Applying complement therapeutics to rare diseases.
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.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edimara S
ES
Reis
Division of Biodiagnostic Sciences and Technologies, INRASTES, National Center for Scientific Research 'Demokritos', Athens, Greece.
Dimitrios C
DC
Mastellos
Amyndas Pharmaceuticals, Glyfada, Greece.
Despina
D
Yancopoulou
Hematology Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
Antonio M
AM
Risitano
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Daniel
D
Ricklin
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: lambris@upenn.edu.
John D
JD
Lambris
D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D003167:Complement Activation / Q000187:drug effects* / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006457:Hemoglobinuria, Paroxysmal / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D035583:Rare Diseases / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D003165:Complement System Proteins; C481642:eculizumab
Autoimmune diseases; C1 inhibitor; Complement; Compstatin; Eculizumab; Orphan drugs; Rare diseases