Drugs such as statins can reduce high plasma levels of the low-density lipoprotein (LDL) cholesterol that is a significant risk factor for atherosclerosis. In December Nature Medicine Thierry Grand-Perret and colleagues from GlaxoSmithKline, France showed that compounds that bind directly to the sterol regulating protein SCAP, could lower cholesterol levels via a mechanism other than that employed by the statins.

Grand-Perret et al. administered SCAP ligands to hyperlipidemic hamsters and found that these compounds increased LDL receptor mRNA molecules in the liver and reduced both LDL cholesterol and triglyceride levels by up to 80%. In addition, they used human hepatoma cells to confirm that SCAP ligants act through the sterol-responsive element of the LDLr promoter and activate the SCAP/SREBP pathway, leading to increase LDLr expression and activity, even in the presence of excess of sterols (Nat Med 2001, 7:1332-1338).

"Further elucidation of the molecular pathways that...