| Project/Area Number |
13557070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pediatrics
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| Research Institution | Tottori University |
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Principal Investigator |
NANBA Eiji Tottori University, Research Center for Bioscience and Technology, Professor, 生命機能研究支援センター, 教授 (40237631)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoshiyuki International University of Health and Welfare, Clinical Research Center, Professor, 臨床医学研究センター, 教授 (90010389)
MAEGAWA Shinji Tottori University, Research Center for Bioscience and Technology, Assistant Professor, 生命機能研究支援センター, 助手 (70314606)
山本 俊至 鳥取大学, 遺伝子実験施設, 助手 (20252851)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | chemical chaperon / treatment / lysosomal storage disease / 低分子物質 / 先天代謝異常 / GM1-ガングリオシドーシス / 中枢神経障害 / 先天代謝異常症 / G_<M1>-ガングリオドシドーシス |
|---|
| Research Abstract |
The chemical chaperon therapy for inherited metabolic diseases including GM1-gangliosidois have been developed in the study. GM1-gangliosidosis which caused by deficiency of β-galactosidase in lysosome, is manifested by central nervous involvement. A new therapeutic method have been developed in the study. Initially more than 27 types of murine model cells containing human β-galactosidase mutation have been created. A galactose derivative, N-octyl-4-epi-β-valienamine (NOEV), which is a potent inhibitor of lysosomal β-galactosidase in vitro, was synthesized. Addition of NOEV in the culture medium restored mutant enzyme activity in murine model cells, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1gangliosidosis resulted in significant enhancement of the enzyme activity in the brain and other tissues. Chemical chaperon therapy may be useful for certain patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
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