41.
Anti-VEGF: Developments, Comparison, New Drugs
Salvatore Grisanti (Lübeck)
In the field of age-related macular degeneration (AMD) the treatment philosophy is shifting
from a destructive to a more disease modulating strategy. Current approaches and developing
treatments for choroidal neovascularization are based on a growing understanding of the
molecular mechanisms of angiogenesis. After the exciting introduction of drugs sequestering
vascular endothelial cell growth factor (VEGF), one of the major players of angiogenesis, the
next decade promises to be as exciting as the previous one. Numerous new treatments with differing
mechanisms of action are currently under development. These include beside the inhibition
of free VEGF, such as with the VEGF trap, also the blockade of the intracellular signalling
pathway with inhibitors of tyrosine kinases or the silencing of contributing genes using small
interfering RNA.
Whether inhibition of the VEGF signalling alone is sufficient to targe the different stages of the
disease is under debate. Combined targeting of other factors, e. g. platelet-derived growth factor B (PDGF-B) that is essential
for pericyte recruitment may have a synergistic effect by sensitizing the vasculature to the effects of anti-VEGF therapy.
Future interventions may also include gene therapy with adenoviral vectors to up-regulate natural inhibitors of endothelial
angiogenesis such as pigment epithelium-derived factor (PEDF).
The effective approach in the future treatment of exsudative AMD will combine and titrate different strategies targeting
endothelial cell proliferation, extracellular matrix proteins, vessel wall modelling and endothelial cell survival as well.