Complement C3-Targeted Therapy:: Replacing Long-Held Assertions with Evidence-Based Discovery

• Autores: Dimitrios C. Mastellos, Edimara S. Reis, Daniel Ricklin, Richard J. Smith, John D. Lambris
• Localización: Trends in immunology, ISSN 1471-4906, Vol. 38, Nº. 6, 2017, págs. 383-394
• Idioma: inglés
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• Resumen

  • Complement dysregulation underlies several inflammatory disorders, and terminal complement inhibition has thus far afforded significant clinical gains. Nonetheless, 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). 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.