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'ARC' proteins could reverse acute liver failure: study

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In a new study by German researchers, the liver failure was reversed and the mice recovered completely and they hope to soon be able to test this approach in clinical trials with patients.

The researchers utilised the recently discovered protein ARC (apoptosis repressor with caspase recruitment domain), which serves as the body's own survival switch. ARC is present in heart, skeletal muscle and the brain, but not in the liver.

In cancer cases, apoptosis is deactivated in the tumour cells allowing the cancer cells to grow. Researchers are looking for ways to reactivate apoptosis to drive the proliferating cancer cells to die out.

However, in acute liver failure the problem is not too little but rather too much apoptosis.

The researchers have fused ARC to a noninfectious fragment of the human immunodeficiency virus(HIV), called TAT for short. The researchers used TAT as a shuttle to transfer this survival-switch construct into the liver.

"ARC is very fast acting, and this is a huge advantage, because in an emergency there is not much time for treatment. And when the massive damage is over, the liver is quite capable of regenerating itself," researcher and specialist in internal medicine and cardiology at Helios Klinikum Berlin-Buchsaid Dr Stefan Donath said in a press release.

Mice with acute liver failure were given an intravenous or intraperitoneal injection with the construct.

"Within just a few minutes the fusion protein TAT-ARC reached the liver of the animals and immediately began to take effect. ARC was able to stop the apoptosis of the liver cells, and all of the animals completely recovered," Donath added.

ARC reaches other organs via the bloodstream, not only the liver. "Moreover," he pointed out, "since TAT-ARC only has to be administered for a short time, a cancer risk can be largely excluded."

During their study, the researchers also discovered a new active mechanism of ARC, which apparently is responsible for the protective function of this protein in the liver.

Acute liver failure is a life-threatening disease, characterised by a sudden, massive death of liver cells. About 200 and 500 patients suffer from acute liver failure in Germany each year.

  

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