The pharmaceutical industry has been hotly pursuing ways to block the action of VEGF in people at risk of blindness and for other diseases as well, including cancer. Tumors often overproduce VEGF to stimulate blood vessel growth within tumors so that their fast-dividing cells are kept supplied with oxygen and other nutrients. 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.
Blocking VEGF in eye diseases has proved to be complicated, however. In addition to stimulating the growth of new blood vessels and mediating vascular permeability, the molecule also plays a critical function in maintaining the health of nerve cells and blood vessels in the retina, so disabling it too much can create unintended consequences within the eye's delicate tissues.
A New Approach
Last year, in another paper published in the Journal of Clinical Investigation, Friedlander and his colleagues showed that VEGF is critically important for maintaining healthy vision as well and that blocking it completely can kill the eye's light-sensing cells, actually causing severe vision loss. (Friedlander's lab has investigated a number of other, non-VEGF angiogenic pathways and has shown that combining antagonists of these pathways along with a VEGF antagonist can actually enhance anti-angiogenic activity when used as combination therapy.)
"Our collaborator, David Cheresh, and his lab observed that microRNAs could be used to target neovascularization at a point in the pathway 'downstream' of VEGF," said Peter Westenskow, PhD, a postdoctoral fellow at TSRI and first
|Contact: Mika Ono|
Scripps Research Institute