Hamden, CT — March 21, 2011 — RxGen, a specialty preclinical contract research organization, announced today that Experimental Eye Research has published results of efforts to optimize the laser-induced choroidal neovascularization (CNV) model in nonhuman primates, which is routinely employed to evaluate candidate compounds or drug delivery devices designed to treat wet-AMD.
Despite widespread use of the approach, detailed assessments of experimental parameters and their influence on pathopsychological endpoints critical for disease modeling have been extremely limited and largely based on anecdotal observations. RxGen’s efforts focused on the evaluation of laser power parameters and endpoint measures to optimize methods for CNV formation and quantification. The collective methods, data, and conclusions are outlined below and in the publication, which can be found on RxGen’s website.
“Laser parameters and time points for therapeutic dosing and angiography endpoints are critical factors to the laser-induced CNV model and must be validated for robust assessment of efficacy”, comments Matthew Lawrence, RxGen’s Chief Scientific Officer. “We are confident that the newly optimized CNV model in the African green monkey will lend itself to improved decision making as relates to both preclinical and clinical activities for organizations pursuing indications that would benefit from better characterization of choroidal neovascularization. We currently have additional efforts underway to better characterize the CNV complex formation using quantitative optical coherence tomography (OCT), which will also be published in the coming months.”
ABSTRACT SUMMARY
RATIONALE: We developed and validated a new nonhuman primate model of laser-induced CNV that addresses study design limitations prevalent in laser-induced CNV-based efficacy studies. We evaluated laser power parameters and endpoint measures to optimize methods for CNV formation and quantification to facilitate drug efficacy screening in African green monkeys.
METHODS: Six laser spots of 350, 550, 750, 950 or 1500 mW laser power were positioned bilaterally 1.5 disc diameters from the fovea, within the macula. Fluorescein angiograms were collected 3-5 weeks later and scored by trained masked investigators using graded (IeIV) and densitometric methods. Histopathology assessments were also performed, including determination of CNV area. Test system sensitivity to angiogenesis inhibition was subsequently assessed by evaluating the effect of intravitreal bevacizumab (Avastin) pretreatment (one day prior to laser photocoagulation) on incidence of CNV. Grade III and grade IV lesions were considered clinically relevant, demonstrating early hyperfluorescence and late leakage within or beyond the lesion borders.
RESULTS: By 4 weeks post-laser all treatment groups demonstrated evidence of grade III lesions with greatest incidence observed in lesions induced by 750 and 950mW laser power (72.9% and 69.4% respectively). Grade IV lesions were confined to eyes receiving 550 mW laser power or higher, with highest incidence of grade IV lesions observed in eyes receiving 950 (19.4%) and 1500 mW (31%) laser spots, incidence peaking 4 weeks post-laser photocoagulation. Densitometric analyses of angiograms corroborated visual scoring. Bevacizumab completely abolished grade IV lesion development and significantly lowered lesion fluorescein signal intensity (P < 0.0001) and CNV area (P ¼ 0.038) compared to vehicle-treated controls.
CONCLUSIONS: Our studies demonstrate optimal laser power parameters and time point for analysis of CNV induction following laser photocoagulation. Bevacizumab significantly attenuated CNV development, as determined by fluorescein angiography and histopathology assessments in this model, supporting the application of African green monkeys in preclinical modeling of CNV. The newly optimized nonhuman primate model described will facilitate preclinical efficacy assessments of novel therapeutics for CNV.
About RxGen
RxGen, Inc. is a specialty preclinical contract research organization providing innovative in vivo disease modeling and related preclinical research and development services to meet translational research needs in the fields of ophthalmology, central nervous system, and metabolic related disease and disorders. RxGen’s research facilities are AAALAC accredited and GLP compliant, providing a wide range of preclinical research services, from preclinical strategy to in vivo disease modeling and IND-enabling studies.
For more information about RxGen, please visit www.rx-gen.com, or contact:
Christopher Stanley
Chief Business Officer
Direct: (203) 498-9706
E-mail: cstanley@rx-gen.com
