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A placebo-controlled trial of simvastatin therapy in Smith-Lemli-Opitz syndrome
- Source :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/cognitive impairment syndrome characterized by the accumulation of 7-dehydrocholesterol, a precursor sterol of cholesterol. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor that crosses the blood–brain barrier, has been proposed for the treatment of SLOS based on in vitro and in vivo studies suggesting that simvastatin increases the expression of hypomorphic DHCR7 alleles. Safety and efficacy of simvastatin therapy in 23 patients with mild to typical SLOS were evaluated in a randomized, double-blind, placebo-controlled trial. The crossover trial consisted of two 12-month treatment phases separated by a 2-month washout period. No safety issues were identified in this study. Plasma dehydrocholesterol concentrations decreased significantly: 8.9 ± 8.4% on placebo to 6.1 ± 5.5% on simvastatin (P < 0.005); we observed a trend toward decreased cerebrospinal fluid dehydrocholesterol concentrations. A significant improvement (P = 0.017, paired t-test) was observed on the irritability subscale of the Aberrant Behavior Checklist–C when subjects were taking simvastatin. This article reports what is, to our knowledge, the first randomized, placebo-controlled trial designed to test the safety and efficacy of simvastatin therapy in SLOS. Simvastatin seems to be relatively safe in patients with SLOS, improves the serum dehydrocholesterol–to–total sterol ratio, and significantly improves irritability symptoms in patients with mild to classic SLOS. Genet Med 19 3, 297–305.
- Subjects :
- Male
0301 basic medicine
Oxidoreductases Acting on CH-CH Group Donors
Simvastatin
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Adolescent
Placebo-controlled study
Irritability
Placebo
Gastroenterology
Article
law.invention
Placebos
03 medical and health sciences
chemistry.chemical_compound
Dehydrocholesterols
Double-Blind Method
Randomized controlled trial
law
Internal medicine
polycyclic compounds
Humans
Medicine
Child
Alleles
Genetics (clinical)
Cross-Over Studies
business.industry
Cholesterol
nutritional and metabolic diseases
medicine.disease
Crossover study
Smith-Lemli-Opitz Syndrome
030104 developmental biology
chemistry
Smith–Lemli–Opitz syndrome
Child, Preschool
Physical therapy
Female
lipids (amino acids, peptides, and proteins)
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 10983600
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine
- Accession number :
- edsair.doi.dedup.....2521af9baf01dd4b9b141a36ad1e7d5e