July 12 (UPI) -- Researchers have discovered why scar tissues in some fibrotic diseases strangle vital organs, and may have identified the trigger and a method of treatment.
In a Northwestern Medicine study, researchers found the trigger of fibrosis in diseases that include diabetic kidney fibrosis, alcoholic liver cirrhosis, hepatitis C, pulmonary fibrosis and nonalcoholic fatty liver disease. The findings were published Thursday in the Journal of Clinical Investigation Insight.
"Our study opens a new door into fibrosis by looking at it as an aberrant innate immune response and suggesting a novel approach to treat it," senior author Dr. John Varga, director of the Northwestern Scleroderma Program and a distinguished professor of rheumatology at Northwestern University Feinberg School of Medicine, said in a press release. "In the U.S., many of these diseases are lifestyle or age dependent. As we get fatter or older, they get worse."
Fibrosis causes an estimated 35 percent to 40 percent of deaths in the world, according to a National Institutes of Health study. Nonalcoholic fatty liver disease may lead to fibrosis of the liver, which is the leading cause of liver transplant.
"There is an emerging direction for treating fibrosis with precision medicine," said Dr. Swati Bhattacharyya, scientific director of the Scleroderma Research Laboratory at Feinberg and first author of the study. "Some people live with fibrotic disease for 30 years while others die in two years. We need to identify the rapid progressors from the slow progressors."
Normally, scar tissue forms to heal an internal wound. Most fibrotic disease starts to repair an injury, "but if the immune system produces too much of an initial scar, it can't go back to normal," Varga said. "You have an unhealed scar that keeps growing and can wipe out the entire organ."
In one subset of human fibrosis cells, delinquent molecules continually worked against an immune receptor to produce scar tissue instead of allowing the scar tissue to go back to sleep.
The Northwestern scientists, working with University of Colorado researchers, used crystallography and computer modeling to find a molecule that could block the receptor and the uncontrolled scarring.
The abnormality was significantly reversed when they tested a molecule, T53, in three different mouse models of fibrosis.
Researchers hope that T53 is eventually developed into an approved drug for those patients with the specific genetic signature. They noted everyone's fibrosis is not caused by the same abnormality.
"The results of this study are encouraging," said Varga, who has spent more than a decade researching the cause and treatment of scleroderma, a type of fibrosis that affects multiple organs at one time. "We are not saying this compound is ready to be a drug. It's an initial compound that would need to be developed and tweaked. It would need significant funding to go to the next step."