Targeting SDF-1 for effective wet AMD treatment

PROJECT ABSTRACT Wet Age related Macular DegenerationAMDis the leading cause of new blindness among people who areor olderThe current standard of care for wet AMD is anti Vascular Endothelial Growth FactorVEGFagentssuch as LucentisEyleaand Avastinused off labelThese anti VEGF agents inhibit VEGF mediated angiogenesisand effectively stop or even reverse the vision loss for most patientsDespite being the best treatment currently availableit has two critical shortcomingslimited near term vision gain and poor longterm vision maintenancemajor cost and treatment burdenFirstdespite continued treatmentonlyof the patient gain andgtlines of vision over the firstmonthsafteryearsmost patients start losing vision again and eventually dropping to pre treatment levelsSecondpatients must return to the clinic everytomonths for intravitreal injectionsa specializeduncomfortable and costly procedure that represents significant treatment burdenThe purpose of this SBIR is to develop highly stable aptamers against SDFwhich may serve as an orthogonal treatment for wet AMDSDFhas long been known to play an important role in choroidal neovascularizationCNVthe landmark pathological process of wet AMDThe Aptitude team has accumulated extensive experience in aptamer discoveryWe have previously developed the Particle Display method that significantly improves the aptamer performanceMoreoverwe have made further improvement to directly screen for fully modified aptamers that enables longer duration of efficacyOur expertise in aptamer discovery is complemented by our collaboratorsexpertise in wet AMD preclinical researchOur collaborator is among the first to demonstrate the role of SDFin CNVand possess in depth expertise in relevant animal modelsIf successfulthis project has the potential of bringing more efficacious and affordable treatment to wet AMD patients NARRATIVE Wet Age related Macular Degenerationwet AMDis the leading cause of new blindness among people who areor olderAnti VEGF therapeutics such as Eylea and Lucentis are the standard treatment and are effective in improving vision in the near termHoweverthe vision gain typically plateaus soonand patients will later start to lose vision again despite continued treatmentWe propose to create a highly stable aptamer that can target an orthogonal targetSDFthus providing synergistic effect to the current treatment or offering potential alternative treatments for patients who donandapos t respond well to the anti VEGF agents!