way of injection.
3)Try to treat for neurogenarative disorder of mouse fetus ; We injected adenovirus vector which has LacZ gene into fetus amniotic vein of mice. We found LacZ activities in the liver tissues cytochemically but no activities in the brain and other tissues. One of our colleague found that some activities in the brain after injection of adenovirus into amniotic fluid of early stage of gestation, the day 3-7.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Eto Y.,Ohashi T.: "Gene therapy/cell therapy for lysosomal storage disease."J Inherited Metabo Dis. 23(3). 293-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watabe K.,Ohashi T.,Eto Y.: "Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor."Journal of Neuroscience Research. 60. 511-9 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ida H,Eto Y.: "Effects of enzyme replacement therapy in 13 Japanese pediatric patients with Gaucher disease."Eur J Pediatr. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T.,Ohashi T.,Eto Y.: "Adenoviral Vector mediated GDNF gene transfer prevents death of adult facial notoneurons."Neuroreport. 11(9). 1857-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuda M,Ida H,Eto Y: "A newly recognized missense mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome."Eur J Pediatr. 159. 867 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohashi T., Iizuka S., Sly W.S., Machiki Y., Eto Y.: "Efficient and persistent expression of β-glucuronidase gene in CD34+cells from human umbilical cord blood by retroviral vector."Eur.J.Haematol. 61(4). 235-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ida H., Rennert OM., Kato S., Ueda T., Oishi K., Maekawa K.and Eto Y.: "Severe skeletal complications in Japanese patients with type l Gaucher disease."J Inher Metab Dis. 22. 63-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eto Y., Ohashi T.: "Gene therapy/cell therapy for lysosomal storage disease."J Inherited Metabo Dis. 23(3). 293-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Futagawa Y., Okamoto T., Ohashi T., Eto Y.: "Efficiency of adenovirus-mediated gene Transfer into hepatocytes by liver asanguineous perfusion method."Res Exp Med (Berl). 199(5). 263-74 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohashi T., Yokoo T., Izuka S., Kobayashi H., Sly W.S.and Eto Y.: "Eduction of Lysosomal storage in Murine Mucoplysaccharidosis Type VII by Transplantation of Normal and Genetically Modified Macrophages."Blood. 95(11). 3631-3 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watabe K., Ohashi T., Sakamoto T., Kawazoe Y., Takeshima T., Oyanagi K., Inoue K., Eto Y., and Kim S.U.: "Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor."Journal of Neuroscience Research. 60. 511-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsujino S., Kanazawa N., Ohashi T., Eto Y., Saito T., Kira.J.: "Three novel mutations (G27E, insAAC, R179X) in the ORNT1 gene of Japanese patients with HHH syndrome."Arch of Neuro. 147(5). 625-31 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T., Watabe K., Ohashi T., Kawazoe Y., Oyanagi K., Inoue K., Eto Y.: "Adenoviral Vector mediated GDNF gene transfer prevents death of adult facial notoneurons."Neuroreport. 11(9). 1857-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Eto Y.,Ohashi T.: "Gene therapy/cell therapy for lysosomal storage disease."J Inherited Metabo Dis. 23(3). 293-8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watabe K.,Ohashi T.,Eto Y.: "Rescue of lesioned adult rat spinal motoneurons by adenoviral gene transfer of glial cell line-derived neurotrophic factor."Journal of Neuroscience Research. 60. 511-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ida H,Eto Y.: "Effects of enzyme replacement therapy in 13 Japanese pediatric patients with Gaucher disease."Eur J Pediatr. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakamoto T.,Ohashi T.,Eto Y.: "Adenoviral Vector mediated GDNF gene transfer prevents death of adult facial notoneurons."Neuroreport. 11(9). 1857-60

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuda M,Ida H,Eto Y: "A newly recognized missense mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome."Eur J Pediatr. 159. 867

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohashi T., Yokoo T., Eto Y., et al.: "Eduction of Lysosomal storage in Murine Mucoplysaccharidosis・・・"Blood. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watabe K., Ohashi T., Eto Y., et al.: "Rescue of lesioned adult rat spinal motoneurons by・・・"Journal of Neuroscience Research. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Eto Y., Ida H.: "Clinical and molecular Characteristics of Japanese Gaucher Disease"Neurochem Res. 24(2). 207-211 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ida H., Rennert OM., Eto Y., et al.: "Clinical and genetic studies of Japanese homozygotes for the・・・"Hum Genet. 105. 120-126 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Oishi K., , Ida H., Eto Y., et al.: "Clinical and molecular of Japanese patients with neuronal・・・"Molecular Genetics and Metabolism. 66. 344-348 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yokoo T., Ohashi T., Eto Y., et al.: "Prophyaxis of Antibody-Induced Acute Glomerulonephritis・・・"Hum Gene Ther. 10. 2673-2678 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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