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LIVER GUARD
Can cancer genes combat
cirrhotic livers? asks Biplab Das
A cirrhotic liver is trauma enough. Waiting for a donor replacement is trauma multiplied. But, thanks to new researches, patients of liver cirrhosis, a degenerative liver condition, can breathe a sigh of relief. The studies not only hold the promise of prolonging the lives of patients while they wait for a donor, but also eschew the need for a replacement.
According to a report published in Science, a research team led by Ronald De
Pinho, Dana Farber Cancer Institute, found that mice show a tendency of developing liver cirrhosis with the gradual loss of
telomeres, caplike structures that protect chromosome ends. The team was successful in reverting liver degeneration by employing gene therapy, which thwarted loss of
telomeres.
About five years ago, Japanese researchers first identified that cirrhotic liver had shorter telomeres than healthy ones. "The finding suggested that telomeres attrition might be a crucial trigger for end-stage cirrhosis," says De
Pinho. On the basis of this hunch, researchers removed the gene that codes
telomerase, the enzyme responsible for making telomeres, in mice. This disrupted the enzyme's action leading to shorter
telomeres. The team followed it up by inducing liver injuries to the mice to facilitate cirrhosis. They found that because of the shorter
telomeres, the mice livers could not compensate the cell degeneration.
At this juncture, the animals were injected with adenovirus, a DNA virus, carrying the missing telomerase gene. This procedure was successful in restoring normal liver
function in the ailing mice.
In another research, Philippe Leboulch, Massachusetts Institute of Technology, and Ira Fox, University of Nebraska, have developed a special type of liver cell called
NKNT-3 which divides relentlessly, providing metabolic aid to a manufacturing liver. In previous attempts, it had been found that cultured liver cells or hepatocytes failed to rev up cell division. The two collaborators of this experiment overcame the impediment by introducing a cancer gene called Large T
Antigen which brought about unbridled cell growth, reversing the cirrhotic condition.
However, Leboulch and Fox had to design them in such a manner that they could be removed before it began to threaten the host with cancerous growth. So far, both are happy with the success rate of their method. Of the animals injected with the cells, 60 per cent survived.
"This system might just do away with the shortage of hepatocytes that liver cirrhosis induces. You can keep the cells in the freezer and take them out whenever needed," points out Fox.
Till date, none of these therapies have been tried on humans, though the researchers are confident of their success. However, the latter research poses the question whether the NKNT-3 cells can be actually removed before they become carcinogenic. Achilles
Demitrion, a liver expert at the Cedars-Sinai Medical Centre, Los Angeles, suggests a safer therapy. He thinks that instead of introducing cancer genes, young stem cells could be coaxed to differentiate into liver cells, providing enough hepatocytes to prolong transplants.
Whatever the perfect remedy might be, it will be sometime before it can be of any help to patients of liver cirrhosis.
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