Perspective abstract
Nature Biotechnology 25, 1256 - 1264 (2007)
Published online: 7 November 2007 | doi:10.1038/nbt1344
There is an Erratum (December 2007) associated with this Perspective.
Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria
Russell P Rother1, Scott A Rollins1, Christopher F Mojcik1, Robert A Brodsky2 & Leonard Bell1
Abstract
The complement system provides critical immunoprotective and immunoregulatory functions but uncontrolled complement activation can lead to severe pathology. In the rare hemolytic disease paroxysmal nocturnal hemoglobinuria (PNH), somatic mutations result in a deficiency of glycosylphosphatidylinositol-linked surface proteins, including the terminal complement inhibitor CD59, on hematopoietic stem cells. In a dysfunctional bone marrow background, these mutated progenitor blood cells expand and populate the periphery. Deficiency of CD59 on PNH red blood cells results in chronic complement-mediated intravascular hemolysis, a process central to the morbidity and mortality of PNH. A recently developed, humanized monoclonal antibody directed against complement component C5, eculizumab (Soliris; Alexion Pharmaceuticals Inc., Cheshire, CT, USA), blocks the proinflammatory and cytolytic effects of terminal complement activation. The recent approval of eculizumab as a first-in-class complement inhibitor for the treatment of PNH validates the concept of complement inhibition as an effective therapy and provides rationale for investigation of other indications in which complement plays a role.
- Alexion Pharmaceuticals, Inc., 352 Knotter Drive, Cheshire, Connecticut 06410, USA.
- Johns Hopkins University School of Medicine, Division of Hematology, 720 Rutland Avenue, Ross Building Room 1025, Baltimore, Maryland 21205, USA.
Correspondence to: Russell P Rother1 e-mail: rotherr@alxn.com
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Thrombotic microangiopathy Can liver?kidney transplantation cure aHUS?Nature Reviews Nephrology News and Views (01 Oct 2009)
RESEARCH
Analysis of the promoters and 5′-UTR of mouse Cd59 genes, and of their functional activity in erythrocytesGenes and Immunity Original Article
Complement-targeted therapeuticsNature Biotechnology Research (01 Nov 2007)
Unrelated donor bone marrow transplantation with treosulfan-based myeloablative conditioning for paroxysmal nocturnal hemoglobinuria- successful treatment despite multiple transplant-related risk factors for hemolysis including major Kidd group incompatibilityBone Marrow Transplantation Letter
See all 30 matches for Research
