Simvastatin does not normalize very long chain fatty acids in adrenoleukodystrophy mice.
X-linked adrenoleukodystrophy (ALD) is a genetic demyelinating disorder characterized by accumulation of very long chain fatty acid (VLCFA) in tissues. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, normalizes VLCFA in fibroblasts and plasma from ALD patients. We dietary treated ALD mice with simvastatin, an analog of lovastatin with similar pharmacokinetics and effects on plasma VLCFA in ALD patients at 20 or 60 mg/kg/day for 6-12 weeks. No decrease of VLCFA content was observed in mouse tissues, including the brain. A significant increase of VLCFA was rather observed in the brain of ALD mice at 60 mg/kg/day.
Inserm U342, Hôpital Saint-Vincent de Paul, 82 avenue Denfert Rochereau, 75014, Paris, France. cartier@cochin.inserm.fr
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Cartier
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Guidoux
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Rocchiccioli
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P
Aubourg
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000326:Adrenoleukodystrophy / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D005227:Fatty Acids; D002784:Cholesterol; D019821:Simvastatin