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

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.

Mechanisms that drive bone pain across the lifespan

“…In contrast, localized skin damage produces an acute burst of pain that gradually dies down over minutes but is associated with a spatially restricted response of flair, wheal and surrounding tenderness” . Just why injury to the skeleton is so effective at producing central sensitization remains unclear although the skeleton is innervated by a very distinct population of primary afferent neurons that may be uniquely effective at inducing central sensitization in the spinal cord and higher centres of the brain.…”

Schwann cells and trigeminal neuralgia

“…Theoretically, blocking the interaction between NGF and the trkA receptor could be beneficial for neuropathic pain. In fact, monoclonal antibodies against NGF have been reported to improve chronic neuropathic pain 64,86,87 . NGF-induced trkA receptor activation increases CGRP expression.…”

“…In fact, monoclonal antibodies against NGF have been reported to improve chronic neuropathic pain. 64 , 86 , 87 NGF-induced trkA receptor activation increases CGRP expression. CGRP is an important pain-causing substance and has been targeted in the clinical treatment of TN.…”

Selected Biological Medicinal Products and Their Veterinary Use

“…Two monoclonal antibodies inhibiting the nerve growth factor (NGF) are undergoing clinical trials. These include ranevetmab (NV-01) for dogs and frunevetmab (NV-02) for cats, which are intended for the treatment of chronic pain and degenerative joint disease in cats and dogs [ 81 ].…”