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Modified enzyme which target to neuronal cells to cross blood brain barrier

Research Project

Project/Area Number 02557042
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTokyo Jikei University School of Medicine

Principal Investigator

ETO Yoshikatsu  Jikei Univ. Pediatrics assoc. prof., 医学部, 助教授 (50056909)

Co-Investigator(Kenkyū-buntansha) KUSANO Kaoru  Jikei Univ. Pediatrics assistant, 医学部, 助手 (80205070)
SASAKI Nobuhiko  Jikei Univ. Pediatrics assistant, 医学部, 助手 (50170684)
IDA Hiroyuki  Jikei Univ. Pediatrics assistant, 医学部, 助手 (90167255)
TOKORO Toshiharu  Jikei Univ. Pediatrics assistant prof., 医学部, 講師 (40112841)
ITO Fumiyuki  Jikei Univ. Pediatrics assoc. prof., 医学部, 助教授 (10057010)
梅沢 房代  東京慈恵会医科大学, 小児科学, 助手 (50185063)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1991: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsliposome / blood brain barrier / neuronal cell / mannnose terminal / Glucocerebrosidase / リボゾ-ム / グリア細胞 / cerebrosideβ-galactosidase / マンノ-ス / リポゾ-ム / 脳障害 / 酵素補充療法 / α_2ーマクログロブリン / 培養神経細胞 / αーマンノ-ス含有リポゾ-ム
Research Abstract

MODIFIED ENZYME WHICH TARGFRS TO NEURONAL CELLS TO CROSS BLOOD BRAIN BARRIER
We tried to prepare modified placental glucocerebrosidase treated with neuraminidase and galactosidase and mumose terminal glucocerebrosidase was injected intravenously into mouse. We chased enzyme activities of glucocerebrosidase in mouse brain, Ever, kidney and other tissues. The maximum activity of the enzyme was obtkned after 15 minute injection, and significant staining of-enzyme-activity was found in the brain. These data suggest that mamose terminated enyzme could be useful for the treatment of neuronopathic Gaucher disease. Liposomes prepared from lecithincholesterol- aminophenylmwmoside (7 : 2 : 1) were efficiently incorporated into mouse brain across the blood brain barrier. Furthermore, hposomes injected intraperitoneauy were exclussively distributed into lysosome rich fraction and taken up by glial cells. These data suggest that blood brain barrier cells and glial cells recognize mannose and can be used for the treattnent of brain damage by lysosomat storage disease.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Kawame H,Eto Y.: "A New GlucoceevebrosidaseーGene Missense Mutation Responsible tor Neuronopathic Gacher Disease in Japanese Patients." Am.J.Hum.Genet. 49. 1378-1380 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H,Eto Y,Maekawa K.: "Biochemical pathogensis of demyelination in globoid cell leukodystrophy(krabbe's disease)" Acta Padiatr.Jap.32. 20-26 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H,Eto Y.: "Biochemical and Morphological studies of dorsal root ganglion and its cultured from twitcher mouse." Brain and Develop.12. 412-416 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 衛藤 義勝: "ライゾ-ム病の骨髄移殖による治療法の最近の進歩" 小児科診療. 43. 645-651 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H,Eto Y.Maekawa K.: "Fetal GM_1ーgangliosidosis:Morphological and biochemical studies." Brain and Develop.11. 394-398 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 衛藤 義勝: "遺伝子組み変え技術により作製した天然ヒト成長ホルモン製剤、SJー0011の下垂体性小人症に対する臨床試験" 薬理と治療. 17. 465-486 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 衛藤 義勝,永津俊治他編: "脳と遺伝子" 平凡社, 11 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 衛藤 義勝,中村 治雄他編: "脂質の科学" 朝倉書店, 18 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Ohashi, Y. Eto: "Molecular analysis of Japanese Gaucher Disease" J. Intherited Dis.12. 355-358 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Eto, F. Umezawa: "Iposomal therapy in lysosomal storage disease." Amer. J. Med. Genet.7. 85-88 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H., Eto Y. and Maekawa K. Fetal: "GM1-gangliosidosis ; Morpholosocal and biochemical studies." Brain and Develop.11. 394-398 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Matsuki K., Shirasawa N. and Eto Y. Cytoplasimic accumulations in rat primary brin cell culture foll: "owing treatment with 64, a thiol protease inhibitors." Developmental Neuroscience. 12. 133-139 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H., Kusano K., Suzuki K., Tokoro T. and Eto Y.: "Galactosylceramides and galactosylsphingosine loading studies in cultured skin fibroblasts in human and murine globoid cell leukodystrophy." Biochem. Biophys. Res. Commun.166. 1053-1060 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ida H., Eto Y. and Maekawa K.: "Biochemical pathogenesis of demyelination in globoid cell leukodystrophy (Krabbe's disease) : The effect of psychosine upon oligodendroglial cell culture." Acta Pediater. Jap.32. 20-26 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shimizu H., Eto Y. and Maekawa K.: "Abnormally high urinary polyamine excrations in HHH syndrome. Ida H. and Eto Y. Biochemical and Morphological studies of dorsal root ganglion and its cultured from twitcher mouse (murine globoid cell leukodtstrophy)." Brain and Develop. Brain and Develop.12 12. 533-535 412-416 (1990 1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugama S., Kim S. U., Ida H, and Eto Y.: "Psychosine cytotoxicity in rat neural cell cultures and protection by phorbol ester and olimethyl sulfoxide." Pediatr. Res.28. 473-476 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taka K., Kobayashi T., Goto I., Ohno K., Eto Y., Inui K. and S. Okada: "Lysosulfatide (sulfogalactosylsphingosine) accmulation in tissues from patients with metachromatic leukodystrophy." J. Neurochem.55. 1583-1591 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tahara T. Kraus J. P. and Rosenberg L. E.: "An usual insertion/deletion in the gene encoding the betasubunit of proponyl CoA carboxylase is a frequent mutation in Caucasian propionic academia." Proc. Natl. Acad. Sci. (USA). 87. 1372-1376 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tahara T., Kraus J. P. and Rosengerg L. E.: "Direct DNA sequencing of PCR amplified genomic DNA by the Maxam-Gilbert method." Bio Technique. 8. 366-368 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugama S., Eto Y., Yamamoto H., Kim S. U.: "Psychosine cytotoxicity toward rat C6 glioma cells and the protective effects of phorbol ester and dimethylsulfoxide : Implication for therapy in krabbe disease." Brain and Develop.13. 104-109 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kawame H., Eto Y.: "A New Glucocerebrosidase-Gene Missense Mutation Responsible for Neuronopathic Gaucher Disease in Japanease Patients." Am J. Hum Genet. 49. 1378-1380 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kawame H.,Eto Y.: "A New Glucocerebrosidase-Gene Missense Mutation Responsible for Neuronopathic Gacher Disease in Japanese Datients." Am.J Hum Genet. 49. 1378-1380 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ida H.,Eto Y.,Maekawa K.: "Biochemical pathogensis of demyelination in globoid cell Leukodystvophy(Krabbe's disease)" Acta Pediatr.Jap.32. 20-26 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ida H.,Eto Y.: "Biochemical and Morphological studies of dorsal root ganglion and its cultured from twitcher mouse" Brain and Develop. 12. 412-416 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 衛藤 義勝: "ライソゾ-ム病の骨髄移殖による治療法の最近の進歩" 小児科診療. 43. 645-651 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ida H.,Eto Y.Maekawa K.: "Fetal GM_1-gangliosidosis:Morphological and biochemical studies." Brain and Develop.11. 394-398 (1989)

    • Related Report
      1991 Annual Research Report
  • [Publications] 衛藤 義勝: "遺伝子組み変え技術により作製した天然ヒト成長ホルモン製剤,SJ-0011の下垂体性小人症に対する臨床試験" 薬理と治療. 17. 465-486 (1989)

    • Related Report
      1991 Annual Research Report
  • [Publications] 衛藤 義勝,永津 俊治他編: "脳と遺伝子" 平凡社, 11 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 衛藤 義勝,中村 治雄編: "脂質の科学" 朝倉書店, 18 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Umezawa F・x ETO Y: "αーmannosglated liqosome in cultured cells" Brain Reselarch. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ida H.,Eto Y.Maekawak.: "Fefal GM_1ーガングリオシドシス" Brain x Development. 11. 394-8 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matui K.,Shirasawa N,and Y,Eto: "Cytoplasmic Accumulations in rat Primary Brain cells cultuaed following treatment with Eー64." Developmental Neuros cience.12. 133-139 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ida H.Eto Y.X Maekawa K.: "Biochemical Pathogenesis of demynalination in globoid cells Leukodyrhophy." Acta Pecliat Jap.32. 20-26 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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