Lovastatin in ALD

April 14th, 2016 |

Marc Engelen, M.D., Ph.D. & Stephan Kemp, Ph.D.

New England Journal of Medicine 2010 Jan 21;362(3):276-277.

New England Journal of Medicine that the cholesterol reducing agent lovastatin reduced very long-chain fatty acids (VLCFA) in blood from patients with X-linked adrenoleukodystrophy (Singh et al. 1998). As a result of the publication many ALD patients worldwide started using lovastatin with the hope that it will have a positive effect on the clinical outcome. In the following years, other researchers raised doubt on the beneficial effect of lovastatin on VLCFA. A subsequent study with 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 VLCFA levels in brain and adrenal (Cartier et al. 2000, Yamada et al. 2000).

To resolve whether lovastatin could truly reduce plasma VLCFA in patients with ALD, a randomized double-blind placebo controlled cross-over trial was carried out (Figure). Fourteen patients with the adrenomyeloneuropathy (AMN) phenotype participated in the trial. Patients were treated with lovastatin for 6 months and 6 months with a placebo, or vice versa. Neither the patients nor the researchers knew who was using what kind of medication during the treatment period. At the end of the trial the samples and data were analyzed.

As expected, treatment with lovastatin reduced plasma LDL cholesterol levels. The plasma VLCFA levels reduced by about 20%, but they remained between 2 and 3 times above the normal level. In addition, VLCFA levels in red and white blood cells remained unchanged after lovastatin treatment. Since VLCFA are virtually water insoluble, most of the VLCFA in blood are transported as cholesterol-esters in lipoprotein particles like LDL. . When these were analyzed, no effect on VLCFA levels was observed in LDL particles.

The authors conclude that lovastatin leads to a small decrease in VLCFA levels in plasma, which has to be considered a non-specific result of the decrease in LDL-cholesterol. Physicians should not prescribe lovastatin as a VLCFA lowering therapy to patients with ALD, since evidence does not support it.

Lovastatin Trial Design

Figure: Design of the randomized, double-blind, placebo-controlled, crossover trial to test the effect of lovastatin on VLCFA levels in plasma and blood cells of ALD patients.

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