Nerve Growth Factor

Summary

Nerve Growth Factor (NGF) is an endogenous neurotrophin critical for the development and maintenance of peripheral sympathetic and sensory neurons. Recombinant human NGF (rhNGF, cenegermin) has been approved for the treatment of neurotrophic keratitis. Anti-NGF antibodies (tanezumab, fasinumab) have been investigated as analgesics. NGF itself is also under investigation for various neurodegenerative and ocular indications.

Mechanism of Action

Binds to TrkA (high-affinity) and p75NTR (low-affinity) receptors, activating downstream signaling cascades (MAPK, PI3K/Akt, PLCγ) that promote neuronal survival, differentiation, axonal growth, and maintenance of sympathetic and sensory neurons; also modulates pain signaling via sensitization of nociceptors.

Routes of Administration

Goals & Uses

• Neuroprotection in Alzheimer's diseaseNeurologyLow
• Dry eye diseaseOphthalmologyModerate
• Wound healing / corneal regenerationOphthalmology / DermatologyModerate
• Peripheral neuropathy treatmentNeurologyLow
• Treatment of neurotrophic keratitisOphthalmologyHigh

Contraindications

• Hypersensitivity to NGF or formulation componentsAllergyHigh
• PregnancyPopulationModeratePotential fetal risk or insufficient safety data
• Active ocular infectionOphthalmologyHigh

Adverse Effects

• Systemic hyperalgesia / myalgiaNeurological / MusculoskeletalCommon
• Ocular hyperemiaOphthalmologicCommon
• Injection site painLocalCommonPain at the injection site
• Corneal deposits (topical)OphthalmologicUncommon
• Eye pain / foreign body sensationOphthalmologicCommon

Drug Interactions

• Anti-NGF antibodies (tanezumab, fasinumab)High
• NSAIDs / AnalgesicsModerate
• Corticosteroids (topical ocular)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Patients with chronic pain conditionsComorbidityRelative
• Immunocompromised patientsImmunologicRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionApprovedApproved: Neurotrophic keratitis (moderate to severe, stages 2 and 3)EMA approval granted in July 2017 under exceptional circumstances; marketed as Oxervate by Dompé.
• United StatesApprovedApproved: Neurotrophic keratitis (stages 2 and 3)Cenegermin (Oxervate) approved by FDA in August 2018; first drug approved for neurotrophic keratitis in the US.
• United KingdomApprovedApproved: Neurotrophic keratitis (stages 2 and 3)Approved post-Brexit via MHRA recognition of EMA approval; available as Oxervate.

Cenegermin (Oxervate), a recombinant form of human NGF, received FDA approval in 2018 and EMA approval in 2017 for neurotrophic keratitis. Systemic NGF therapies remain largely investigational. Anti-NGF antibodies faced FDA holds due to joint safety concerns.

Evidence & Sources

No sources recorded yet.