Applying complement therapeutics to rare diseases.

Abstract

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.

• Authors: Edimara S Reis, Dimitrios C Mastellos, Despina Yancopoulou, Antonio M Risitano, Daniel Ricklin, John D Lambris
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 161 Issue 2 Pg. 225-40 (Dec 2015) ISSN: 1521-7035 [Electronic] United States
• PMID: 26341313 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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