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Complement in human disease: approved and up-and-coming therapeutics. | LitMetric

Complement in human disease: approved and up-and-coming therapeutics.

Lancet

Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Published: January 2024

AI Article Synopsis

  • The complement system plays a vital role in defending against blood-borne pathogens and maintaining immune balance, but its dysregulation can lead to harmful inflammation and various autoimmune diseases.
  • Despite historically low approval rates for complement-targeting drugs, the success of eculizumab—a humanized anti-C5 antibody—has renewed interest in developing complement therapies.
  • Advances in understanding complement biology and drug discovery technologies are leading to a growing pipeline of potential treatments, with hopes of expanding their use beyond rare diseases to more common conditions.

Article Abstract

The complement system is recognised as a protector against blood-borne pathogens and a controller of immune system and tissue homoeostasis. However, dysregulated complement activity is associated with unwanted or non-resolving immune responses and inflammation, which induce or exacerbate the pathogenesis of a broad range of inflammatory and autoimmune diseases. Although the merit of targeting complement clinically has long been acknowledged, the overall complement drug approval rate has been modest. However, the success of the humanised anti-C5 antibody eculizumab in effectively treating paroxysmal nocturnal haemoglobinuria and atypical haemolytic syndrome has revitalised efforts to target complement therapeutically. Increased understanding of complement biology has led to the identification of novel targets for drug development that, in combination with advances in drug discovery and development technologies, has resulted in a surge of interest in bringing new complement therapeutics into clinical use. The rising number of approved drugs still almost exclusively target rare diseases, but the substantial pipeline of up-and-coming treatment options will possibly provide opportunities to also expand the clinical targeting of complement to common diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872502PMC
http://dx.doi.org/10.1016/S0140-6736(23)01524-6DOI Listing

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