Age-related macular degeneration (AMD) is the leading cause of blindness for Americans 60 years of age and older. It is estimated that the prevalence of AMD in the US is as high as 9 million, with 1.8 million individuals already suffering severe loss of vision from advanced AMD. As the population ages, the prevalence of AMD will continue to grow. The loss of visual acuity seen in even milder cases of AMD has a major impact on the quality of life as well as causing a significant economic burden to society. Studies on the pathogenesis of AMD have indicated that inflammation is a fundamental component of the disease. Furthermore, recent genetic evidence has strongly implicated a polymorphism in the complement control protein factor H as a major risk factor for the disease. Thus, it has been proposed that inadequate control of complement-driven inflammation may be a major factor in disease pathogenesis and that manipulation of the complement system may provide novel and promising therapeutic approaches to the treatment of AMD. This SBIR proposal will examine the potential therapeutic benefit of inhibition of the alternative pathway of complement activation in a constant-light exposure animal model of AMD. Inhibition of complement activation will be attained with a monoclonal Ab to the factor B component of the alternative pathway which has been licensed by Taligen Therapeutics, Inc. Recent studies by Dr. Michael Holers, Chief Scientific Officer of Taligen, in collaboration other investigators have demonstrated a critical role for factor B in driving inflammation in animal models of a number of diseases including asthma, ischemia-reperfusion injury, immunologic renal disease, post traumatic brain and spinal cord injury. In collaboration with Drs. Baerbel Roher and Gary Gilkeson at MUSC, we have obtained preliminary data to show that this antibody has a protective effect and a murine model of AMD. The Specific Aims of this proposal are to extend our preliminary observations to examine the effects of treatment with anti-factor B on retinal function and histology in an albino rat constant-light exposure model of AMD. Successful demonstration of a protective effect of this antibody will lead the company to initiate a full pre-clinical program (efficacy in larger animals, toxicology and pharmacokinetics) of this the antibody as a therapeutic for human AMD
