Gene Therapy Successful in Halting CNV

by Dan Roberts
Researchers have been able to halt (at least temporarily) choroidal neovascularization (CNV) with gene replacement therapy. This was done by single injections into the eyeballs of patients during a phase I clinical trial. Here is more detail, as reported on January 17, 2006 by Genetic Engineering News (
Clinical Trial on Gene Therapy for Macular Degeneration Published in Human Gene Therapy
An adenoviral-based vector containing the gene for human pigment epithelium-derived factor (PEDF) showed evidence of being able to stop disease progression when injected directly into the eyes of patients with neovascular age-related macular degeneration, according to the results of a phase I clinical trial to be published in the February 2006 issue (Volume 17, Number 2) of Human Gene Therapy.
These promising results suggest that adenoviral vector-mediated ocular gene transfer represents a viable approach to treating ocular disorders such as age-related macular degeneration (AMD), which is one of the most common causes of severe vision loss.
Peter Campochiaro, M.D., Professor of Ophthalmology and Neuroscience, and Co-director of Vitreoretinal Surgery at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine (Baltimore, MD), and colleagues report on the use of a single intravitreous gene therapy injection in 28 patients with advanced neovascular AMD in a paper entitled, “Adenoviral Vector-Delivered Pigment Epithelium-Derived Factor for Neovascular Age-Related Macular Degeneration: Results of a Phase I Clinical Trial.”
AMD is a complex disorder characterized by the death of photoreceptors and retinal pigmented epithelial cells, caused in part by the growth of new blood vessels (angiogenesis) in the eye and the resulting leakage of plasma that form pockets of fluid around the retina. Visual loss is still reversible at this stage of disease if the angiogenic process can be stopped and fluid resorption takes place.
Injections of low and high doses of the adenoviral-PEDF vector caused no serious adverse effects in these patients. Although the therapy yielded no improvement (decrease) in the median lesion size from baseline, in the group that received high-dose gene therapy the lesions showed no increase in size at 6 and 12 months post-injection, compared to a median increase in lesion size of 0.5 and 1.0 disc area, respectively, in the low-dose group. This suggests that therapy was able to at least temporarily halt the natural progression of angiogenesis in neovascular AMD.
“It is encouraging that evidence of a sustained therapeutic effect was seen…after one intravitreal injection,” writes Jean Bennett, M.D., Ph.D., Professor of Ophthalmology, Cell and Developmental Biology, at the University of Pennsylvania School of Medicine (Philadelphia), in an accompanying Commentary in the February issue of the Journal. “The results from the Campochiaro et al. study are extremely encouraging as there were no serious adverse events or dose-limiting toxicities through the highest dose.”