New inhibitor that blocks inflammation could also treat sepsis

Scientists at the University of Sheffield have discovered a new inhibitor that reduces lung inflammation and could be the key to treating acute respiratory distress syndrome, a life-threatening disease that affects thousands of people in the UK -United.

In this pioneering research, an international team of scientists aimed to manufacture an inhibitor of an enzyme involved in the repair of oxidized DNA, OGG1.

The study found that OGG1 protein signaled inflammation and that the newly created inhibitor could prevent the onset of inflammation. This is a new mechanism – different from other currently available anti-inflammatory drugs – that could also help prevent the attack of our immune system in conditions such as sepsis, multiple sclerosis, Crohn's disease and potentially other autoimmune disorders.

Inflammation is a process by which the white blood cells of the body protect us from infections, such as bacteria and viruses. However, under certain conditions, the immune system triggers an inflammatory reaction when there is no infection to fight. This has the effect that the body's normally protective immune system damages its own tissues.

Professor Thomas Helleday, of the Department of Oncology and Metabolism at the University of Sheffield and lead author of the study, said: "When the regulation of oxygen in our cells becomes deteriorate, it can damage our DNA and provoke the response of our immune system.

"Our immune system is our defense mechanism that normally fights invasions of bacteria and viruses, but it can sometimes cause misfires and attack our own body.

"Isolating an inhibitor that may disable this response is a major breakthrough and we are very excited to continue our research to see if we can not only reduce the existing inflammation in other regions of the world. body, but also prevent it.

"This would pave the way for new and effective treatments for diseases such as life-threatening sepsis."

The study, which lasted six years, was conducted in collaboration with scientists from around the world, including the Karolinska Institutet, the Medical Branch of the University of Texas at Galveston and the University. from Stockholm.

The results are published on November 15 in the journal Science.

"In contrast to other studies, we wanted to examine the occurrence of inflammation associated with DNA damage caused by poor regulation of oxygen," said the Professor Helleday.

"We found proof of concept that oxidative DNA repair is targeted to relieve inflammatory conditions.

"We now hope to further develop the research and conduct the study at clinical trials."

Helleday, a former member of the Karolina Institutet in Sweden, previously discovered how PARP inhibitors (poly-ADP ribose polymerase) can be used as a tailor-made treatment for patients with BRCA2 mutations, seen in both hereditary cancers of the ovary and breast. The discovery, made at the University of Sheffield, has since saved thousands of lives and the drug Lynparza has become the first treatment to be approved for cancer patients carrying the BRCA gene mutation.

Source: University of Sheffield