Complement, a target for therapy in inflammatory and degenerative diseases

Complement is a key component of immunity with crucial inflammatory and opsonic properties; inappropriate activation of complement triggers or exacerbates inflammatory disease.Complement dysregulation is a core feature of some diseases and contributes to pathology in many others.Approved agents have been developed for and are highly effective in some orphan applications, but their progress to use in more common diseases has been slow.Numerous challenges, such as target concentration or high turnover, limit the efficacy of these agents in humans.Numerous novel agents targeting different parts of the complement system in different ways are now emerging from pre-clinical studies and are entering Phase I/II trials; these agents bring the potential for more-effective and more-specific anti-complement therapies in disease.Other agents, both biologic and small molecule, are in Phase II or III trials for both rare and common diseases — administration routes include localized (for example, intravitreal) and systemic routes.There is an urgent need to develop biomarkers and imaging methods that enable monitoring of the effects and efficacy of anti-complement agents.