Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: Results of a phase I clinical trial

Peter A. Campochiaro, Quan Dong Nguyen, Syed Mahmood Shah, Michael L. Klein, Eric Holz, Robert N. Frank, David A. Saperstein, Anurag Gupta, J. Timothy Stout, Jennifer Macko, Robert DiBartolomeo, Lisa L. Wei

Research output: Contribution to journalArticle

284 Scopus citations

Abstract

Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment epithelium-derived factor (AdPEDF.11). Doses ranging from 106 to 109.5 particle units (PU) were investigated. There were no serious adverse events related to AdPEDF.11 and no dose-limiting toxicities. Signs of mild, transient intraocular inflammation occurred in 25% of patients, but there was no severe inflammation. Six patients experienced increased intraocular pressure that was easily controlled by topical medication. All adenoviral cultures were negative. At 3 and 6 months after injection, 55 and 50%, respectively, of patients treated with 106-107.5 PU and 94 and 71% of patients treated with 108-109.5 PU had no change or improvement in lesion size from baseline. The median increase in lesion size at 6 and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0 and 0 disk areas in the high-dose group. These data suggest the possibility of antiangiogenic activity that may last for several months after a single intravitreous injection of doses greater than 108 PU of AdPEDF.11. This study provides evidence that adenoviral vector-mediated ocular gene transfer is a viable approach for the treatment of ocular disorders and that further studies investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should be performed.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalHuman gene therapy
Volume17
Issue number2
DOIs
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Campochiaro, P. A., Nguyen, Q. D., Shah, S. M., Klein, M. L., Holz, E., Frank, R. N., Saperstein, D. A., Gupta, A., Stout, J. T., Macko, J., DiBartolomeo, R., & Wei, L. L. (2006). Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: Results of a phase I clinical trial. Human gene therapy, 17(2), 167-176. https://doi.org/10.1089/hum.2006.17.167