Lovastatin and sodium phenylacetate normalize the levels of very long chain fatty acids in skin fibroblasts of X- adrenoleukodystrophy.
The present study underlines the importance of lovastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, and the sodium salt of phenylacetic acid (NaPA), an inhibitor of mevalonate pyrophosphate decarboxylase, in normalizing the pathognomonic accumulation of saturated very long chain fatty acids (VLCFA) in cultured skin fibroblasts of X-adrenoleukodystrophy (X-ALD) in which the ALD gene is either mutated or deleted. Lovastatin or NaPA alone or in combination stimulated the beta-oxidation of lignoceric acid (C24:0) and normalized the elevated levels of VLCFA in skin fibroblasts of X-ALD. Ability of lovastatin and NaPA to normalize the pathognomonic accumulation of VLCFA in skin fibroblasts of X-ALD may identify these drugs as possible therapeutics for X-ALD.
Singh
I
I
Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA. singhi@musc.edu
Pahan
K
K
Khan
M
M
D000326:Adrenoleukodystrophy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004357:Drug Synergism; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014960:X Chromosome / Q000235:genetics*
D005227:Fatty Acids; D010648:Phenylacetates; D008148:Lovastatin; C025136:phenylacetic acid; C010210:lignoceric acid; D008798:Mevalonic Acid