Alcohol-related liver disease (ALD) is a fatal condition targeting more than 150 million people. Part of what makes it deadly is the unavailability of treatment besides a transplant. To address these challenges, researchers at Massachusetts General Hospital (MGH) have uncovered key molecular steps involved in ALD that may provide targets for drug therapy development.
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The groundbreaking findings were published in Proceedings of the National Academy of Sciences (PNAS) and describes how researchers achieved their results by combining RNA sequence analysis of patient liver samples with transgenic mouse studies. Researchers were able to identify two promising potential molecular targets for developing ALD therapeutics-- cGAS and Cx32. The senior author is Suraj J. Patel, MD, PhD, a research fellow in the Department of Medicine.
"Now that we know the key players in this pathway, we finally have drug targets for treatment development," says the lead author on the study is Jay Luther, MD, gastroenterologist and Director of the Mass General Alcohol Liver Center. "Until now, we haven't had any successful leads. Meanwhile, the number of patients has grown."
Before the study, scientists already knew that liver cell (hepatocyte) death in ALD is supported IFN regulatory factor (IRF3) which fuels a strong secondary inflammatory response that affects nearby cells eventually leading to liver failure. However, the question they came up with was how does alcohol activate IRF3 and which pathways are amplified that deliver the disease spread throughout the liver.
"Until now, now we had only few clues about why alcohol-related liver disease progresses the way it does, but this research fills in key pieces of the puzzle," says Patel.
"It is very encouraging to see that we now have evidence-based targets for drug development for ALD," says Luther.
Source: Science Daily