Workings of Common Statin, Simvastatin, Explored in Ways Relevant to Multiple Sclerosis

One of the world’s most commonly used medications — the cholesterol-lowering drug simvastatin — was found to affect the immune system in a way that can be explored to treat inflammatory diseases such as multiple sclerosis (MS).

Researchers have earlier noted that simvastatin, a cholesterol-lowering drug, is beneficial for MS patients. In a large study of people with secondary progressive MS, a disease stage many physicians do not treat, they showed that the drug reduced the rate of brain degeneration.

Simvastatin has shown an ability to halt immune-related disease processes, such as those in type 1 diabetes, MS, and rheumatoid arthritis. Exactly how the drug — developed with no such actions in mind — alters the workings of the immune system has, however, eluded scientists.

Analyzing the drug’s interactions with cells cultured in lab dishes allowed researchers at Aarhus University in Denmark to get a closer look at its activities.

The study, “Structural basis for simvastatin competitive antagonism of complement receptor 3,“ published in the Journal of Biological Chemistry, showed that the simvastatin molecule binds to an immune structure known as complement receptor (CR)3, preventing another factor from binding. When the natural factor can no longer bind, immune cells have no way to trigger immune processes, much as a person can’t charge a cellphone if an electrical socket is already occupied by another plug.

Complement factors are part of our first-line immunity helping other immune cells to launch an attack if they discover a threat. They are also involved in later stages of immunological processes. Since complement factors are involved in autoimmune disease, scientists have tried to develop drugs blocking their activity.

Thomas Vorup-Jensen, a professor in the Department of Biomedicine at Aarhus, believes these findings are particularly interesting because simvastatin does not produce the severe side effects other MS medications often cause.

“We have now identified a new mechanism that forms the basis for the effect, and this opens up new opportunities for developing a better substance to combat these inflammatory diseases. It’s an interesting line to pursue because a great many people can take statins without significant side effects,” Dr. Vorup-Jensen said in a news release.

Since the discovery was made in cells, the research team now hopes to prove the same is true in living organisms.

“Of course, we now need to establish whether it works in the same way in vivo, but we think it’s likely,” Dr. Vorup-Jensen said.

Earlier studies have also found that simvastatin prevents the release of immune cytokines, affecting the actions of immune T-cells, suggesting that the drug might affect the immune system in various ways.