Millions of people rely on statins, drugs used to lower cholesterol and reduce the risk of heart attack and stroke. However, for some people, this drug comes with undesirable trade-offs, such as muscle pain, weakness, and exercise intolerance, which can make it difficult to continue treatment.
Now, researchers at McMaster University have discovered a biological pathway that may explain why these side effects occur, opening the door to future treatments that may make statins easier to tolerate while preserving their life-saving cardiovascular benefits.
Published in scientific progressthis study identifies the immune and metabolic mechanisms that cause statin-induced muscle damage and questions long-held assumptions about how these side effects occur.
Statins are among the most effective drugs we have for reducing the risk of cardiovascular disease and preventing premature death. ”
Jonathan Scherzer, professor in the McMaster School of Biochemistry and Biomedical Sciences and senior author of this study
“Unfortunately, muscle side effects can cause some people to reduce their drug dose or stop taking the drug altogether. We wanted to know why this happens and whether we can distinguish side effects from benefits.”
Muscle symptoms associated with statins affect an estimated 7 to 29 percent of people taking the drugs. Researchers have long known that statins can sometimes cause muscle problems, but the biological mechanisms behind their effects remained unclear.
A research team led by lead authors Nazri Robin and Nicole Barra from McMaster’s Scherzer lab found that statins can interfere with how muscle cells produce energy and trigger an immune response that damages muscle tissue. In experiments using muscle cells and mouse models, the researchers were able to prevent much of that damage by blocking the immune response.
“One of the most interesting findings in the study is that the mechanism that causes muscle side effects appears to be separate from the mechanism that lowers cholesterol,” Scherzer said. “This suggests that it may one day be possible to target side effects without interfering with the cardiovascular benefits that make statins so valuable.”
The study also revealed an unexpected link between metabolism and immunity. Researchers have discovered that changes in muscle cell metabolism trigger an immune response within the cells themselves, providing new insight into how inflammation contributes to drug side effects.
Although additional research is needed before the findings can be translated into patient treatment, the findings identify several potential targets for future drug development aimed at preventing statin intolerance.
“These findings provide a clearer understanding of why some patients experience muscle symptoms and provide promising directions for making these important drugs safer and more effective in the future,” Scherzer added.
The study reflects extensive international collaboration, including researchers from the Center for International Infectious Disease Research (CIRI) in Lyon, France. Muscle Research Center, University of Melbourne, Australia. Murdoch Children’s Research Institute and Royal Children’s Hospital, Australia; York University, Canada. and McMaster Department of Pathology and Molecular Medicine.
This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC).
