A new study reveals how cholesterol-lowering drugs can trigger muscle damage — and points to a way to make them safer.
As statins transformed cardiovascular health, saving millions of lives reduce cholesterol and reduce the risk of myocardial infarction and stroke.
But for many patients, these medications have a worrying side effect: muscle pain, weakness and, in rare cases, severe muscle degradation that can lead tokidney failure.
In a new study, researchers at the University of British Columbia (UBC) and their collaborators at the University of Wisconsin-Madison have now identified the cause of these effects.
Their conclusions, presented in a recently published in the journal Nature Communicationscan pave the way for a new generation of statins without these side effects.
The team used cryo-electron microscopyan advanced imaging technique that reveals proteins in near-atomic detail, to capture how statins interact with a critical muscle protein called the ryanodine receptor (RyR1).
This protein works as a gate for calcium inside the muscle cells, opening only when the muscles need to contract.
When statins bind to it, they force the gate open, causing a continuous calcium leak — a toxic effect that can damage muscle tissue.
“We were able to see, almost atom by atom, how statins attach to this channel,” he explains. Steven Molinarolo, researcher in the department of biochemistry and molecular biology at UBC and the lead author of the study, at the university.
“This calcium leak explains why some patients suffer from muscle pain or, in extreme cases, potentially fatal complications“, adds
The study focused on atorvastatin, one of the most prescribed statins, but the findings suggest that the effect may be common to the entire class of medicines.
Researchers have found that statins bind in a highly unusual way: three molecules group together inside a protein cavity. The first molecule binds when the channel is closed, preparing it to open. Two additional molecules fit later, forcing the channel to open completely.
“This is the first time we have a clear picture of how statins activate this channel”, says Filip Van Petegem, senior author and professor at the UBC Life Sciences Institute. “It is a great advance because it gives us a roadmap for design statins that do not interact with muscle tissue“.
By tweaking just the parts of the statin molecule responsible for negative effects, scientists can preserve the part that lowers cholesterolsimultaneously reducing risk.
Although serious muscle injuries only affect a small fraction of more than 200 million statin users Around the world, milder symptoms such as pain and fatigue are much more common and often lead patients to discontinue treatment.
The new discoveries could help prevent these problems and improve adherence to a life-saving therapy.
“Statins have been a mainstay of cardiovascular care for decades,” says Van Petegem. “Our goal is make them even saferso that patients can benefit without fear of serious side effects.”
For millions of people who rely on statins, this could mean fewer muscle problems — and a better quality of life.
