Smith-Lemli-Optiz syndrome (SLOS) is a rare single-gene disorder that causes multiple congenital malformations, impaired cognitive function and behaviors of the autism spectrum disorder.
Previously, Vanderbilt scientists found that mutations in the gene encoding the last enzyme in cholesterol biosynthesis (which cause SLOS) result in accumulation of 7-dehydrocholesterol (7-DHC) – a reactive lipid that, through peroxidation, produces oxidation products capable of killing cells and altering gene expression.
In the Feb. 1 issue of Biological Psychiatry, Zeljka Korade, Ph.D., Ned A. Porter, Ph.D., and colleagues report that antioxidants, specifically vitamin E supplementation, effectively inhibit 7-DHC peroxidation in fibroblasts (connective tissue cells) from SLOS patients and in a mouse model of the disease, thus preventing buildup of damaging oxidation products.
Antioxidant/vitamin E supplementation in SLOS patients is not recommended at this time, however, because further studies are required to confirm these results and high concentrations of antioxidants can cause potentially serious side effects, the authors warned. Pursuing these findings, however, could “ultimately help guide future therapeutic developments,” they concluded.
The research was supported by National Institutes of Health grants HD073270, AG038739, MH079299, MH067234 and HD064727.
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