DEVELOPMENT OF RANIBIZUMAB, AN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ANTIGEN BINDING FRAGMENT, AS THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Angiogenesis is a key aspect of the wet form of age-related neovascular(AMD), the leading cause of blindness in the elderly population. Substantial evidenceindicated that vascular endothelial growth factor (VEGF)-A is a major mediator of angio-genesis and vascular leakage in wet AMD. VEGF-A is the prototype member of a genefamily that includes also PlGF, VEGF-B, VEGF-C, VEGF-D and the orf virus-encodedVEGF-E. Several isoforms of VEGF-A can be generated due to alternative mRNA splicing.Various VEGF inhibitors have been clinically developed. Among these, ranibizumab is ahigh affinity recombinant Fab that neutralizes all isoforms of VEGF-A. The article brieflyreviews the biology of VEGF and then focuses on the path that led to clinical developmentof ranibizumab.