Journal of Genetic Syndromes & Gene Therapy
Open Access
ISSN: ISSN: 2157-7412
ISSN: ISSN: 2157-7412
Zeljka Korade
University of Nebraska Medical Center, USA
Posters & Accepted Abstracts: J Genet Syndr Gene Ther
Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis characterized by diminished cholesterol and increased 7-dehydrocholesterol (7DHC) levels. 7DHC is highly reactive, giving rise to biologically active oxysterols. While there is no effective treatment for SLOS, different approaches are in the use to treat various aspects of the disease including antioxidant therapy, inhibition of cholesterol biosynthesis and dietary supplementation of cholesterol. Although there are some improvements cholesterol supplementation does not restore nervous system function. Previous therapeutic approaches concentrated on interfering with the cholesterol biosynthesis pathway and use of statins had limited effect because cholesterol in the nervous system is regulated independently from whole body cholesterol. Dietary cholesterol does not cross the blood-brain-barrier and statins, inhibitors of HmgCoA reductase, in addition to decreasing cholesterol levels, affect cellular signaling and some do not affect brain cholesterol levels because they do not cross blood-brain-barrier. Exogenous cholesterol supplementation does not restore normal cellular function in Dhcr7-ablated cell lines and cholesterol supplementation leads to no significant improvement in SLOS in humans. Thus, it appears that the accumulation of 7DHC and 7DHC-derived oxysterols (rather than cholesterol deficit) may be critical for development of SLOS pathophysiology. Establishing assays for the toxic compounds and understanding their fundamental neurobiology will shed light on SLOS and lead to therapies for this disorder. Novel therapeutic strategies will be presented and discussed.
Email: zeljka.korade@Vanderbilt.Edu