Scientists at the University of British Columbia, working with colleagues at the University of Wisconsin-Madison, have uncovered a molecular mechanism behind statin-related muscle pain. Using cryo-electron microscopy, they observed how statins interact with the ryanodine receptor (RyR1), a protein that normally controls calcium release during muscle contraction. The study, published in Nature Communications, shows that statin molecules can latch onto this channel and hold it open, allowing calcium to leak continuously into areas where it should be tightly regulated.
The researchers focused on atorvastatin and found an unusual binding pattern: three statin molecules occupy a pocket in the protein. The first binds while the channel is closed and makes it more likely to open; two additional molecules then enter and keep it open. This continuous calcium leak helps explain why some patients experience soreness, weakness, or, in rare cases, severe muscle breakdown that can lead to kidney failure.
More than 200 million people worldwide use statins, and muscle-related side effects can lead some to stop taking the medication, losing protection against heart attacks and strokes. The structural details provide a roadmap for modifying statin molecules to avoid interacting with RyR1, potentially yielding safer cholesterol-lowering drugs. The authors caution that further research and drug development are needed before these findings translate into new treatments, but they offer a promising direction for reducing a longstanding safety concern.