Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery.
- Mastellos DC Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Biodiagnostic Sciences and Technologies, Institute of Nuclear and Radiological Sciences and Technology, Energy, and Safety (INRASTES), National Center for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece.
- Reis ES Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Ricklin D Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
- Smith RJ Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address: richard-smith@uiowa.edu.
- Lambris JD Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: lambris@upenn.edu.
- 2017-04-19
Published in:
- Trends in immunology. - 2017
AMY-101
C3 glomerulopathy
C3 inhibitors
anti-C5 therapy
clinical efficacy
compstatin
Animals
Antibodies, Blocking
Clinical Trials as Topic
Complement Activation
Complement C3
Evidence-Based Medicine
Glomerulonephritis, Membranous
Humans
Immune Complex Diseases
Inflammation
Models, Immunological
Molecular Targeted Therapy
English
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1016/j.it.2017.03.003
- PMID 28416449
- Persistent URL
- https://sonar.ch/global/documents/232385
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