Possibility of treatments for amelioration of spinal cord injury -Regulation of extracellular environments and inflammation control
Project/Area Number |
17K10949
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Aichi Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
玉田 靖 信州大学, 学術研究院繊維学系, 教授 (70370666)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 脊髄損傷 / 神経再生 / コンドロイチン硫酸 / 核酸医薬 / 再生医療 / 細胞外マトリックス / 再生環境制御 / バイオマテリアル / プロテオグリカン / DDS / 再生医学 / 神経科学 / 生体材料 / 移植・再生医療 / 細胞・組織 |
Outline of Final Research Achievements |
Injured adult neurons in the mammalian central nervous system rarely regenerate because some of the intracellular and cell-surface environmental factors inhibit axon regrowth. Chondroitin sulfate (CS) is the most abundant and potent exogenous inhibitor of axonal regeneration. We have showed already that KO mice against CS biosynthesis recovered much faster and more completely than do wild-type mice. We try to establish the accurate inhibition systems of CS-expressions in vivo from the drug screening system, to regulate CS-expressions and modifications in the injury area. We selected the drugs (Antisense oligonucleotide: ASOs) to down-regulate the CS-expressions. The recovery of these mice which treated with drug delivery systems reached the levels of satisfactory amelioration comparable to those of KO mice. Taken together, our results indicated that our screened ASOs delivery system is a promising therapeutic target for treatment of the spinal cord injury and brain infarction.
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Academic Significance and Societal Importance of the Research Achievements |
脊髄損傷の治療において、再生阻害因子除去および糖鎖発現制御による再生環境整備という観点は新しいものである。とくに研究期間中に発現抑制が可能な核酸医薬を選択し、その機能を検討できたことは治療応用につながるものである(現に、企業主導でのヒト応用を目指した創薬導出に繋がっている)。当初計画していた薬剤デリバリーの機材検討は無くとも効果を発揮すること、炎症における核酸医薬デリバリーの新しい機序を見出した。さらに糖鎖を中心とした解析から、脊髄損傷に対しての全く新しい概念シナプスコネクターの可能性を見出し、これら再生環境整備とシナプス結合を統合した全く新しい展望など当初想定外の発見と結果を示すことが出来た
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Report
(5 results)
Research Products
(35 results)
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[Journal Article] Growth cone phosphoproteomics reveals that GAP-43 phosphorylated by JNK is a marker of axon growth and regeneration.2018
Author(s)
Okada M*, Kawasaki A*, Tamada A*, Okuda S, Nozumi M, Ito Y, Kobayashi D, Yamasaki T, Yokoyama R, Shibata T, Nishina H, Yoshida Y, Fujii Y, Takeuchi K, Igarashi M(*These three authorscontributed equally.).
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Journal Title
ISCIENCE
Volume: 4
Pages: 190-203
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex2017
Author(s)
Hou X, Yoshioka N, Tsukano H, Sakai A, Miyata S, Watanabe Y, Yanagawa Y, Sakimura K, Takeuchi K, Kitagawa H, Hensch TK, Shibuki K, Igarashi M, Sugiyama S
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 12646-12646
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Patent(Industrial Property Rights)] 特願2020-0028792020
Inventor(s)
柚崎通介、鈴木邦道、Radu Aricesu,武内恒成
Industrial Property Rights Holder
柚崎通介、鈴木邦道、Radu Aricesu,武内恒成
Industrial Property Rights Type
特許
Industrial Property Number
2020-002879
Filing Date
2020
Acquisition Date
2020
Related Report
Overseas
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