CHOLESTEROL AND PLASMA-LIPID MODIFYING PATENTS

Cholesterol lowering by the 3-hydroxy-3-methylglutaryl co-enzyme A (HM G-CoA) reductase inhibitors (statins) has been shown to have significa nt effects on mortality due to coronary heart disease (CHD) in several trials reported over the last four or so years. However, it has long been recognised that hypercholesterolaemia is not the only dyslipidaem ia which can contribute to CHD. This article reviews patenting activit y over the past few years directed towards normalisation of the plasma lipid profile by mechanisms which do not involve modulation of choles terol synthesis. Such mechanisms might include lowering plasma triglyc eride or lipoprotein (a) [Lp(a)] or raising plasma high-density lipopr otein (HDL). Many claimed compounds appear to have effects in animal o r cell models, but do not have a defined molecular target. Of the mole cular targets defined, the peroxisome proliferator-activated receptors (PPARs) have great promise. Gene therapy is well-represented in the p atent claims, but many technical hurdles remain to be overcome before such treatments are routine. Strategies affecting cholesterol absorpti on, cholesteryl ester synthesis and hydrolysis and bile acid metabolis m are not covered.