The pathway of a "Nobel" molecule: The Nerve Growth Factor and prospects for treatment of rare eye diseases leading the international round table sponsored by Dompé

A common thread runs through the discovery of the Nerve Growth Factor (NGF) by Rita Levi Montalcini on the prospects for the treatment of rare and orphan eye diseases: research made in Italy.

Indeed, on the basis of the studies conducted by close collaborators of the great scientist, at the Dompé R&D Centre in L'Aquila the first human recombinant variant of NGF for clinical use in ophthalmology was developed. Objective: to identify a possible treatment for curing pathologies such as neurotrophic keratitis, which is a serious disease of the cornea, which affects less than one person in 5,000 in the world. Topics of the international round table "New therapeutic horizons in Ophthalmology: research and innovation in rare diseases of the eye. The rhNGF case”, which has gathered exponents of international relevance in L'Aquila for an assessment of the present, and especially, the future of the ophthalmologic research related to rhNGF.

In the context of the evolution of the molecule, the REPARO Study proposes an assessment of its effectiveness and safety, with the contribution of 39 centres of excellence in 9 European countries.

"I have followed the development of this potential treatment for corneal diseases since 1998, when the first experimental results related to the use of the murine form of NGF appeared, and I used murine NGF for one compassionate case at the end of the nineties - stated Hon. Prof. John Dart, University College London, Consultant Ophthalmologist Moorfields Eye Hospital and Principal Investigator of the study in the United Kingdom. Currently, I have had the opportunity to treat five cases with rhNGF: four have been in the context of the REPARO Study and one case was treated with 20 µg rhNGF which was supplied by Dompé for compassionate use. Our experience has been of rapid healing of the corneal ulcers in three patients in the trial, with a substantial improvement in visual function. The fourth case in the REPARO study has not responded well. In the compassionate use case the patient had  undergone a 4 months of treatment following a corneal transplant for persistent ulceration complicated by infection, had failed all conventional treatments including a repeat transplant, and was at high risk of corneal perforation, a circumstance that would have resulted in blindness. RhNGF treatment resulted in rapid healing and the patient has now been off all treatment for three months with a stable ocular surface, her sight has improved and she has been able to return to a normal life".

The Nerve Growth Factor identified by Rita Levi Montalcini - who was awarded the Nobel Prize in 1986 for this discovery - is a protein that stimulates the growth, maintenance and survival of neurons. A group of the scientist's students, led by Prof. Stefano Bonini, Director of the Department of Ophthalmology of the University of Rome "Campus Bio-Medico" - one of the first researchers in the world to have conducted studies on the use of NGF in the ophthalmic area - realised its possible use in the treatment of corneal diseases, the most innervated organ of the human body, and in particular of neurotrophic keratitis. "Neurotrophic keratitis is a serious degenerative eye disease caused by reduced innervation of the cornea, which can lead to ulceration and perforation of this membrane with consequent loss of sight - said Prof. Bonini. It may result from various clinical conditions, such as diabetes or herpes lesions, and from neurosurgery. We conducted a series of experimental and clinical observations on the use of NGF in neurotrophic keratitis; we treated over 100 patients with the protein of murine origin. The results were encouraging, so much so that Dompé took up the challenge by developing the molecule for clinical use. Today, after years of study, we are satisfied with the concreteness of the intuitions of our research, also confirmed by the promising results of the REPARO study. This result has allowed us to quickly develop a drug for clinical assessment."

The development of the recombinant form of human NGF for ophthalmic use is the outcome of a winning combination of experimental research and industrial innovation of the biotech sector.

"We are very pleased to host this international round table focusing on topics, such as the value of research made in Italy and therapeutic possibilities in ophthalmology, that represent a cornerstone of the mission and strategy of the Group - explains Eugenio Aringhieri, CEO of the Dompé Group. Thanks to the ability of our Centre in L'Aquila to generate innovation, we have developed the only human variant of NGF for clinical use. This encourages us to continue in the identification and development of new therapies for the protection of the needs of patients worldwide. Indeed, we are working to ensure that the first drugs for this therapeutic area can be made available within the next future, also owing to the fundamental contribution of a network of excellence which includes centres leading the way at international level".

RhNGF is also currently being tested in clinical trials for the treatment of Dry Eye (or "dry eye syndrome") and pathologies of the rear part of the eye, such as Retinitis Pigmentosa.