Analysis of mechanisms underlying chemotherapy-induced peripheral neuropathy and screening its prophylactic/therapeutic drugs
| Project/Area Number |
17H04008
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
金子 周司 京都大学, 薬学研究科, 教授 (60177516)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
|---|
| Keywords | 薬理学 / 医療薬学 / 抗がん剤誘発末梢神経障害 / シュワン細胞 / 有害事象ビッグデータ / ドラッグリポジショニング / ガレクチン-3 / スクリーニング / 有害事象ビッグデータ解析 / ドラッグ・リポジショニング |
|---|
| Outline of Final Research Achievements |
In this study, we found that taxane-based anti-cancer drugs are involved in the induction of chemotherapy-induced peripheral neuropathy (CIPN) through the dedifferentiation of periaxial Schwann cells and increased release of galectin-3, which induces macrophage infiltration into the peripheral neurons. Thus, we screened drugs that are capable of inducing Schwann cell differentiation from several drug/compound libraries, and successfully obtained several candidates, including PDE inhibitors and other compounds. In addition, we confirmed that these candidate drugs prevent Schwann cell dedifferentiation and mechanical hypersensitivity in a mouse model of taxane-induced CIPN. Furthermore, by using analysis of adverse event big data FAERS, we searched for concomitant drugs that can inhibit CIPN, and selected several candidate drugs. We confirmed that some of them were effective in the CIPN mouse model.
|
| Academic Significance and Societal Importance of the Research Achievements |
CIPNはがん治療中で高率に見られる副作用であり、がん患者のQOLやADLを低下させるだけでなく、重症化によりがん治療継続に深刻な影響を与えることもある。未だCIPNの予防/治療法は確立されておらず、アンメットニーズの高い領域である。高齢化に伴い増加するがん患者あるいはがんサバイバーにとって、CIPN予防/治療薬の開発は有益性が高く、安心してがん治療に望むことが可能となる。本研究は、研究代表者がこれまで得てきた研究基盤をもとに、独自の手法によりその候補薬を得ることに成功したものである、また、その多くが既存薬であることから、今後比較的早期にCIPN予防/治療薬開発に着手できると考えている。
|
Report
(4 results)
Research Products
(46 results)
