Angiogenesis, the formation of new blood vessels, is implicated in the onset of a wide range of diseases such as age-related macular degeneration, corneal neovascularization and cancer. At least 184 million patients in Western nations could benefit from some form of antiangiogenic therapy, which makes it one of the most heavily invested areas of medical research. Natural antiangiogenic factors have been considered as potential therapeutic agents, although their exact physiological functions remain largely unexplored. The present technology deals with novel molecules that can be utilized to develop efficient antiangiogenic drugs for use in retinopathies and malignancies.
· Antitumor agent for the treatment of solid tumor malignancies.
· Therapeutic agent for various eye disorders such as diabetic retinopathy, age-related macular degeneration, and corneal neovascularization.
· Treatment of other angiogenesis-dependent diseases.
· Strong efficacy was demonstrated in animal models of breast cancer
· Synergistic effect to Avastin was demonstrated in animal models which supports the different mechanisms of the two compounds
· Because PEDF is a molecule that is widely expressed in the body, it seems unlikely that its therapeutic administration elicits major toxic effects in the body.
· Unlike most other compounds with antiangiogenic properties, PEDF also harbors direct antitumor activities such as induction of differentiation or apopotosis in tumor cells.
Pigment epithelium derived factor (PEDF) is a major potent natural antiangiogenic factor that was initially identified in the mammalian eye, where it plays a crucial role in retinal angiogenesis. It is also widely expressed in other body regions, including the plasma. Phosphorylation of PEDF plays an important role in the determination of its physiologic activity. The present invention relates to mutant forms of PEDF that mimic its phosphorylated state which posses a marked elevation in its antiangiogenic activity both in vitro and in vivo.