Investigational Neuroprotective Compounds in Clinical Trials for Retinal Disease.

INTRODUCTION The death of retinal neurons causes permanent and irreversible vision loss, severely impairing quality of life. By targeting toxic conditions which cause neuronal death, such as oxidative stress and ischaemia, neuroprotective agents provide utility in slowing or stopping sight loss resulting from eye disease. While clinical use of neuroprotectants remains limited, there are a few promising compounds presently in early clinical trials (pre-phase III) which may fulfil exciting new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify relevant compounds. AREAS COVERED This review focuses research supporting neuroprotective compounds in eye diseases which range from preclinical stages to phase II, as listed on the clinicaltrials.gov database. The compounds under discussion, namely NGF, Saffron, Ubiquinone, and CNTF, are discussed in terms of potential clinical applications in the near future. EXPERT OPINION Until recently, the major challenge in neuroprotection research has been the successful translation from basic research to the clinic. A number of potential neuroprotective molecules have progressed to ophthalmology clinical trials in the last few years, with defined mechanisms of action - saffron and CoQ10 - targeting the mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and choice of patient cohorts in these chronic diseases using proof-of-concept trials with enriched patient populations and surrogate endpoints should increase drug development speed. A further important consideration is optimising drug delivery approaches with improvements in individualised management and patient compliance. Progress in all these areas means that neuroprotective strategies have a much improved chance nowadays of translational success.