OCU200 (Tumstatin-Transferrin) as a Treatment for Neovascular Disorders
OCU200 is a fusion protein that combines the anti-angiogenic properties of tumstatin with the targeting properties of transferrin. OCU200 down regulates angiogenesis in active endothelial cells involved in choroidal neovascularization by binding to αVβ3 integrins. The targeting element allows for efficient delivery of the molecule to the diseased tissue. OCU200 has shown a strong dose response effect in animal models of wet age-related macular degeneration and represents the initial target clinical indication for OCU200.
Tumstatin is an endogenous fragment of collagen IV and has been shown to be a powerful anti-angiogenic agent. Tumstatin plays a pivotal role in inhibiting blood vessel formation by binding to αVβ3 integrins. αVβ3 integrins are found on actively proliferating endothelial cells within the retina and are known to be directly involved in angiogenesis (Friedlander et al., Proc. Natl. Acad. Sci. USA Vol. 93, pp. 9764-9769, September 1996). Tumstatin binds to αVβ3 integrins on active endothelial cells and selectively stimulates an anti-angiogenic response (Maeshima Y, et al. J Biol Chem 275(28):21340-21348). This unique mechanism of action drives regression of endothelial cells and results in a VEGF independent treatment approach with the potential for true disease modification which currently does not exist.
Transferrin is an iron uptake protein and both transferrin and its receptor are highly expressed within the retina. Transferrin has been shown to facilitate macromolecule migration across a number of cell types including retinal pigment epithelial cells and the use of transferrin as a drug delivery agent has been established as a means for effective drug targeting within the retina.