Researchers find that blocking a specific DNA repair protein stops inflammatory response
GALVESTON, Texas – Inflammation is typically the body’s way of dealing with infections or irritants and starting the healing process. But like anything else, too much of a good thing can be harmful.
Chronic inflammation is associated with numerous diseases including different types of cancer, arthritis, Alzheimer’s and even aging.
Current drugs are only able to suppress inflammation but researchers at The University of Texas Medical Branch at Galveston, in collaboration with scientists at the Karolinska Institute in Sweden, believe they may have found a way to stop inflammation before it begins. The research team published their findings in Science.
Researchers, under the direction of Dr. Thomas Helleday, professor in the Department of Oncology and Pathology at the Karolinska Institute, developed a small molecule that binds to a key DNA-repair enzyme. Blocking that specific enzyme not only prevents, but ameliorates, the body’s inflammatory response, said Istvan Boldogh, professor at Department of Microbiology and Immunology at UTMB, and senior author of the paper.
The findings could lead to better treatment or prevention of a range of diseases including chronic obstructive pulmonary diseases, asthma, obesity, chronic arthritis, cardiovascular diseases, Alzheimer’s and others, according to the researchers.
Boldogh and his colleagues found that the initiation and exacerbation of the inflammatory processes are associated with damage to the body’s DNA. It is when the DNA-repair enzyme called 8-oxoguanine DNA glycosylase1, or OGG1, responds to the damage that the expression of inflammatory genes begin.
“This observation goes against the conventional dogma about the role of DNA repair protein OGG1,” said Boldogh.
A team of researchers in Sweden were able to develop small molecule inhibitors that fit into the active pocket of the repair enzyme OGG1, preventing it from binding to the damaged DNA and starting the gene expression needed for inflammation. In collaboration with Boldogh’s lab, they showed that the drug, called TH5487, could also decrease ongoing inflammation, a crucial finding for the treatment of chronic inflammation.
“Only a handful of times over their entire scientific career, one has the opportunity to be a part of a team to make a historic leap,” Helleday said. “This is just what we are experiencing right now.”
The small molecule has been tested successfully in mice. The next step is to begin clinical trials, which is what the research team is doing now, Boldogh said.
“We believe that controlling inflammatory diseases could also extend human lifespan, a remarkable achievement,” Boldogh said. “Possibilities like that make us believe that this discovery is going to be very significant.”