Scientists finally uncover why statins can cause muscle pain
Scientists have uncovered a surprising reason why statins, the widely prescribed cholesterol-lowering drugs that help prevent heart attacks and strokes, can sometimes cause muscle pain, weakness, and even severe muscle damage. Using advanced imaging technology, researchers discovered that statins can attach to a crucial protein in muscle cells and force open a channel that normally controls calcium flow. This causes…
Key points
- UBC and Wisconsin-Madison researchers found statins can hold open a muscle calcium channel called RyR1.
- Three statin molecules bind together in one pocket, with the first making the channel more likely to open.
- The findings, published in Nature Communications, could help design statins that spare muscle tissue.
Scientists at the University of British Columbia, working with colleagues at the University of Wisconsin-Madison, have identified a molecular mechanism that may explain why statins cause muscle pain and weakness in some patients. The findings were published in Nature Communications.
Using cryo-electron microscopy, the researchers examined the ryanodine receptor (RyR1), a protein that controls calcium movement in muscle cells. They found that statins can hold the channel open, letting calcium leak continuously into areas where it should be tightly regulated, which can injure muscle tissue.
How three molecules bind
The team focused on atorvastatin, a commonly prescribed cholesterol drug, though the results suggest similar interactions could occur with other statins. Three statin molecules occupy a single pocket in the protein: the first binds while the channel is closed and makes it more likely to open, and two more then hold it open.
Lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC's department of biochemistry and molecular biology, said the team could see "almost atom by atom" how statins attach to the channel, and that the calcium leak explains the muscle pain some patients experience.
That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications.
— Dr. Steven Molinarolo
What it could mean for patients
More than 200 million people worldwide use statins. Serious muscle breakdown is rare, but soreness, weakness and fatigue are more widespread and can lead some people to stop taking their medication.
Senior author Dr. Filip Van Petegem, a professor at UBC's Life Sciences Institute, said the work gives researchers a roadmap for designing statins that do not interact with muscle tissue. He said the goal is to make statins even safer so patients can benefit without fear of serious side effects. Further research and drug development are needed before new treatments result.
