2020 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Aichi Medical University |
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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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| Keywords | 脊髄損傷 / 神経再生 / コンドロイチン硫酸 / 核酸医薬 |
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| 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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| Free Research Field |
神経科学、再生医療、細胞生物学
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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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