2013 Fiscal Year Final Research Report
Discovery of novel compounds regulating traffic to lysosomes and application for development of therapeutics
| Project/Area Number |
24659262
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied pharmacology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ITOH Kohji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (00184656)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | リソソーム病 / in vivoイメージング / 酵素トラフィッキング / 疾患特異的iPS細胞 / 酵素補充療法 / GM2ガングリオシドーシス / ドラッグデリバリー / 酸性pH活性化蛍光プローブ |
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| Research Abstract |
We studied on intracellular traffic abnormality in lysosomal beta-hexosaminidase (Hex) deficiencies including Tay-Sachs disease (TSD) and Sandhoff diseases (SD) to develop novel enzyme replacement therapy based on techniques to promote delivery of recombinant Hex to lysosomes when extracellularly administrated. We developed modified Hex with high content of mannose 6-phospahte (M6P) residues, which were efficiently incorporated by disease-model cultured cells via cell surface M6P receptors. In addition, we established an iPS cell line derived from a TSD patient, and examined conditions under which neural cells including neural stem cells (NSC) and neural progenitor cells (NPC) could be induced from the TSD iPS cells. Furthermore, we developed novel fluorescent probes including Rhodol beta-GlcNAc as an artificial substrate for intracellular Hex activity and acidic pH-activatable fluorescent Rh-PM for in vivo imaging to detect lysosomal distribution of recombinant Hex.
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Research Products
(13 results)
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[Journal Article] Modeling of Human Neuraminidase-1 and Its Validation by LERE-Correlation Analysis2013
Author(s)
S. Hitaoka, Y. Shibata, H. Matoba, A. Kawano, M. Harada, M.M. Rahman, D. Tsuji, T. Hirokawa, K. Itoh, T. Yoshida, H. Chuman.
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Journal Title
Chem-Bio Informatics Journal
Volume: 13
Pages: 30-44
DOI
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[Journal Article] Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors2013
Author(s)
T. Harada, S. Ozaki, A. Oda, D. Tsuji, A. Ikegame, M. Iwasa, K. Udaka, S. Fujii, S. Nakamura, H. Miki, K. Kagawa, Y. Kuroda, S. Kawai, K. Itoh, H. Yamada-Okabe, T. Matsumoto, M. Abe
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Journal Title
PLoS One
Volume: vol.26:8(12)
Pages: e83905
DOI
Peer Reviewed
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[Presentation] Molecular therapy and evaluation for neurodegenerative GM2 gangliosidoses2014
Author(s)
K. Itoh, D. Tsuji, M. Ikuo, K. Kitakaze, D. Asanuma, M. Kamiya, Y. Urano, E. Sugiyama, M. Setou, M. Yuzaki, H. Sakuraba
Organizer
International symposium "New Frontier of Molecular Neuropathology 2014"
Place of Presentation
Tokyo Medical and Dental University, Tokyo(Japan) (国際・ポスター)
Year and Date
20140316-17
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[Presentation] Establishment of patient-derived iPS cells with neurodegenerative lysosomal storage diseases and application for evaluating lysosomal enzyme replacement effects on differentiated neural cells2014
Author(s)
K. Itoh, D. Tsuji, M. Ikuo, K. Kitakaze, S. Nishioka, I. Imataki, S. Yamaguchi, Y. Chiba, H. Sakuraba, I. Kobayashi, H. Sezutsu, H. Machii
Organizer
The IUBMB 10th International Symposium on Cell Surface Macromolecules, Saha ainstitute of Nuclear
Place of Presentation
Kolkata( India)(国際・招待講演)
Year and Date
20140120-24
Invited
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[Presentation] Imaging of lysosomal enzyme replacement effects with a novel fluorescent probe and imaging mass spectrometry2014
Author(s)
K. Kitakaze, M. Ikuo, E. Sugiyama, D. Asanuma, M. Kamiya, M. Setou, Y. Urano, H. Sakuraba, K. Itoh
Organizer
International Symposium on Glyco-Neuroscience
Place of Presentation
Awazi-yumebutai, Awaji-shima, Hyougo(Japan)(国際・ポスター)
Year and Date
20140109-11
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