Small molecule restores liver regeneration

Paracetamol overdose is the most common cause of Acute Liver Failure, with around 200 UK and 2,000 US life threatening cases each year. Researchers have now find a way to prevent liver failure caused by toxic drugs by supporting the liver’s natural ability to regenerate.

In a study in mice by researchers at the University of Edinburgh MRC Centre for Regenerative Medicine and the Cancer Research UK Beatson Institute in Glasgow together with Spanish and Belgian co-workers,  found liver injury, triggers a process – called cellular senescence – usually associated with aging or chronic disease. Cellular senescence occurs when injured cells permanently stop growing. Liver samples from patients with acute liver injury showed impaired liver regeneration and the expression of several biological markers associated with senescence, and mice with Paracetamol poisoning also displayed senescent liver cells.

Notably, two other mouse models showed that senescence could spread from injured liver cells to uninjured cells through the signaling molecule TGF-?. Administering a small-molecule inhibitor of TGF-? to mice 12 hours after Paracetamol poisoning reduced liver injury and increased regeneration, showing that the molecule could be a workable therapeutic target for future research efforts.

"We have identified a potential treatment for acute liver failure, which may prevent the need for transplant," said Bird. "While transplant offers incredible life-saving opportunities for these patients, it does mean a major operation and a lifetime of medication. New treatments like TGF-? inhibitors, which set liver regeneration free and may prevent the need for liver transplants, would make a huge difference for these patients."