Applying complement therapeutics to rare diseases

Clin Immunol. 2015 Dec;161(2):225-40. doi: 10.1016/j.clim.2015.08.009. Epub 2015 Sep 1.


Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis.

Keywords: Autoimmune diseases; C1 inhibitor; Complement; Compstatin; Eculizumab; Orphan drugs; Rare diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angioedemas, Hereditary / drug therapy*
  • Angioedemas, Hereditary / immunology
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Complement Activation / drug effects*
  • Complement Activation / immunology
  • Complement System Proteins / immunology
  • Hemoglobinuria, Paroxysmal / drug therapy*
  • Hemoglobinuria, Paroxysmal / immunology
  • Humans
  • Models, Immunological
  • Rare Diseases / drug therapy*
  • Rare Diseases / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Complement System Proteins
  • eculizumab