Effects of drugs on cholesterol esterification in normal and Niemann-Pick type C fibroblasts: AY-9944, other cationic amphiphilic drugs and DMSO.

AY-9944 and other cationic amphiphilic drugs (CADs) have been reported to cause a reduction of acid sphingomyelinase activity in fibroblasts and various tissues in the rat, and DMSO has been known to correct a partial deficiency of acid sphingomyelinase activity in Niemann-Pick type C (NPC) fibroblasts. Furthermore, in the present study we demonstrated that AY-9944 and other CADs caused a marked reduction of cholesterol esterification in control fibroblasts and an excessive intracellular accumulation of unesterified cholesterol as in NPC cells, and that this reduction could partially be corrected by the addition of 2% DMSO to the medium. These characteristics of the drug-treated cells mimic the phenomena seen in NPC fibroblasts. Therefore, fibroblasts treated with CADs may be used as a model of drug-induced lipidosis of NPC. The effect of DMSO suggests the possibility of its usefulness in the treatment of NPC patients.