Simvastatin for Inflammatory Diseases?

Danish scientists have found that the cholesterol medicine known as simvastatin directly affects the immune system. The researchers—from Aarhus University—hope that this opens up a new pathway for treating diseases such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.

“Simvastatin—and statins in general—are not designed to have this effect. 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, ” relates Thomas Vorup-Jensen, Ph.D., associate professor at the Department of Biomedicine at Aarhus University, in the July 7, 2016 news release.

As indicated in the news release, “The reason for the positive effect is that the pharmaceutical acts as a ‘plug’ in the proteins that retain the immune cells in the inflammation zones. With the plug in place, the immune cells can no longer contribute to the inflammation, which is therefore reduced, leaving the patient feeling better. In the case of diabetes, for example, it can help reduce the risk of patients developing complications.”

Vorup-Jensen told OTW, “CD18 integrins are important molecules in supporting the adhesion of leukocytes in zones of inflammation. Several important therapeutically treatment either directly or indirectly targets such adhesion to lower inflammation. Statins are known to lower inflammation in a way not linked with the ability to affect cholesterol levels. Based on the chemical properties of simvastatin, we wanted to explore new mechanisms for the anti-inflammatory properties of simvastatin.

“In the past, it was demonstrated that statins can block the function of CD18 integrins. However, the mechanisms involved these adhesion molecules in their inactive state. As a consequence of inflammation, CD18 integrins switch into their activated state. We have identified a mechanism whereby simvastatin can also block integrin in their activated state. This supports a role of simvastatin in treatment of inflammatory diseases, where the inflammatory conditions often are pre-existing to simvastatin treatment.”

As for the future, Vorup-Jensen commented to OTW, “Our structural insight on the mechanism of inhibition is useful to design more effective drugs targeting the same molecules as simvastatin.”