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.