Study calls for caution, further studies on drugs tsed to treat macular degeneration news
30 October 2012

Millions of people with ''wet'' macular degeneration are prescribed a class of medication known as anti-VEGF drugs. But now scientists at The Scripps Research Institute (TSRI) have found that a drastic reduction of VEGF activity may do more harm than good.

In the new study, the researchers deleted the gene for the blood-vessel growth factor VEGF, which has been implicated in stimulating abnormal blood vessel growth in a range of cancers and eye diseases, from cells in the retinas of adult mice. The results showed that without VEGF a large subset of light-sensing cells lost their main blood supply and shut down, causing severe vision loss.

''It's becoming clear that VEGF has a critical function in maintaining the health of the retina, and we need to preserve that critical function when we treat VEGF-related conditions,'' said TSRI Professor Martin Friedlander, MD, PhD, senior author of the new study, which appears in the November 2012 issue of the Journal of Clinical Investigation.

Major target for drug developers
VEGF (vascular endothelial growth factor) has long been a major target for drug developers. Tumours often overproduce VEGF to stimulate local blood vessel growth and thus keep their fast-dividing cells well supplied with oxygen and nutrients. Low-oxygen conditions in the eyes of elderly or diabetic individuals also can trigger the overproduction of VEGF, resulting in a vision-destroying bloom of abnormal, leaky retinal blood vessels.

Several anti-VEGF drugs (such as Lucentis (ranibizumab), Macugen (pegaptanib), Eylea (aflibercept) and Avastin (bevacizumab)) are already in use, and dozens more are in clinical trials against cancers and common eye disorders such as wet macular degeneration.

However, to date there have not been extensive studies on the effects of such drugs on the normal role of VEGF, in part because it is hard to generate adult animals that lack the VEGF gene. When the gene is removed from the embryos of mice, in a standard ''knockout'' experiment, the mice fail to develop normally and die before birth.

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Study calls for caution, further studies on drugs tsed to treat macular degeneration