THE FUTURE USE OF COMPLEMENT INHIBITORS FOR THE TREATMENT OF NEUROLOGICAL DISEASES

A chronically activated immune system can kill host cells, and accumul ating 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 xe notransplantation. The complement system plays a key role in the immun e reaction and can kill host tissue directly, by action of the membran e attack complex (MAC) of complement, or indirectly, through activatio n of macrophages which produce abundant amounts of oxygen radicals and other potentially toxic products. Endogenous regulators for many seep s in the complement cascade have been identified, and these and some a nalogues are being explored as possible agents for the prevention of t he toxic effects of complement activation. Numerous reports have attes ted to the protective effects of such inhibitors in animal models of i mmune disorders, particularly of transplant rejection and ischaemia-re perfusion injury. There have been a few clinical trials in peripheral disorders and, although not yet tried in neurological disease, it seem s probable that this general approach will lead to therapeutic agents capable of specific modulation of the central immune response.