2020 Fiscal Year Final Research Report
A novel therapeutic strategy for ALS with induction of differentiation to M2 microglia by targeted gene delivery
| Project/Area Number |
18K07498
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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 52020:Neurology-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 筋萎縮性側索硬化症 / ミクログリア / 標的化輸送 / 核酸医薬 / miRNA / ドラッグデリバリーシステム / Molecular ZIP code |
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| Outline of Final Research Achievements |
There is no established treatment for amyotrophic lateral sclerosis, and the development of its treatment is desired as an urgent issue. Therefore, we tried to establish an inducible method of neuroprotective type microglia from pro-inflammatory type by pinpoint gene delivery using the targeted peptides as a new treatment, because microglia are deeply involved in the progression of the disease. In primary cultured microglia, we succeeded in specific labeling of inflammation-inducing microglia and targeted transport of miRNA by gene transport using targeted MG1, and confirmed the miRNA effect on cell phenotype. In addition, administration of the microglial target peptide + miRNA complex to ALS model animals was shown to suppress the progression of pathological conditions and improve the survival curve.
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| Free Research Field |
遺伝子治療 再生医療 脳神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
筋萎縮性側索硬化症は難治性疾患であり、今回の新規治療法開発は、今後の臨床応用を期待させる大変社会的意義の高い研究成果であると言える。また、標的化ペプチドを用いて核酸を輸送することで、内因性の炎症惹起型のミクログリア細胞を神経保護型に誘導する戦略は、外部からの移植を用いる細胞治療やウイルスベクターを用いた遺伝子治療に比べ、免疫反応を最小限に抑えることができ、安全性が高く、他のミクログリア細胞が関与する神経疾患に対する治療への汎用性もあることから、多くの疾患治療研究の礎となる可能性もあり、学術的意義も非常に高いと考える。
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