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用于控制犬猫疼痛的抗神经生长因子单克隆抗体。

Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats.

作者信息

Enomoto Masataka, Mantyh Patrick W, Murrell Joanna, Innes John F, Lascelles B Duncan X

机构信息

Translational Research in Pain, Comparative Pain Research and Education Centre, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

Cancer Center's Cancer Biology Program, Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA.

出版信息

Vet Rec. 2019 Jan 5;184(1):23. doi: 10.1136/vr.104590. Epub 2018 Oct 27.

Abstract

Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.

摘要

神经生长因子(NGF)对于发育过程中感觉神经元和交感神经元的存活至关重要。然而,在成体中,已发现NGF及其与原肌球蛋白受体激酶A受体(TrkA)的相互作用在疼痛状态下的伤害感受和神经系统可塑性中起关键作用。因此,在开发用于慢性疼痛的新药疗法过程中,已对各种靶向该途径的单克隆抗体(mAb)疗法进行了研究。尽管尚无针对NGF的单克隆抗体被批准用于人类,但它们在有效控制疼痛方面看起来非常有前景。最近,已开发出用于治疗犬猫骨关节炎(OA)相关疼痛的物种特异性抗NGF单克隆抗体,并已进行了早期临床试验。抗NGF疗法作为一种针对犬猫慢性疼痛的新型疗法,看起来既非常有效又非常有前景。本综述概述了NGF的作用机制、NGF在骨关节炎中的作用、在啮齿动物OA模型中的研究以及抗NGF单克隆抗体在人类中的开发现状。此外,我们描述并讨论了用于治疗兽医学中OA相关疼痛的物种特异性抗NGF单克隆抗体的最新进展。

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