Nerve growth factor (NGF) inhibitors are a class of compounds that inhibit the action of the neurotrophin nerve growth factor by targeting NGF molecules or NGF receptors. NGF inhibitors have demonstrated therapeutic potential in treatment of certain chronic pain disorders, including osteoarthritis, and chronic lower back pain.[1] Two NGF inhibitors (tanezumab, and fasinumab) are undergoing clinical trials as potential treatments for pain disorders.[2]
| Nerve growth factor inhibitor | |
|---|---|
| Drug class | |
| Class identifiers | |
| Use | Osteoarthritis |
| Biological target | Neurotrophin pathway |
| Legal status | |
| In Wikidata | |
Medical uses edit
Osteoarthritis edit
In clinical studies, NGF inhibitors have demonstrated efficacy in reducing pain and improving function in persons with knee or hip osteoarthritis.[2] While injectable NGF inhibitors (anti-NGF antibodies) have demonstrated greater efficacy in pain relief compared to NSAID and opioid medications,[3] those receiving the treatment were more likely to experience rapid progression of the disease, necessitating surgical treatment (especially if also taking NSAIDs concurrently).[4]
Mechanism of action edit
NGF is involved in pain signalling.[2] The exact role of NGF signalling in chronic pain is not fully understood, and multiple mechanisms are thought to be involved. NGF is released by immune cells in response to peripheral injury, and is thought to promote neural sensitisation, and neural sprouting. Elevated NGF levels are seen in those with chronic pain conditions (including interstitial cystitis, prostatitis, arthritis, pancreatitis, chronic headaches, cancer pain, and diabetic neuropathy[5]), and injection of NGF causes allodynia and hyperalgesia.[6]
NGF inhibitors may take the form of monoclonal antibodies that bind to NGF, or small molecule inhibitors of NGF receptors.[2] NGF inhibition may be achieved by sequestering free NGF molecules, blocking receptor binding, or inhibiting receptor function. Anti-NGF antibodies have demonstrated the greatest promise as potential medications.[5]
References edit
- ^ Oo, Win Min; Hunter, David J. (2021-11-01). "Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review". BioDrugs. 35 (6): 611–641. doi:10.1007/s40259-021-00504-8. ISSN 1179-190X. PMID 34807432. S2CID 244509341.
- ^ a b c d Wise BL, Seidel MF, Lane NE (January 2021). "The evolution of nerve growth factor inhibition in clinical medicine". Nature Reviews. Rheumatology. 17 (1): 34–46. doi:10.1038/s41584-020-00528-4. PMID 33219344. S2CID 227065883.
- ^ Cao Z, Zhou J, Long Z, Li Y, Sun J, Luo Y, Wang W (December 2020). "Targeting nerve growth factor, a new option for treatment of osteoarthritis: a network meta-analysis of comparative efficacy and safety with traditional drugs". Aging. 13 (1): 1051–1070. doi:10.18632/aging.202232. PMC 7835067. PMID 33293475.
- ^ Katz JN, Arant KR, Loeser RF (February 2021). "Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review". JAMA. 325 (6): 568–578. doi:10.1001/jama.2020.22171. ISSN 0098-7484. PMC 8225295. PMID 33560326.
- ^ a b Chang DS, Hsu E, Hottinger DG, Cohen SP (2016-06-08). "Anti-nerve growth factor in pain management: current evidence". Journal of Pain Research. 9: 373–83. doi:10.2147/JPR.S89061. PMC 4908933. PMID 27354823.
- ^ Schmelz M, Mantyh P, Malfait AM, Farrar J, Yaksh T, Tive L, Viktrup L (October 2019). "Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety". Pain. 160 (10): 2210–2220. doi:10.1097/j.pain.0000000000001625. PMC 6756297. PMID 31145219.