MAY 17, 2011
This review article discusses current treatments for age-related macular degeneration (AMD) and potential therapies under research and development. The author predicts that future AMD therapies will be based on biology identified through epigenetics and gene-based models, which could potentially yield preventive therapies.
The article summarizes current AMD therapies as centered around intravitreal injection of anti- VEGF (vascular epithelial growth factor) treatments RNA aptamer pegaptanib (Macugen), antibody fragment ranibizumab (Lucentis) and full-length antibody bevacizumab (Avastin). The author points out that optimal dosing of anti-VEGF agents is still being studied. The development of other drugs that block VEGF, such as soluble receptors and RNA-interfering agents, is also discussed. The article covers exploration of combination therapies using anti-VEGF drugs, corticosteroids and/or photodynamic therapy with verteporfin (Visudyne).
However, the author says the future may lie with therapies that can halt the process of AMD before the occurrence of exudative or atrophic changes and concomitant vision loss. The search for appropriate targets for such therapies has involved identifying single nucleotide polymorphisms (SNPs) in genes that are associated with the pathogenesis of AMD. In particular, U.S. studies have identified SNPs in complement-related genes, such as for complement factor H, which confer susceptibility to AMD. To that end, anti-complement therapies are being tested.
Another exciting area of research, according to the author, examines the role of Bruch's membrane in AMD. For example, knock-out mice deficient in the gene for lysyl oxidase-like protein 1 (LOX1-1), an enzyme essential to elastin polymer formation in Bruch's membrane, appear to have increased choroidal neovascularization after laser injury. Other research is centered on the use of neuroprotective agents, including monocyte chemoattractant protein-1 (MCP-1) inhibitors and HIV protease inhibitors, in combination with anti-VEGF therapies to prevent photoreceptor cell degeneration and improve vision outcomes in patients with neovascular disease. The author says neuroregeneration and stem cell therapy also show potential as AMD therapies.