Complement C3-targeted therapy: replacing long-held assertions with evidence-based discovery

    • Complement dysregulation underlies several inflammatory disorders, and terminal complement inhibition has thus far afforded significant clinical gains.
    • Emerging pathologies, fueled by complement imbalance and therapy-skewing genetic variance, underscore the need for more comprehensive, disease-tailored interventions.
    • Modulation at the level of C3, a multifaceted orchestrator of the complement cascade, opens up prospects for broader therapeutic efficacy by targeting multiple pathogenic pathways modulated by C3-triggered proinflammatory crosstalk.
    • Notably, C3 intervention is emerging as a viable therapeutic strategy for renal disorders with predominantly complement-driven etiology, such as C3 glomerulopathy (C3G).
    • Conclusion: Using C3G as a paradigm, we argue that concerns about the feasibility of long-term C3 intervention need to be placed into perspective and weighed against actual therapeutic outcomes in prospective clinical trials.
Author and source information

Authors: Mastellos DC, Reis ES, Ricklin D, Smith RJ, Lambris JD.
Reference: Trends Immunol. 2017 Jun;38(6):383-394. doi: 10.1016/ Epub 2017 Apr 14.