Exudative age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR), due to aberrant choroidal and retinal neovascularization respectively, are two of the leading major causes of blindness in the US. PEDF (Pigment Epithelium-Derived Factor) is a potent endogenous antiangiogenic/neurotrophic factor and is purported to be the key natural regulator of vascularity in the eye. In experimental disease models, PEDF blocks choroidal and retinal neovascularization. Based on these compelling data, we hypothesize that administration of PEDF protein may treat blinding ocular neovascular diseases such as wet AMD. It will be the overall goal of the SBIR Phase II to generate preclinical data enabling potential clinical testing of PEDF protein. In this Phase I application, we will test the feasibility of generating PEDF for preclinical studies. We propose: 1) to generate reproducible stocks of high quality PEDF protein and 2) to demonstrate the biological activity/potency of the purified protein product. This bioactive recombinant human PEDF will be used for future PEDF pharmacokinetic studies, to test efficacy of purified PEDF protein in ocular disease models, to test various delivery approaches, and to determine whether PEDF-based product should be advanced to clinical testing. Furthermore, the methods and procedures generated in the Phase I SBIR grant may lead to future viable manufacturing processes and assays that could lead to clinical grade material.
