Statins for Smith-Lemli-Opitz syndrome

Abstract

have no known conflicts of interest to be disclosed. Simona Bianconi and Forbes D. Porter conducted and published the largest trial to date on statin therapy in SLOS patients: "A Placebo-Controlled Trial of Simvastatin Therapy in Smith-Lemli-Opitz Syndrome" (Wassif 2017). As a result, they will be excluded from evaluating the eligibility of that study for inclusion in our review, as well as their exclusion from any subsequent data handling pertaining to that study.

Bottlenecks in the Investigation of Retinal Sterol Homeostasis

“…While there are several known human hereditary diseases caused by cholesterol biosynthetic defects, they are all recessive and, thankfully, rare, and none of them are non-syndromic (i.e., all bodily tissues are affected, not specifically the retina) [ 2 , 84 ]. While pharmacological and dietary supplementation approaches have been tried as therapeutic interventions for clinical management of patients afflicted with such diseases, in general, those approaches have not proven to be widely effective [ 85 , 86 , 87 , 88 ]. With regard to human diseases that involve disruption of cholesterol homeostasis that involve structural and/or functional abnormalities in the retina, it is more often the case of having too much cholesterol (and its esters and oxidized by-products), i.e., deposition and failure to efficiently remove excess cholesterol-rich deposits, rather than local defective de novo synthesis of cholesterol [ 89 , 90 ].…”

Smith-Lemli-Opitz syndrome: Bosnian and Herzegovinian experience

“…However, based on the underlying biochemistry and empirical data, cholesterol supplementation is the usual treatment, but with limited benefits due to the inability of cholesterol to cross the blood-brain barrier. Moreover, supplemental antioxidants, fat-soluble vitamins and coenzyme Q10 are given to these patients [ 6 ]. Statins, pharmacological inhibitors of enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are potentially promising candidates for therapy of SLOS, but data are still insufficient.…”

Metabolic Control of Sensory Neuron Survival by the p75 Neurotrophin Receptor in Schwann Cells

“…Smith-Lemli-Opitz syndrome (SLOS) is another example of cholesterol pathway disruption leading to neurological dysfunction. Although peripheral neuropathy in SLOS is much rarer than in TD, polyneuropathy with demyelinating features has been noted in several patients with SLOS (Starck et al, 2007;Ballout et al, 2020). Unlike the previously listed sterol disorders, SLOS results not from impaired sterol trafficking but a defective cholesterol biosynthetic pathway.…”

“…Accordingly, 7-DHC derived oxysterols have been shown to be highly cytotoxic to both Neuro2a cells and cortical neurons, (Xu et al, 2012b). However, while peripheral neuropathy has been noted in several patients with SLOS (Starck et al, 2007;Ballout et al, 2020), the effects 7-DHC on peripheral sensory neurons to our knowledge have never been examined. Therefore, we treated cultured rat DRG neurons were with 7-DHC and the number of live neurofilament + neurons were quantified after 3 days.…”