Lovastatin in ALD
New England Journal of Medicine 2010 Jan 21;362(3):276-277.
In 1999, it was reported that the cholesterol-lowering drug lovastatin reduced very long-chain fatty acids (VLCFA) in the blood of patients with X-linked adrenoleukodystrophy (Singh et al. 1998). As a result of this publication, many ALD patients worldwide began taking lovastatin in the hope that it would have a positive effect on clinical outcome. In the following years, other investigators questioned the beneficial effect of lovastatin on VLCFA. A subsequent study of simvastatin (a structurally related statin) in boys with cerebral ALD showed no effect on VLCFA (Verrips et al. 2000). And treatment of ALD mice had no effect on brain and adrenal VLCFA levels (Cartier et al. 2000, Yamada et al. 2000).
To determine whether lovastatin could truly reduce plasma VLCFA in patients with ALD, a randomized, double-blind, placebo-controlled, crossover study was conducted (Figure). Fourteen patients with the adrenomyeloneuropathy (AMN) phenotype were enrolled. Patients were treated with lovastatin for 6 months followed by 6 months of placebo or vice versa. Neither the patients nor the researchers knew who was taking which drug during the treatment period. At the end of the study, the samples and data were analyzed.
As expected, lovastatin treatment reduced plasma LDL cholesterol levels. Plasma VLCFA levels decreased by about 20%, but remained between 2 and 3 times higher than normal. In addition, VLCFA levels in red and white blood cells remained unchanged after lovastatin treatment. Because VLCFA are virtually insoluble in water, most VLCFA in the blood are transported as cholesterol esters in lipoprotein particles such as LDL. When these were analyzed, no effect on VLCFA levels in LDL particles was observed.
The authors conclude that lovastatin causes a small decrease in plasma VLCFA levels, which must be considered a non-specific consequence of the reduction in LDL cholesterol. Physicians should not prescribe lovastatin as a VLCFA-lowering therapy to patients with ALD, as there is no evidence to support this.Figure: Design of the randomized, double-blind, placebo-controlled, crossover study to evaluate the effect of lovastatin on VLCFA levels in plasma and blood cells of patients with ALD.
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