Abstract
Smith-Lemli-Opitz Syndrome (SLOS) is a recessive hereditary disease caused by an enzymatic defect in the biosynthesis of cholesterol. To date, the therapeutic standard of care for this disease has been cholesterol supplementation therapy. However, the efficacy of this treatment is extremely variable and, in many if not most cases, is poor. Results of studies using animal models of SLOS have suggested that cholesterol deficiencyand/or the aberrant accumulation of the immediate precursor of cholesterol (7-dehydrocholesterol (7DHC)), per se, may not be the sole culprits in the pathobiology of this disease. Rather, cytotoxic oxysterol by-products derived specifically from 7DHC are thought to be additional, significant, causative players in the disease mechanism. Based in large measure upon such studies, a recent clinical trial, comparing the therapeutic efficacyof cholesterol supplementation alone vs. combined cholesterol-antioxidant supplementation in SLOS patients, has provided extremely encouraging results that tend to both validate the proposed role of oxysterols in the pathobiology of SLOS as well as indicate an improved treatment for this and related diseases.