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Selective Thyromimetic Lowers LDL Cholesterol

Bile acid synthesis also stimulated, without cardiac side effects

FRIDAY, Dec. 28 (HealthDay News) -- Treatment with a synthetic, selective thyromimetic improves dyslipidemia without apparent cardiac side effects related to thyroid hormone, according to a report published online Dec. 26 in the Proceedings of the National Academy of Sciences Early Edition.

Anders Berkenstam, Ph.D., of the pharmaceutical company Karo Bio AB in Huddinge, Sweden, and colleagues administered the compound KB2115 to 48 people with moderately elevated total plasma cholesterol levels and body weights. In a single-dose study, four groups of five subjects each were randomized to receive single doses of KB2115 in 50, 200, 500 and 2,000 μg, and one subject in each group received placebo. In a multiple-dose study, KB2115 was administered to three groups of six subjects each in once-daily doses of 50, 100 and 200 μg for two weeks, and two subjects in each group received placebo.

During the two-week study, low-density lipoprotein (LDL) cholesterol levels were reduced up to 40 percent, compared to 11 percent in the placebo group. Similar effects of total cholesterol and apolipoprotein B levels were also observed. No significant changes were observed in high-density lipoprotein or triglyceride levels. Measurements of bio-markers showed an increase in bile acid synthesis in the absence of an effect on cholesterol synthesis.

"These findings in humans are an important step in evaluating thyromimetics as a strategy for treatment of dyslipidemia," the authors conclude.

In addition to the lead author, several co-authors of this study are employees of the pharmaceutical company Karo Bio AB. Another co-author is an employee of Berzelius Clinical Research Center AB.

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