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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Combined treatment with chenodeoxycholic acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis.

We studied the effect of chenodeoxycholic acid (CDCA) and a competitive HMG-CoA reductase inhibitor, pravastatin, on clinical symptoms and sterol metabolism in a 36-year-old Japanese man with cerebrotendinous xanthomatosis (CTX). He had marked tendon xanthomas and mild dementia, with obvious electroencephalographic (EEG) abnormalities. He was treated for 2 years with CDCA alone (0.6 g/d) and then for a further year with the combination of pravastatin (10 mg/d) and CDCA (0.6 g/d). For the following year, he was given pravastatin alone, and then was returned to combined treatment again. The plasma cholestanol level before treatment was 3.12 mg/dL, which was 20 times above the control level. After CDCA alone, the plasma cholestanol was reduced to 1.96 mg/dL, and this was further reduced to 0.92 mg/dL by combination therapy with CDCA and pravastatin. However, after the discontinuation of CDCA, his cholestanol levels returned to the pretreatment levels despite the continuing of pravastatin treatment. When the combination therapy was restarted, his cholestanol level was once again markedly reduced. His clinical symptoms showed a close association with the plasma cholestanol level; the xanthomas regressed remarkably and the mental retardation improved in association with normalization of EEG findings during treatment with CDCA alone or in combination with pravastatin. However, during treatment with pravastatin alone, his tendon xanthomas enlarged again and slow waves reappeared on the EEG. Because inhibition of cholesterol synthesis by treatment with the HMG-CoA reductase inhibitor alone was not effective in causing a reduction of cholestanol, the increase in plasma cholestanol levels in CTX may not have been solely due to increased cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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