MedWire News: The muscle pain and weakness experienced by some patients taking cholesterol-lowering drugs called statins may be caused by overactivation of a gene called atrogin-1, study results suggest.

"Although it is not known exactly how many of the 500 million individuals who take statins experience muscle pain and weakness, muscle symptoms are generally considered the most common side effects of these medications," explained lead researcher Dr Vikas Sukhatme, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, USA.

As previous research has shown that the atrogin-1 gene is overactive in a variety of conditions and diseases that cause muscle wasting, Dr Sukhatme and team conducted three separate experiments to investigate whether statins can trigger this gene and cause muscle weakness.

In the first experiment, the researchers studied muscle cells taken from five healthy people, six patients with muscle pain who were not being treated with statins and eight patients with muscle pain and weakness who were using these drugs. They found that atrogin-1 'expression' was significantly higher among the statin users than the other participants.

The team then studied the effects of statins on muscle cells with and without the atrogin-1 gene. The findings showed that cells with the atrogin-1 gene became progressively thinner and more damaged the longer they were exposed to statins, while those that lacked the gene remained largely unaffected.

In the final experiment, the researchers exposed zebrafish muscle cells to statins and found that, even at low concentrations, the drugs caused cell damage.

Commenting on the findings, co-researcher Dr Stewart Lecker, also from the Beth Israel Deaconess Medical Center, said: "These three complementary experiments demonstrate that atrogin-1 has a fundamental role in statin-induced toxicity."

He added: "Future experiments will be aimed at understanding how statins turn on the atrogin-1 response in muscle, and in ascertaining what transpires in muscle following atrogin-1 activation that leads to muscle damage and atrophy [wasting].

"The hope is that eventually patients will be able to glean statins' positive benefits to cholesterol metabolism and reduction of cardiovascular events while being spared accompanying muscle toxicities." The research will be published in a forthcoming issue of the Journal of Clinical Investigation.