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

Hum Gene Ther. 2006 Feb;17(2):167-76. doi: 10.1089/hum.2006.17.167.


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 10(6) to 10(9.5) 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 10(6)-10(7.5) PU and 94 and 71% of patients treated with 10(8)-10(9.5) 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 10(8) 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adenoviridae / genetics
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Eye Proteins / genetics*
  • Eye Proteins / pharmacology
  • Female
  • Fluorescein Angiography
  • Genetic Therapy / methods*
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use*
  • Humans
  • Macular Degeneration / diagnosis
  • Macular Degeneration / pathology
  • Macular Degeneration / therapy*
  • Male
  • Middle Aged
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / pharmacology
  • Serpins / genetics*
  • Serpins / pharmacology
  • Sputum / virology
  • Treatment Outcome
  • Urine / virology


  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor