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Christian Clement, Hilary W. Thompson, Partha S. Bhattacharjee, Harris E. McFerrin, Jr., Walter J. Lukiw, Kara Corbin-Lickfett, Cyril J. Empig, Kyle Schlunegger, James M. Hill; Efficacious Clinical Outcome of an Ophthalmic Formulation of Phosphatidylserine- binding Monoclonal Antibody in a Rabbit Model of Acute HSV-1 Keratitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6155.
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Phosphatidylserine (PS) is a phospholipid found on the internal leaflet of the plasma membrane of normal cells which becomes exposed externally following infection with enveloped viruses. Monoclonal antibodies (mAbs) that recognize PS have the potential to bind infected cells, target them for clearance, and stop infection. The efficacy of the PS-targeting mAb PGN632 given topically was assessed in a rabbit model of HSV-1 keratitis.
Corneas were inoculated bilaterally with 2x106 PFU of HSV-1 strain McKrae following corneal scarification and placed in balanced groups based on slit-lamp examination (SLE) scores (5 rabbits per group). Treatment groups were (1) PGN632, (2) Zirgan® (0.15% ganciclovir), (3) combination of PGN632+Zirgan® (ophthalmic solution followed by ointment), and (4) vehicle. Treatments were given 4 times daily starting 3 days post infection (PI) and continued for 4 consecutive days. SLE was done daily in a masked fashion and eyes were clinically scored daily for epithelial keratitis, stromal damage, scleral inflammation, ocular neovascularization, eyelid inflammation, friability of vasculature, inflammatory discharge, and excessive tearing. Scoring was done each day prior to treatment. SLE and clinical symptomatic scoring were continued on PI days 8, 9, and 10, after drug treatment stopped.
PGN632, Zirgan®, and combination PGN632+Zirgan® treatments resulted in significant reduction of corneal SLE scores (P < 0.05; p values from generalized linear model analysis of scores) and significantly lower clinical scores (P < 0.05) compared with the vehicle. No ocular toxicity was observed in any drug treatment group.
Our data show that the PS-targeting mAb PGN632 is at least equally efficacious compared with Zirgan® in reducing corneal SLE scores and minimizing the ocular clinical symptoms. By providing symptomatic relief in addition to reducing corneal SLE scores, PGN632 could become a drug of choice for treatment of ocular herpes.
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