A closer look at nerve growth factor: from biology to clinical trials in ophthalmology

Abstract

Introduction: Nerve growth factor (NGF) is a pleiotropic neurotrophin that extends its biological activity from the CNS and peripheral nervous system to the immune, endocrine and visual systems. A recombinant human NGF (rhNGF) was developed for systemic administration in diabetic and HIV-related neuropathy but it did not reach the market due to the failure of a Phase III study. More recently, experimental and clinical data showed that NGF eye drop treatment may be effective in several ophthalmic diseases, and clinical trials with a new rhNGF eye drops are currently ongoing.

Areas covered: rhNGF produced in Escherichia coli was approved in Europe and in the United States for use in clinical trials in ophthalmic diseases. A Phase I study showed that rhNGF eye drops are safe and well tolerated. rhNGF has recently obtained Orphan Drug Designation for retinitis pigmentosa (RP) and neurotrophic keratopathy and Phase II clinical trials on these conditions are currently ongoing. The authors examine preclinical, pharmacokinetic, safety and efficacy data from the studies using topical ocular NGF.

Expert opinion: Results from preclinical, clinical and safety studies have indicated that rhNGF eye drops represent a promising treatment for ophthalmic diseases currently lacking an effective therapy such as neurotrophic keratitis, RP, dry eye and glaucoma.

Keywords:

• drug development
• nerve growth factor
• neurotrophic keratitis
• neurotrophin
• retinitis pigmentosa

Declaration of interest

F Mantelli, A Lambiase and M Sacchetti are all consultants for Dompé S.p.A. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.