The future use of complement inhibitors for the treatment of neurological diseases.
A chronically activated immune system can kill host cells, and accumulating evidence suggests that this mechanism plays an important role in many degenerative diseases. It may be of importance in CNS conditions such as Alzheimer's disease, ischaemia and even Parkinson's disease, as well as in peripheral disorders such as myocardial ischaemia and xenotransplantation. The complement system plays a key role in the immune reaction and can kill host tissue directly, by action of the membrane attack complex (MAC) of complement, or indirectly, through activation of macrophages which produce abundant amounts of oxygen radicals and other potentially toxic products. Endogenous regulators for many steps in the complement cascade have been identified, and these and some analogues are being explored as possible agents for the prevention of the toxic effects of complement activation. Numerous reports have attested to the protective effects of such inhibitors in animal models of immune disorders, particularly of transplant rejection and ischaemia-reperfusion injury. There have been a few clinical trials in peripheral disorders and, although not yet tried in neurological disease, it seems probable that this general approach will lead to therapeutic agents capable of specific modulation of the central immune response.
McGeer
E G
EG
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada. mcgeerpl@unixg.ubc.ca
McGeer
P L
PL
D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects*; D003169:Complement Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016377:Organ Transplantation; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology
D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex