title: Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial.
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 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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. pcampo@jhmi.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Syed Mahmood
authors.initials: SM
authors.lastname: Shah
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.forename: Eric
authors.initials: E
authors.lastname: Holz
authors.forename: Robert N
authors.initials: RN
authors.lastname: Frank
authors.forename: David A
authors.initials: DA
authors.lastname: Saperstein
authors.forename: Anurag
authors.initials: A
authors.lastname: Gupta
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Stout
authors.forename: Jennifer
authors.initials: J
authors.lastname: Macko
authors.forename: Robert
authors.initials: R
authors.lastname: DiBartolomeo
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Wei
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000235:genetics* / Q000494:pharmacology; D005260:Female; D005451:Fluorescein Angiography; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics* / Q000494:pharmacology; D015843:Serpins / Q000235:genetics* / Q000494:pharmacology; D013183:Sputum / Q000821:virology; D016896:Treatment Outcome; D014556:Urine / Q000821:virology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor