April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Safety & Efficacy of Intravitreal Anti-VEGF Gene Delivery in Non-Human Primates for the Treatment of Ocular Neovascularization
Author Affiliations & Notes
  • A. Scaria
    Molecular Biology,
    Genzyme Corporation, Framingham, Massachusetts
  • T. MacLachlan
    Pharmacology/Toxicology, Genzyme, Framingham, Massachusetts
  • M. Lukason
    Molecular Biology,
    Genzyme Corporation, Framingham, Massachusetts
  • P. Pechan
    Molecular Biology,
    Genzyme Corporation, Framingham, Massachusetts
  • E. DuFresne
    Molecular Biology,
    Genzyme Corporation, Framingham, Massachusetts
  • L. Isenberger
    Genzyme Corporation, Framingham, Massachusetts
  • G. Veres
    AGTC, Alachua, Florida
  • I. K. Kim
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • W. Hauswirth
    Ophthalmology, Univ of Florida, Gainesville, Florida
  • S. Wadsworth
    Translational Research,
    Genzyme Corporation, Framingham, Massachusetts
  • Footnotes
    Commercial Relationships  A. Scaria, Genzyme Corporation, E; T. MacLachlan, Genzyme Corporation, E; M. Lukason, Genzyme Corporation, E; P. Pechan, Genzyme Corporation, E; E. DuFresne, Genzyme Corporation, E; L. Isenberger, Genzyme Corporation, E; G. Veres, AGTC Corporation, E; I.K. Kim, None; W. Hauswirth, None; S. Wadsworth, Genzyme Corporation, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4751. doi:
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      A. Scaria, T. MacLachlan, M. Lukason, P. Pechan, E. DuFresne, L. Isenberger, G. Veres, I. K. Kim, W. Hauswirth, S. Wadsworth; Safety & Efficacy of Intravitreal Anti-VEGF Gene Delivery in Non-Human Primates for the Treatment of Ocular Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4751.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To demonstrate safety and efficacy of intravitreal delivery of an adeno associated viral (AAV2) vector expressing an anti-VEGF molecule (sFLT01) in non-human primate models. We have previously shown that AAV2-sFLT01 inhibits neovascularization in the oxygen induced retinopathy model and in the laser-CNV model in mice.

Methods: : A 12 month safety study of AAV2-sFLT01 administered intravitreally in cynomolgus monkeys was performed. Animals were dosed with vehicle, 2E9 or 2E10 vector particles/eye. Assessments included ocular examination, ERGs, FAs and IOP measurements. Efficacy of AAV2-sFLT01 was investigated in the primate model of laser induced-CNV

Results: : Efficacy was demonstrated at 5 months post vector injection in the primate model of laser-CNV. In the eyes of primates, AAV2-sFLT01 gives persistent expression levels for at least one year. Self-limiting mild to moderate vitreal haze and cells were observed only in the high dose group and AAV2 capsid protein has been identified as the source of inflammation. Circulating antibodies to AAV2 were detected in all treated animals and a mild T-cell response against AAV2 capsid peptides was seen only in 3 out of 15 monkeys tested. However no immune responses to sFLT01 were detected. ERG, FA and IOP measurements revealed no test article-related adverse events. Histological evaluation of the eyes in this study found no structural changes in any part of the eye including the retina.

Conclusions: : We have demonstrated long term efficacy with minimal side effects following intravitreal delivery of AAV2-sFLT01 in rodent and primate models. Current treatments of neovascular AMD with VEGF antagonists require monthly injections. Our results suggest an alternate method of long-term treatment for diseases involving ocular neovascularization without the need for repeated injections.

Keywords: age-related macular degeneration • gene transfer/gene therapy • neovascularization 

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