Complement Inhibitors for Macular Degeneration

描述(由申请人提供)：老年性黄斑变性(AMD)在美国影响着近1000万人(预防失明研究基金会)。最近批准的抗血管内皮生长因子治疗是目前湿性AMD的唯一治愈方法。最近的研究证实了替代途径(AP)在AMD中的作用。渐进性失明最终导致失明是成人AMD的主要症状。利用小鼠AMD模型，Bora等人证明了替代途径中的补体因子B在疾病中发挥着重要作用。通过使用siRNA技术，博拉博士证明了B因子基因的沉默可以阻止AMD的诱导和持续。受到这些结果的鼓舞，我们决定评估我们的封闭性抗B因子单抗(Bikaciomab)在抑制AMD的发展和进展方面的效果。Bikaciomab结合人血中的B因子蛋白，阻断其在AP介导的补体激活中的作用。Bikaciomab可防止C3a、C5a和C5b-9的形成，C3a、C5a和C5b-9是导致炎症反应的关键过敏毒素。我们将测试这种封闭的抗B因子抗体在预防和建立疾病模型中的效果，以提供接受测试的药物的直接临床相关性。公共卫生相关性：老年性黄斑变性(AMD)在美国影响着近1000万人(预防失明研究基金会)。最近批准的抗血管内皮生长因子治疗是目前湿性AMD的唯一治愈方法。在黄斑变性领域有一个未得到满足的医疗需求。NovelMed目前的方法专注于中和B因子的功能并提供疾病益处。利用之前开发的AMD动物模型，NovelMed打算测试其治疗AMD的铅补体抑制剂。Bikaciomab在体外、体外和体内的强大活性使该药物不仅可用于治疗AMD，还可用于多种疾病的治疗，这些疾病的替代途径在疾病病理中发挥着重要作用。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) affects nearly 10 million people in the U.S (Research to Prevent Blindness Foundation). Recently approved anti-VEGF therapy is the only cure for wet AMD as of today. Recent studies have demonstrated the role of the alternative pathway (AP) in AMD. Gradual loss of vision eventually resulting in blindness is the key symptom of AMD in the adult population. Using the mouse AMD model, Bora et al demonstrated that complement factor B of the alternative pathway plays an important role in the disease. With the use of siRNA techniques, Dr. Bora demonstrated that silencing of the factor B gene prevents the induction and persistence of AMD. Encouraged by these results, we decided to evaluate the effect of our blocking anti-factor B monoclonal antibody (Bikaciomab) in inhibiting the development and progression of AMD. Bikaciomab binds factor B protein in human blood and blocks its function in AP mediated complement activation. Bikaciomab prevents alternative pathway mediated formation of C3a, C5a, and C5b-9, the key anaphylatoxins responsible for the inflammatory responses. We will test the effect of this blocking anti-factor B antibody in prophylaxis and established models of the disease to provide direct clinical relevance of the drug under testing. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) affects nearly 10 million people in the U.S (Research to Prevent Blindness Foundation). Recently approved anti-VEGF therapy is the only cure for wet AMD as of today. There is an unmet medical need in the area of macular degeneration. NovelMed's current approach focuses on neutralizing factor B function and providing disease benefit. Using the previously developed animal models of AMD, NovelMed intends to test its lead complement inhibitor for the treatment of AMD. Potent activity of Bikaciomab in vitro, ex vivo and in vivo makes the drug as a potential therapeutic for not only AMD but also for several diseases where alternative pathway plays an important role in disease pathology.