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 |
Research Field |
Applied pharmacology
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Research Institution | The University of Tokushima |
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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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
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 / 酵素トラフィキング / iPS細胞 / 糖鎖レセプター / シグナル伝達 / 単球/マクロファージ |
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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Report
(3 results)
Research Products
(72 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 D, T. Hirokawa, K. Itoh, T.Yoshida, H. Chuman
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Journal Title
Chem-Bio Informatics Journal
Volume: 13
Issue: 0
Pages: 30-44
DOI
NAID
ISSN
1347-0442, 1347-6297
Related Report
Peer Reviewed
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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)
Issue: 12
Pages: e83905-e83905
DOI
Related Report
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)
Related Report
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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)
Related Report
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)
Related Report
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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 cells.
Author(s)
Kouji Itou, Daisuke Tsuji, Mariko Ikuo, Keisuke Kitakaze, So-ichirou Nishioka, Izumi Imataki, Saeka Yamaguchi, Yasunori Chiba, Hitoshi Sakuraba, Isao Kobayashi, Hideki Sezutsu and Hiroaki Machii
Organizer
The IUBMB 10th International Symposium on Cell Surface Macromolecules
Place of Presentation
Saha Institute of Nuclear Physics,Kolkata(India)
Related Report
Invited
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[Presentation] Molecular properties of recombinant human lysosomal enzyme produced by transgenic silkworm and therapeutic potential for lysosomal storage disease.
Author(s)
Kouji Itou, Daisuke Tsuji, So-ichirou Nishioka, Syunsuke Ikedo, Tetuya Higashi, I Kobayashi, H Sezutsu, A Ishii, K. Harazono, M. Tada, Nana Kawasaki and Hiroaki Machii
Organizer
Gordon Research Conference 2013 Lysosomal Diseases
Place of Presentation
Renaissance Tuscany Il Ciocco Resort ,Lucca(Italy)
Related Report
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[Presentation] リソソーム病治療薬候補としてのトランスジェニックカイコ絹糸腺由来組換えヒトカテプシンAの機能解析と分子装飾
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第4回グライコバイオロジクス研究会プログラム
Place of Presentation
札幌市民ホール(北海道)
Related Report
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[Presentation] 新規機能性RNA psm-mecはagrA遺伝子の翻訳を抑制してメチシリン耐性黄色ブドウ球菌の病原性を抑制する
Author(s)
幾尾 真理子, 齋藤 裕樹, 大前 陽輔, 毛 瀚, 長野 源太郎, 藤幸 知子, 沼田 俊介, 韓 笑, 小幡 佳津明, 長谷川 節雄, 山口 博樹, 猪口 孝一, 伊藤 輝代, 平松 啓一, 伊藤 孝司, 関水 和久, 垣内 力
Organizer
第86回日本生化学会大会
Place of Presentation
パシフィコ横浜(神奈川県)
Related Report
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[Presentation] ガラクシアリドーシス治療薬候補としてのトランスジェニックカイコ由来ヒトカテプシンAの解析
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第86回日本生化学会大会
Place of Presentation
パシフィコ横浜(神奈川県)
Related Report
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[Presentation] バイオ医薬品の生産基材としてのトランスジェニックカイコとネオグライコバイオロジクス創製への応用
Author(s)
伊藤 孝司, 小林 巧, 西岡 宗一郎, 原園 景, 久保 勇樹, 真板 宣夫, 辻 大輔, Md Motiiur RAHMAN, 池戸 駿介, 石井 明子, 川崎 ナナ, 町井 博明, 瀬筒 秀樹
Organizer
第32回日本糖質学会大会
Place of Presentation
大阪国際交流センター (大阪府)
Related Report
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[Presentation] ガラクシアリドーシス治療薬候補としてのトランスジェニックカイコ由来ヒトカテプシンAの解析
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第54回日本生化学会中国・四国支部例会
Place of Presentation
徳島大学(徳島県)
Related Report
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