Adenoviral Vector-Delivered Pigment Epithelium-Derived Factor for Neovascular Age-Related Macular Degeneration: Results of a Phase I Clinical Trial

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

doi:10.1089/hum.2005.17.ft-167

Cited by 49 publications

(64 citation statements)

References 8 publications

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“…Our studies, therefore, provide in vivo evidence suggesting that exogenous PEDF supplementation may be a promising and plausible therapeutic modality for treatment and prevention of PH and chronic liver disease, at least in an early clinical setting. Of note, safety in humans will be soon confirmed as the first clinical trial with virally delivered PEDF in patients with choroidal neovascularisation is ongoing29 and a phase I, open-label trial has been recently completed in patients with macular degeneration (Clinical Trials: NCT00109499). Furthermore, the potential therapeutic application for endogenous inhibitors of angiogenesis in PH and cirrhosis has been also highlighted in a recent study from our group using vasohibin-1 22…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats

Mejías

Coch

Berzigotti

et al. 2014

Gut

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats

Mejías

Coch

Berzigotti

et al. 2014

Gut

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“…In a phase I study, patients with neovascular AMD were given a single intravitreous injection of an adenoviral vector expressing human PEDF; there was no increase in lesion size in the high-dose group 46. A further study showed that subconjunctival administration of recombinant human PEDF in murine models decreased laser-induced CNV lesions 47.…”

Section: Pigment Epithelium-derived Factormentioning

confidence: 99%

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

Dias¹,

Rodrigues

Maia

et al. 2011

British Journal of Ophthalmology

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The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

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“…A partially deleted adenoviral vector carrying PEDF (Ad-PEDF.11) also inhibits CNV in three different murine models26 and a pig model27 of CNV. A dose-related inflammatory response was observed for Ad-PEDF.11 in cynomolgus monkeys,28 but the safety of this vector for the treatment of neovascular AMD has been demonstrated in a phase 1 clinical trial 79…”

Section: Ocular Gene Therapy In Experimental Modelsmentioning

confidence: 99%

Gene therapy for ocular diseases

Liu

Tuo

Chan

2010

British Journal of Ophthalmology

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The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

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Adenoviral Vector-Delivered Pigment Epithelium-Derived Factor for Neovascular Age-Related Macular Degeneration: Results of a Phase I Clinical Trial

Cited by 49 publications

References 8 publications

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

Gene therapy for ocular diseases

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