Statins in Membrane Lipid Therapy: Mechanistic Promise Versus Clinical Reality

Statins are widely used to inhibit cholesterol synthesis and help prevent cardiovascular diseases associated with elevated blood cholesterol levels. Several clinical trials have shown that some of the benefits observed with statins are independent of cholesterol lowering. Part of these pleiotropic effects is related to the ability of statins to directly interact with and alter the physical properties of lipid membranes such as lipid packing and, consequently, membrane fluidity. Membrane lipid therapy is an innovative approach based on the use of drugs with the potential to change membrane lipid structure for therapeutic purposes, including enhancing the intracellular delivery of chemotherapeutic drugs. Evidence from studies using both artificial model membranes and biological membranes supports the potential use of statins as effective drug candidates for membrane lipid therapy. However, the transition from the promising in vitro results to the clinical practice has encountered significant challenges. This commentary highlights the pitfalls in repurposing statins as membrane-modifying agents.