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 inhibito r of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, and t he sodium salt of phenylacetic acid (NaPA), an inhibitor of mevalonate pyrophosphate decarboxylase, in normalizing the pathognomonic accumul ation of saturated very long chain fatty acids (VLCFA) in cultured ski n fibroblasts of X-adrenoleukodystrophy (X-ALD) in which the ALD gene is either mutated or deleted. Lovastatin or NaPA alone or in combinati on stimulated the beta-oxidation of lignoceric acid (C-24:0) and norma lized the elevated levels of VLCFA in skin fibroblasts of X-ALD. Abili ty of lovastatin and NaPA to normalize the pathognomonic accumulation of VLCFA in skin fibroblasts of X-ALD may identify these drugs as poss ible therapeutics for X-ALD. (C) 1998 Federation of European Biochemic al Societies.