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Recent clinical trials of topically administrated nerve growth factor (NGF) demonstrate that the ocular surface healing and immune-modulating actions of NGF could have widespread therapeutic applications in a wide range of ocular diseases, according to Paolo Rama MD.

“Exogenous NGF is very effective in promoting healing and regeneration and specifically in treating neurotrophic corneal ulcers. In ocular surface diseases, topical NGF may play a role in restoring corneal innervation, improving the tear film and modulating inflammation. It may also be useful for several other ocular disorders such as herpetic keratitis, autoimmune ulcers, glaucoma, various neuropathies, diabetic retinopathy and age-related macular degeneration,” he told delegates attending the 5th EuCornea Congress in London.

Dr Rama explained that NGF was first discovered in the early 1950s by Nobel Prize winner Prof Rita Levi Montalcini and serves as an endogenous human protein that stimulates the growth, maintenance and survival of neurons in the central nervous system.

Surveying the clinical evidence to date, Dr Rama said that NGF was shown to be both safe and effective in the treatment of neurotrophic keratitis in over 100 patients in an open-label study published in 2000. All patients in that trial demonstrated complete healing with only mild transient side effects.

In January 2011, the Italian company Dompé acquired the worldwide rights for the development and commercialisation of NGF and succeeded in producing an enhanced recombinant human (rhNGF) form of the compound.

Dr Rama noted that preliminary data from the phase 1-2 REPARO study, the first international clinical trial evaluating rhNGF eye drops in neurotrophic keratitis, shows corneal healing in more than 70 per cent of masked subjects at eight weeks, with observed reductions in lesion size and symptom improvements.

This efficacy is even more impressive, said Dr Rama, when one considers that the randomisation schedule for phase 2 was 7:2 (rhNGF versus placebo control).

“Four patients that were unmasked for aggravation of their lesions were all under placebo and they all healed when they switched to rhNGF. The key point is that NGF induced not just healing of the corneal lesion but also promoted the restoration of corneal sensitivity,” he said. Dr Rama said that the manufacturers hope to commence a similar study with 48 patients enrolled in 11 centres in the United States in the coming months.

Other potential ocular applications for NGF include dry eye, with an open label cohort study in 20 patients currently ongoing in Austria.

The posterior segment also holds rich potential, said Dr Rama, with the LUMOS phase 1-2 multicentre study in five Italian centres now under way to study rhNGF drops in retinitis pigmentosa, and another one scheduled to commence shortly in Milan.

Plans are also at an advanced stage to assess rhNGF in glaucoma in a phase 1b trial involving 20 patients at two centres in the United States. As well as these trials, other possible targets for NGF treatment in the future include ocular inflammation, herpetic disease, immune stromal keratitis, neuropathies and keratoconus, said Dr Rama.

Paolo Rama:

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