Targeting the complement cascade: novel treatments coming down the pike.
The complement cascade is a vital component of both the innate and adaptive immune systems. Complement activation also contributes to the pathogenesis of many diseases, however, and the kidney is particularly susceptible to complement-mediated injury. Drugs that block complement activation can rapidly reduce tissue inflammation and also attenuate the adaptive immune response to foreign and tissue antigens. Eculizumab is a monoclonal antibody that prevents the cleavage of C5. It has been approved for the treatment of atypical hemolytic uremic syndrome, and it has been used in selected patients with other kidney diseases. Many additional drugs are also in development for blocking the complement cascade, including new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Validation of these new drugs as effective treatments for kidney diseases faces several challenges. Many complement-mediated kidney diseases are rare, so it is not feasible to test all of the new drugs in numerous different rare diseases. The onset and course of the diseases are heterogeneous; many of these diseases also carry a lifelong risk of recurrence, and it is not clear how long complement inhibition must be maintained. In spite of these challenges, new therapeutic options for targeting the complement system will likely become available in the near future and may prove useful for treating patients with kidney disease.
Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA. Electronic address: Joshua.Thurman@ucdenver.edu.
Joshua M
JM
Thurman
Department of Nephrology and Renal Transplantation, Lapeyronnie Hospital and INSERM U1183, Institute of Regenerative Medicine and Biotherapies, Montpellier, France.
Moglie
M
Le Quintrec
D056704:Adaptive Immunity / Q000187:drug effects; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D002833:Choroiditis; D003167:Complement Activation / Q000187:drug effects*; D051056:Complement Inactivating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007668:Kidney / Q000276:immunology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology; D000080364:Multifocal Choroiditis; D012008:Recurrence
D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D003165:Complement System Proteins; C481642:eculizumab
complement; glomerulonephritis; inflammation