ANTI-AMYLOID DRUGS - POTENTIAL IN THE TREATMENT OF DISEASES ASSOCIATED WITH AGING

The requirements for amyloidogenesis, as it is currently understood, i nclude an adequate amyloid precursor pool, a nidus for fibrillogenesis , interactions with a set of common components (most of which are invo lved in basement membrane structure) and amyloid turnover. These facto rs serve as the basis for therapeutic attack. General strategies focus ing on each of these factors are presented with examples from the expe rimental and clinical literature. These include reducing the amyloid p recursor protein pool in familial amyloid polyneuropathy by liver tran splantation, inhibiting nidus formation in familial Mediterranean feve r by the use of colchicine, inhibiting amyloid precursor protein/hepar an sulphate interaction in experimental inflammation-associated amyloi dosis by the use of novel small molecule anionic sulphates and sulphon ates, and the use of new analogues of doxorubicin in light chain amylo idosis to accelerate amyloid removal. The potential significance of lo cal and systemic amyloid deposits is discussed in the light of new inf ormation on the genetics of Alzheimer's disease, observations made in patients receiving long term dialysis for renal failure, and the poten tial involvement of amyloid deposits in the pathogenesis of non-insuli n-dependent diabetes mellitus.