Targeting SDF for effective wet AMD treatment

PROJECT ABSTRACT Wet Age related Macular Degeneration AMD is the leading cause of new blindness among people who are or older The current standard of care for wet AMD is anti Vascular Endothelial Growth Factor VEGF agents such as Lucentis Eylea and Avastin used off label These anti VEGF agents inhibit VEGF mediated angiogenesis and effectively stop or even reverse the vision loss for most patients Despite being the best treatment currently available it has two critical shortcomings limited near term vision gain and poor long term vision maintenance major cost and treatment burden First despite continued treatment only of the patient gain andgt lines of vision over the first months after years most patients start losing vision again and eventually dropping to pre treatment levels Second patients must return to the clinic every to months for intravitreal injections a specialized uncomfortable and costly procedure that represents significant treatment burden The purpose of this SBIR is to develop highly stable aptamers against SDF which may serve as an orthogonal treatment for wet AMD SDF has long been known to play an important role in choroidal neovascularization CNV the landmark pathological process of wet AMD The Aptitude team has accumulated extensive experience in aptamer discovery We have previously developed the Particle Display method that significantly improves the aptamer performance Moreover we have made further improvement to directly screen for fully modified aptamers that enables longer duration of efficacy Our expertise in aptamer discovery is complemented by our collaborators expertise in wet AMD preclinical research Our collaborator is among the first to demonstrate the role of SDF in CNV and possess in depth expertise in relevant animal models If successful this project has the potential of bringing more efficacious and affordable treatment to wet AMD patients NARRATIVE Wet Age related Macular Degeneration wet AMD is the leading cause of new blindness among people who are or older Anti VEGF therapeutics such as Eylea and Lucentis are the standard treatment and are effective in improving vision in the near term However the vision gain typically plateaus soon and patients will later start to lose vision again despite continued treatment We propose to create a highly stable aptamer that can target an orthogonal target SDF thus providing synergistic effect to the current treatment or offering potential alternative treatments for patients who donandapos t respond well to the anti VEGF agents !