Scientists from Canada and the US have solved a 30-year medical mystery, explaining why popular cholesterol-lowering drugs cause muscle pain. Research published in Nature Communications showed that statin molecules inadvertently attack muscle cells, triggering an uncontrolled release of calcium within them.
Scale of the Problem
Statins remain the “gold standard” in preventing cardiovascular disease. However, therapy is often complicated by serious discomfort. According to ScienceDaily, 10% to 25% of patients experience muscle pain, weakness, or cramps. This side effect is the main reason people voluntarily stop taking life-saving medications, significantly increasing the risk of heart attacks and strokes.
Off-Target: Scientific Discovery
For a long time, side effects were thought to be linked to general metabolic processes. However, new research has revealed a specific “molecular malfunction.”
A team led by Professor Filip Van Petegem (University of British Columbia) and Professor Lara Banks (University of Wisconsin–Madison) used cryo-electron microscopy to image molecular interactions with atomic precision. It turned out that statins affect not only liver enzymes but also mistakenly bind to RyR1 (ryanodine receptor)—a key protein channel in skeletal muscles.
“This is the first time we have gotten a clear picture of precisely how statins interact with this receptor. We saw that the drug literally hacks the gate that should be closed.”
— Data from EurekAlert release
How the Cell “Hack” Happens
In the study, results of which are published in the journal Nature Communications, scientists detailed the chronology of the damage. The process resembles forcing a door open and occurs in several stages:
- Priming: The first statin molecule attaches to the closed RyR1 receptor in a specific “pocket,” changing its configuration.
- Forced Opening: Then, two more statin molecules wedge into the protein structure. Acting as struts, they force the calcium channel to get stuck in the open position.
- Result: A constant “toxic leak” of calcium ions from intracellular stores occurs. This damages muscle fibers and triggers cell death signals, which patients perceive as pain and weakness.
Outlook: Next-Generation Drugs
Discovering the exact structure of the “statin-receptor” complex gives pharmacists a map for modifying drugs. Researchers believe it is possible to change the chemical formula of statins so they no longer “fit” into the pocket of the muscle RyR1 receptor but retain their effectiveness for the liver.
This opens a real path to creating a new class of drugs that will allow millions of people to control cholesterol levels without pain or risk to their muscles.
