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Elena Bastia, Francesco Impagnatiello, Nicoletta Almirante, Cecilia Lanzi, Emanuela Masini, Carol B Toris, Ennio Ongini; NCX 667, a novel nitric oxide (NO) donor lowers intraocular pressure (IOP) in ocular normotensive and hypertensive eyes of rabbits and non-human primates. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1999.
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© ARVO (1962-2015); The Authors (2016-present)
The wealth of experimental data from a variety of models coupled with recent clinical studies strongly supports an important role of nitric oxide (NO) in lowering intraocular pressure (IOP) by enhancing aqueous humor drainage via conventional outflow. NCX 667 is a novel NO-donor recently characterized for efficacy and safety in New Zealand white (NZW) rabbits and cynomolgus monkeys with glaucoma.
In an ocular hypertensive model, male NZW rabbits were injected with 0.1 ml of hypertonic saline solution (5%) into the vitreous humor of both eyes. Vehicle (phosphate buffer pH 6.0+cremophor EL 5%+ DMSO 0.3%+BAC 0.2mg/ml) or NCX 667 at different doses was instilled immediately after saline injection. IOP was determined prior to (baseline) hypertonic saline and during the following 5 hours post dosing. Similar dosing regimen and IOP recording were used in ocular normotensive male NZW rabbits. Female cynomolgus monkeys with unilateral laser-induced elevated IOP were used. The contralateral eye was evaluated for IOP changes in normotensive conditions. Baseline IOP was measured the day before dosing while drug-mediated IOP changes were determined by comparing vehicle and treatment groups before dosing and during the following 5 hours.
In ocular normotensive rabbits, NCX 667 topical dosing resulted in IOP decrease of up to -5.3 ± 0.8 mmHg vs. vehicle at 1%. Likewise, instillation of NCX 667 significantly lowered the IOP in ocular hypertensive rabbits with a maximal reduction of -11.8 ± 0.6 mmHg vs. vehicle at 1%. The effects were dose-dependent from 0.1 to 1%. In addition, topical application of NCX 667 1% was effective (-7.3 ± 2.3 mmHg vs. vehicle) in the ocular hypertensive eyes of non-human primates but was only marginally active in the contralateral normotensive eyes. NCX 667 was well tolerated following single topical dosing in rabbits and non-human primates.
NO-donation from NCX 667 leads to IOP lowering in different animal models. Additionally, the initial safety profile is encouraging. Overall, NO-donation from NCX 667 might represent a valid alternative to current IOP-lowering treatments.
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