NGF

Where it comes from

Made in

The tissues sympathetic and sensory nerves grow into; cortex and hippocampus; mast cells, keratinocytes and the cornea

Sent out by

Inflammation and injury raise it greatly; in the brain, by activity

Acts on

• Sympathetic neurons (survival)
• Pain-sensing neurons (sensitisation)
• Cholinergic neurons of the basal forebrain
• Corneal nerves and epithelium

What it does

• Keeps sympathetic and sensory neurons alive during development; without it they die
• Sensitises pain nerves and is a major driver of inflammatory pain
• Supports the cholinergic neurons that fail in Alzheimer’s disease

In medicine

• Cenegermin, recombinant NGF eye drops, has treated neurotrophic keratitis since 2017 in Europe and 2018 in the US: the first approved neurotrophin ⁴
• Tanezumab and other anti-NGF antibodies relieved osteoarthritis and back pain in trials but caused rapidly worsening joints in some patients, and were turned down in 2021 ²
• Mutations of NGF or TrkA cause congenital insensitivity to pain

Beyond the body’s own use

• The approval rests on randomised evidence: in 156 patients with moderate or severe neurotrophic keratitis, 74 per cent of corneas healed by eight weeks on NGF drops against 43 per cent on vehicle ¹
• Blocking NGF cuts osteoarthritis pain only modestly. In 698 patients the gain over placebo on the pain and function scores was small, rapidly progressive osteoarthritis occurred only in treated patients, and joint replacements were commoner among them ²
• NGF gene therapy into the basal forebrain did not slow Alzheimer’s disease in a randomised trial of 49 people, and whether the vector reached the intended neurons was never confirmed ³
• NGF has no use outside the licensed eye drops, and no anti-NGF antibody is approved anywhere ⁴