Researchers at the University of British Columbia and University of Wisconsin-Madison have uncovered the molecular mechanism behind statin-induced muscle pain. Published in Nature Communications, the study used cryo-electron microscopy to show that atorvastatin holds open the RyR1 calcium channel in muscle cells through a three-molecule pocket binding process. This continuous calcium leak causes muscle injury among the 200 million global statin users, offering a detailed roadmap to design safer cholesterol-lowering drugs.
Statin-induced muscle damage mechanism
- ▪The study by University of British Columbia researchers focused on atorvastatin, finding that its molecular interactions with muscle proteins suggest similar effects occur across the statin family.
- ▪Researchers at the University of British Columbia and University of Wisconsin-Madison published a study in Nature Communications showing statins can trigger muscle pain and severe muscle breakdown leading to kidney failure.
Ryanodine receptor calcium leak
- ▪A study led by University of British Columbia researchers showed three statin molecules occupy a pocket in the RyR1 channel, with two holding the channel open to allow calcium leakage.
- ▪University of British Columbia researchers found that statins hold open the ryanodine receptor protein, known as RyR1, causing continuous calcium leakage that injures muscle cells.
Cryo-electron microscopy structural findings
- ▪Cryo-electron microscopy revealed atom-level details of how statin molecules latch onto and alter the ryanodine receptor calcium channel in muscle cells.
- ▪Researchers at the University of British Columbia used cryo-electron microscopy at their faculty of medicine facility to examine the atomic structure of the RyR1 muscle protein.
Safer statin development strategies
- ▪Drug developers can potentially eliminate statin-induced muscle pain by modifying specific features of statin molecules that interfere with the RyR1 protein while preserving cholesterol control.
- ▪Researchers at the University of British Columbia stated that structural insights into statin binding on RyR1 proteins provide a roadmap for designing modified statins that do not damage muscle tissue.
Statin side effect prevalence
- ▪More than 200 million people worldwide use statins to lower cholesterol and prevent heart attacks and strokes, according to a study published.
- ▪Widespread statin side effects such as muscle soreness, weakness, and fatigue cause some patients to discontinue their cardiovascular medication.
Story comments
Loading comments…