| Project/Area Number |
17K19722
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
IMAI Satoshi
OGIHARA Takashi
KOYANAGI Madoka
NAKAZATO Yui
MATSUMOTO Mayuna
Iwamitsu Yuki
HAYASHI Maho
NAKAGAWA Shunsaku
Omura Tomohiro
YONEZAWA Atsushi
MATSUBARA Kazuo
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 末梢神経障害 / シュワン細胞 / 抗がん剤 / ドラッグリポジショニング / 痛み / しびれ / トランスレーショナルリサーチ / 再髄鞘化 / ドラッグ・リポジショニング / 糖尿病 / スクリーニング / ガレクチン3 |
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| Outline of Final Research Achievements |
We previously demonstrated that chemotherapy-induced peripheral neuropathy (CIPN) is induced by dedifferentiation of Schwann cells, which form a thin myelin sheet. In this study, we found that treatment of primary cultured rat Schwann cells with taxanes lead to galectin-3 up-regulation and release from dedifferentiated Schwann cells, which can induce infiltration of macrophages into the sciatic nerves and contribute to the induction of CIPN in mice. Furthermore, to develop prophylactic and/or therapeutic drug for CIPN, we found some candidate medicines that can induce differentiation of Schwann cells. Among them, phosphodiesterase inhibitors, such as cilostazol and tadalafil, induced differentiation of cultured Schwann cells and inhibited mechanical hypersensitivity and other symptoms in CIPN mouse model. In addition, we screened and found some candidate compounds that can potentially induce differentiation of Schwann cell from the chemical library of existing medicine.
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| Academic Significance and Societal Importance of the Research Achievements |
CIPNはタキサン系、白金系抗がん剤などのがん治療中に頻繁に見られる副作用の１つで、重症化すればがん治療の継続や治療成績にも深刻な影響を与える。本研究では研究代表者自身が見出した仮説のもと、強力なシュワン細胞誘導能を示す医薬品を同定し、その有効性をCIPN動物モデルで検証した。本研究成果から、CIPNに対する有効な予防/治療薬を開発できるのではないかと期待している。
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