A multidisciplinary team of researchers led from Karolinska Institutet in Sweden have developed an anti-inflammatory drug molecule with a new mechanism of action.
By inhibiting a certain protein, the researchers were able to reduce the signals that trigger an inflammation.
“We’ve developed a new drug molecule that inhibits inflammation,” says Professor Thomas Helleday, at the Department of Oncology-Pathology, Karolinska Institutet, Sweden, who co-led the study with Dr Torkild Visnes and Dr Armando Cázares-Körner. “It acts on a protein that we believe is a general mechanism for how inflammation arises in cells.”
It was when developing a new molecule for inhibiting the enzyme that repairs oxygen damage to DNA that the researchers found, to their surprise, that it also dampened inflammation. It turned out that the enzyme OGG1, apart from repairing DNA, also triggers inflammation.
The inhibitor blocks the release of inflammatory proteins, such as TNF alpha. In trials on mice with acute pulmonary disease, the researchers succeeded in dampening the inflammation.
Could give rise to new treatments
“This discovery could give rise to a new treatment for a very serious condition,” says Professor Helleday. “We’ll now be developing our OGG1 inhibitor and examining whether it can lead to new treatments for inflammatory diseases in order to cure or relieve diseases such as sepsis, COPD and severe asthma.”
The repair pathway on which OGG1 operates was discovered by Tomas Lindahl at Karolinska Institutet in the 1970s, an achievement that earned him the Nobel Prize in Chemistry in 2015.
The study is published in Science and was done in collaboration with the University of Texas Medical Branch, Uppsala University and Stockholm University.
Some of the authors, including Thomas Helleday, are listed as inventors on a US patent application for OGG1 inhibitors. The patent is owned by the Helleday Foundation, of which Thomas Helleday and co-author and KI researcher Ulrika Warpman Berglund are board members and through which they are involved in the development of OGG1 inhibitors for clinical application.
Thomas Helleday, Professor at the Department of Oncology-Pathology, Karolinska Institutet, Sweden. Photo: Ulf Sirborn