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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1396790
This article is part of the Research Topic 'Pain and pain-related neuropsychiatric disorders: from mechanistic insights to innovative therapeutic strategies.' View all 4 articles
Effect of the novel anti-NGF monoclonal antibody DS002 on the metabolomics of pain mediators, cartilage and bone
Provisionally accepted
Dandan Jin
1
Haoyi Yang
1
Zhiyou Chen
2*
Yuxin Hong
2
Yuwen Zhang
3*
Hehua Ma
2,4*
Zhenzhen Xu
2,4*
Bei Cao
2,5
Fei Fei
2,5
Weitao Wu
6
Lei Tang
6*
Runbin Sun
7*
Chunhe Wang
6*
Juan Li
2*- 1 Department of Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
- 2 Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
- 3 China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, China
- 4 Nanjing Drum Tower Hospital, Nanjing, China
- 5 Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China
- 6 Dartsbio Pharmaceuticals, Ltd., Zhongshan, China
- 7 Phase I Clinical Trial Research Center, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
The anti-nerve growth factor antibody class of drugs interrupts signaling by blocking NGF binding to TrkA receptors for the treatment of pain; however, this target class of drugs has been associated with serious adverse effects in the joints during clinical trials. DS002 is a novel anti-nerve growth factor antibody drug independently developed by Guangdong Dashi Pharmaceuticals. The main purpose of this study is to explore the correlation between DS002 and pain as well as cartilage and bone metabolism with the help of metabolomics technology and the principle of enzyme-linked reaction, and to examine whether DS002 will produce serious adverse effects in joints caused by its same target class of drugs, in order to provide more scientific basis for the safety and efficacy of DS002. Our results showed that DS002 mainly affected the metabolism of aromatic amino acids and other metabolites, of which six metabolites, l -phenylalanine, 5-hydroxytryptophan, 5-hydroxytryptophan, 3-indolepropionic acid, kynurenine, and kynurenine, were significantly altered, which may be related to the effectiveness of DS002 in treating pain. In addition, there were no significant changes in biological indicators related to cartilage and bone metabolism in vivo, suggesting that DS002 would not have a significant effect on cartilage and bone metabolism, so we hypothesize that DS002 may not produce the serious adverse effects in joints caused by its fellow target analogs. Therefore, the Anti-NGF analgesic drug DS002 has the potential to become a promising drug in the field of analgesia, providing pain patients with an efficient treatment option without adverse effects..
Keywords: Metabolomics, Pain, aromatic amino acids, biomarkers, Anti-NGF drugs
Received: 06 Mar 2024; Accepted: 29 Jul 2024.
Copyright: © 2024 Jin, Yang, Chen, Hong, Zhang, Ma, Xu, Cao, Fei, Wu, Tang, Sun, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhiyou Chen, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
Yuwen Zhang, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, China
Hehua Ma, Nanjing Drum Tower Hospital, Nanjing, China
Zhenzhen Xu, Nanjing Drum Tower Hospital, Nanjing, China
Lei Tang, Dartsbio Pharmaceuticals, Ltd., Zhongshan, China
Runbin Sun, Phase I Clinical Trial Research Center, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
Chunhe Wang, Dartsbio Pharmaceuticals, Ltd., Zhongshan, China
Juan Li, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
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