Dr. Paul Monga, director of Pittsburgh’s Liver Research Center, and his team are studying cancer and liver regeneration. Dr. Monga recently published a study that finds activation of a medication with a specific protein aids in facilitating the repair and regeneration of the liver in mice. This was accomplished after severe injury to the liver and even after partial removal of the liver.
According to a recent article in The Conversation, over five hundred functions are carried out by the liver. Although the liver regenerates itself, there is a limit to the number of livers available for transplantation.
The waiting time in the United States for a liver transplant may be anywhere from thirty days to five years. For instance, in 2021 only 9,200 patients received a transplant out of a waiting list of 11,600 patients. There are not many effective treatments available for liver illnesses. Therefore, if the disease worsens patients will require liver transplants.
Dr. Monga told The Conversation that a group (Wnts) of nineteen proteins have been observed that play key roles in regulating regeneration and liver function. Although researchers have long since been aware that Wnt proteins activate the process of repairing liver cells that have been damaged, they have been unable to determine which proteins regulate regeneration and zonation or to identify their location within the liver.
The doctor explained that in order to identify the proteins he and his team relied on molecular cartography that tracks the activity of one hundred genes. The search resulted in locating two Wnt genes Wnt2 and Wnt9b.
The researchers discovered that after eliminating the two genes the liver’s function became significantly limited. This process explained Wnt’s role as a ‘master regulator’.
Dr. Monga also discovered that when the Wnt genes were eliminated from the endothelial cells, liver cells no longer divided. This put a halt to liver regeneration and prompted the researchers to test an antibody called FL6.13.
Tylenol Overdose and Liver Regeneration
The researchers investigated FL6.13 in an effort to recover regeneration and zonation of the liver. The drug has functions similar to Wnt proteins such as liver regeneration.
Mice, genetically engineered without Wnt2 and Wnt9b, were given FL6.13 for two days. The drug successfully recovered almost all of the liver’s repair functions and cell division in the liver.
The OTC drug Tylenol (acetaminophen) is recommended for the treatment of pain and fever. In the U.S., an overdose of this medication is a common cause of liver transplantation. Other than transplantation there is only one drug that treats Tylenol overdose, but it must be taken almost immediately after the incident occurs.
The researchers tested FL6.13 on mice that were given doses of Tylenol that were toxic. With just one dose of the new drug, the death of liver tissue was reduced.
Dr. Monga suggested that the shortages in liver transplants may be eased by the creation of new drugs to treat liver diseases. Medications exist that can cure hepatitis C but this process does not apply to other liver diseases.
The doctor and his team believe that additional studies to improve liver regeneration will decrease the demand for liver transplants throughout the world.
