The liver is famous for its ability to regenerate itself, able to fully regrow even after two-thirds of its mass has been surgically removed.
However, in the case of severe liver damage caused by drugs, alcohol abuse or obesity, liver failure may occur. If in the terminal stage, liver failure today can only be treated with a transplant.
And with the shortage of organs available for transplantation, this is a very serious problem. The average wait for a liver transplant 5 months, it often leaves victims in its path.
What would happen if instead of a transplant there was a drug that helps the liver to regenerate even in these cases?
On the hunt for a “liver saver”
Satdarshan Monga, Professor of Pathology and Medicine at the University of Pittsburgh, directs a laboratory that studies liver regeneration.
Recently, during clinical trials with overweight mice, he discovered that the activation of a particular protein with a new drug accelerates liver regeneration and repair even after severe liver injury. I link the tests here.
It is news that can bring very good things to such an important organ. Let's talk about an organ that plays more than 500 key functions in the body (including carrying fat or converting excess glucose into glycogen for the breakdown of toxins).
Liver cells, or hepatocytes, perform these numerous functions with a strategy called zoning. In short: the liver is divided into three zones with different tasks, and cells are directed to perform specialized functions by activating specific genes in each zone. However, what exactly controls the expression of these genes has been poorly understood.
The key: Wnt proteins
Over the past two decades, Monga's team and other labs have identified a group of 19 proteins called Wnt which play an important role in the control of liver function and regeneration (as well as in the growth of embryonic stem cells).
However, which of these proteins actually control zoning and regeneration, as well as their exact location in the liver, were a mystery.
To solve it, the team headed by Satdarshan Monga used a new technology called molecular cartography and identified where as many as 100 genes that regulate liver function are active.
And what did he discover?
Only two of the 19 Wnt genes, Wnt2 and Wnt9b, were functionally present in the liver. Wnt2 and Wnt9b were found in endothelial cells lining blood vessels in zone 3 of the liver, an area that plays a role in several metabolic functions.
Removal of these two Wnt genes resulted in liver cells expressing only genes typical of zone 1, significantly limiting overall liver function. Regeneration also stopped.
This suggests that liver cells experience continuous activation of genes that could modify their functions, and Wnt is the master regulator of this process.
Tests for the drug that helps the liver repair itself
After the first tests looking for solutions, the team tested a new one drug to help recover liver zoning and regeneration. This drug, an antibody called FL6.13, shares similar functions with Wnt proteins, including triggering liver regeneration.
Over the two days of the study, the researchers administered this drug to the mice, and found that the drug was able to almost completely recover liver cell division and repair functions.
Ultimately, in efficacy tests, the drug was “deployed” against paracetamol intoxication, one of the most common causes of serious liver damage requiring a transplant. And it reduced biomarkers of liver damage in the blood and liver tissue death.
Reduce transplants to zero?
The shortage of organs to be transplanted can be reduced or eliminated if we intervene directly on liver diseases.
Investments in pharmacological medicine are needed, but the path is the right one.
