NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats
文献类型：期刊论文
| 作者 | Liang, Zhi-juan2,3; Tan, Jie1,4; Tang, Lei1; Xie, Zuo-bin1; Chen, Gan-jun1,4; Liu, Guo-jian1; Yuan, Lin1; Wang, Kai-xin1; Ding, Hua-ping1; Qiu, Hong2 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2022-04-25 |
| 页码 | 7 |
| 关键词 | nerve growth factor neuropathic pain chemotherapy monoclonal antibody |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-022-00904-8 |
| 通讯作者 | Wang, Chun-he(wangc@simm.ac.cn) |
| 英文摘要 | Chemotherapy-induced peripheral neuropathy (CIPN) is one of the pervasive side effects of chemotherapy, leading to poor quality of life in cancer patients. Discovery of powerful analgesics for CIPN is an urgent and substantial clinical need. Nerve growth factor (NGF), a classic neurotrophic factor, has been identified as a potential therapeutic target for pain. In this study, we generated a humanized NGF monoclonal antibody (DS002) that most effectively blocked the interaction between NGF and tropomyosin receptor kinase A (TrkA). We showed that DS002 blocked NGF binding to TrkA in a dose-dependent manner with an IC50 value of 6.6 nM; DS002 dose-dependently inhibited the proliferation of TF-1 cells by blocking the TrkA-mediated downstream signaling pathway. Furthermore, DS002 did not display noticeable species differences in its binding and blocking abilities. In three chemotherapy-induced rat models of CIPN, subcutaneous injection of DS002 produced a significant prophylactic effect against paclitaxel-, cisplatin- and vincristine-induced peripheral neuropathy. In conclusion, we demonstrate for the first time that an NGF inhibitor effectively alleviates pain in animal models of CIPN. DS002 has the potential to treat CIPN pain in the clinic. |
| WOS关键词 | NERVE GROWTH-FACTOR ; PAIN ; TANEZUMAB ; OSTEOARTHRITIS ; NEUROTROPHINS ; DULOXETINE ; ANTAGONISM ; ALLODYNIA ; EFFICACY ; RELIEF |
| 资助项目 | China National Major Scientific and Technological Special Project[2019ZX09732002-006] ; National Natural Science Foundation of China[81872785] ; National Natural Science Foundation of China[81673347] ; Shanghai Municipal Commission of Science and Technology of China[17431904400] ; Shanghai Municipal Commission of Science and Technology of China[19YF1457400] ; Shanghai Municipal Commission of Science and Technology of China[21S11904500] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120202007] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120202008] ; Major Scientific and Technological Special Project of Zhongshan City[191022172638719] ; Major Scientific and Technological Special Project of Zhongshan City[210205143867019] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000787125900002 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299499]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Chun-he |
| 作者单位 | 1.Dartsbio Pharmaceut Ltd, Zhongshan 528400, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Shanghai Mabstone Biotechnol Ltd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liang, Zhi-juan,Tan, Jie,Tang, Lei,et al. NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats[J]. ACTA PHARMACOLOGICA SINICA,2022:7. |
| APA | Liang, Zhi-juan.,Tan, Jie.,Tang, Lei.,Xie, Zuo-bin.,Chen, Gan-jun.,...&Wang, Chun-he.(2022).NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats.ACTA PHARMACOLOGICA SINICA,7. |
| MLA | Liang, Zhi-juan,et al."NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats".ACTA PHARMACOLOGICA SINICA (2022):7. |
入库方式： OAI收割
来源：上海药物研究所
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