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Nat Rev Drug Discov. 2019 Jul 19. doi: 10.1038/s41573-019-0031-6. [Epub ahead of print]

Clinical promise of next-generation complement therapeutics.

Author information

1
National Center for Scientific Research 'Demokritos', Athens, Greece.
2
Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
3
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. lambris@pennmedicine.upenn.edu.

Abstract

The complement system plays a key role in pathogen immunosurveillance and tissue homeostasis. However, subversion of its tight regulatory control can fuel a vicious cycle of inflammatory damage that exacerbates pathology. The clinical merit of targeting the complement system has been established for rare clinical disorders such as paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome. Evidence from preclinical studies and human genome-wide analyses, supported by new molecular and structural insights, has revealed new pathomechanisms and unmet clinical needs that have thrust a new generation of complement inhibitors into clinical development for a variety of indications. This review critically discusses recent clinical milestones in complement drug discovery, providing an updated translational perspective that may guide optimal target selection and disease-tailored complement intervention.

PMID:
31324874
DOI:
10.1038/s41573-019-0031-6

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