Effect of Clodronate on the Pathogenesis in a Mouse Model of Lysosomal Acid Lipase Deficiency.

Lysosomal acid lipase deficiency (LAL-D, OMIM #309900), caused by mutations of the LIPA gene, is involved in two continuum disease phenotypes: Wolman disease in infants and cholesteryl ester storage disease in adults. Their major phenotypes include steatosis, hepatomegaly, splenomegaly, and elevated liver enzymes. Enzyme replacement therapy has been used for the treatment of LAL-D. In this study, we examined the therapeutic effect of liposomal clodronate in an LAL-D mouse model. When liposomal clodronate was administered intraperitoneally by a single administration at 200 mg/kg to adult mice, organ cholesterol and triglyceride levels partially decreased. Furthermore, a significant correction of the relative organ weight of the liver and spleen as well as a reduction in splenic lipids were observed when liposomal clodronate was administered at 50 mg/kg to young mice intraperitoneally by multiple administrations. These results demonstrate that liposomal clodronate might have a therapeutic effect on the LAL-D mouse model.