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Scientists identify gene responsible for statin-induced muscle pain
Date:11/27/2007

We learned that atrogin-1 is rapidly turned on in wasting muscle, explains Lecker, who is an investigator in the Division of Nephrology at BIDMC and Assistant Professor of Medicine at HMS. Muscle wasting occurs in a large number of disease states, including cancer, AIDS, and kidney disease and can also occur when muscles are underused due to injury or lack of exercise. In the absence of atrogin-1 activation, he adds, muscle atrophy is diminished.

Since this initial discovery, atrogin-1 has been found in every existing model of muscle wasting, prompting Lecker and Sukhatme to investigate whether cholesterol-lowering statins might also be turning on this gene.

We reasoned that since atrogin-1 plays a key role in the development of wasting in skeletal muscle, it might also mediate part of [patients] sensitivity to statins, the authors write.

They proceeded to conduct three separate experiments to test this hypothesis. They first examined the expression of the atrogin-1 gene in biopsies of 19 human quadricep muscles from five control patients, six patients with muscle pain who were not being treated with statins and eight patients with muscle pain/damage who were using statins. Their results showed that atrogin-1 expression was significantly higher among the statin users.

Next, the scientists studied statins effects on cultured muscle cells treated with various concentrations of lovastatin. Compared with control samples, the lovastatin-treated cells became progressively thinner and more damaged. But remarkably, say the authors, the cells lacking the atrogin-1 gene were resistant to statins deleterious effects.

Finally, the authors tested the drug in zebrafish. And, they showed that just as in mammalian muscle cell culture, lovastatin led to muscle damage, even at low concentrations; as the concentration was increased, so too was the damage. And, once again, they observed that fish lacking the atrogin-1 gene were resistant t
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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