Therapeutic inhibition of the complement system.
The use of powerful methodologies in molecular biology, biochemistry, and physiology in the last 2 decades had led to impressive progress in our understanding of the mechanisms of complement activation and its role as either a protective or a pathogenic factor in human disease. With respect to disease pathogenesis, the complexity of the complement cascade provides opportunities for several different therapeutic targets within the complement pathways. More than a century after complement was first described, we are about to witness in the near future the availability of a variety of complement inhibitors for specific therapies. Progress in the area of xenotransplantation has been substantial, but formidable obstacles remain to selective inhibition of the factors that block successful clinical xenotransplantation. Bispecific antibodies, designed to enhance rather than inhibit existing complement pathways, hold strong promise for the clearance of viral and bacterial pathogens from the circulation.
Makrides
S C
SC
Department of Cell Biology, PRAECIS Pharmaceuticals, Inc., Cambridge, MA 02139-1572, USA.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D018958:CD55 Antigens / Q000187:drug effects / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000502:physiology; D003171:Complement Pathway, Classical / Q000502:physiology; D003165:Complement System Proteins / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D014183:Transplantation, Heterologous
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010455:Peptides; D011951:Receptors, Complement; D003165:Complement System Proteins