| Project/Area Number |
18K06593
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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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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
Shimizu Kosuke 浜松医科大学, 光尖端医学教育研究センター, 准教授 (30423841)
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| Co-Investigator(Kenkyū-buntansha) |
浅井 知浩 静岡県立大学, 薬学部, 教授 (00381731)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 自己免疫疾患治療 / ドラッグデリバリーシステム / 自己抗原修飾リポソーム / 多発性硬化症 / 実験的自己免疫性脳脊髄炎 / 脾臓 / 抗原特異的T細胞 / 標的化DDS / 自己免疫疾患 / T細胞 / 再発寛解型 / フィンゴリモド / 神経免疫疾患 / リポソーム / 逆標的化 |
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| Outline of Final Research Achievements |
The aim of this research is to develop an autoreactive immune cell-targetable approach using autoantigen-modified liposomes for the treatment of multiple sclerosis (MS).
In the experiments, experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic myelin oligodendrocyte glycoprotein peptide (MOG35-55) was used as a model of MS and DOX-encapsulated liposome that has been surficially modified with MOG35-55 (MOG-LipDOX) was used as a therapeutic drug. FACS analysis revealed that the number of MOG-recognizable CD4+ T cells in the spleen was obviously decreased and histological one showed that immune cell invasion into the spinal cord was strongly suppressed after the treatment of EAE with MOG-LipDOX. Therapeutic experiments demonstrated that the progression of encephalomyelitis symptoms of EAE mice was significantly suppressed by MOG-LipDOX. These findings suggest that the use of autoantigen-modified liposome promises to be a suitable therapeutic approach for the cure of MS.
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| Academic Significance and Societal Importance of the Research Achievements |
多発性硬化症（MS）の現行の治療は、ステロイドや免疫抑制剤の投薬により症状を緩和させることで進行や再発を予防できるが根治はできず、また全身的な免疫抑制から生じる感染症発症などの重大な副作用が生じることもあるため問題となっている。本研究成果で確立した自己抗原認識免疫細胞を標的化するDDS戦略により、自己抗原認識T細胞を内封する薬物で直接障害することで自己抗原特異的な免疫反応を抑制し、臨床症状を強く抑えることができるこれまでの治療法とは一線を画す安全かつ有効な治療法を開発できたため、自己免疫疾患治療における新たな標的化DDS戦略の学術的意義、さらには新規MS治療法としての社会的意義は大きい。
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