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Nat Rev Nephrol. 2018 Jan;14(1):26-47. doi: 10.1038/nrneph.2017.156. Epub 2017 Dec 4.

The renaissance of complement therapeutics.

Author information

1
Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
2
National Center for Scientific Research 'Demokritos', Patr. Gregoriou E & 27 Neapoleos Str, 15341 Agia Paraskevi, Athens, Greece.
3
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 401 Stellar Chance, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.

Abstract

The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.

PMID:
29199277
PMCID:
PMC5805379
DOI:
10.1038/nrneph.2017.156
[Indexed for MEDLINE]
Free PMC Article

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