The purpose of this pilot study is to demonstrate the safety and efficacy of lovastatin in lowering the elevated levels of very long chain fatty acids (VLCFA) in patients with X-linked recessive adrenoleukodystrophy (XALD). Our preliminary studies in vitro show that lovastatin normalizes the VLCFA levels and increases the oxidation of lignoceric acid in cultured primary skin fibroblasts derived from XALD patients in about 15 days of treatment. In addition, in vitro studies with primary rat astrocytes, microglia and C6 cells, show that lovastatin suppresses cytokine induction and the induction of inducible nitric oxide synthase (iNOS). Since lovastatin crosses the blood-brain barrier, it may have beneficial effects on the brain, the target organ of inflammatory damage in XALD. Thus, lovastatin (and several other compounds that are effective in vitro) has the potential to be a landmark new development in the treatment of this devastating neurodegenerative disorder. The demonstration of the safety and efficacy of lovastatin in lowering accumulated VLCFA in vivo as proposed in this pilot study of XALD patients will pave the way for a larger Phase III clinical trial. The finding of efficacy in this pilot study is necessary prior to proposing an elaborate study of large enough numbers of patients over a period of time sufficient to show clinical benefits. Such a study will require 3 to 5 years of effort for which funding will be sought from a variety of extramural sources.
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