New Approach to Treat Acute Failure

Photo: Liver targeting

Poisoning from mushrooms or
drugs is one of the main causes of
liver failure;© panthermedia.net/
Sebastian Kaulitzki

Acute liver failure is a life-threatening disease. Unfortunately, few treatment options exist, especially for advanced-stage liver failure. As a last resort a liver transplant may be the only remaining option.

For their treatment approach the two researchers utilized the recently discovered protein ARC (apoptosis repressor with caspase recruitment domain), which serves as the body’s own survival switch. ARC is expressed in heart and skeletal muscle and in the brain, but not in the liver. In 2006 Doctor Stefan Donath showed that apoptosis is the cause for the death of myocardial cells during heart failure, but that ARC stopped the myocardial cells from being destroyed.

Apoptosis protects the body from diseased or defective cells. In tumor cells apoptosis is deactivated, allowing the cancer cells to proliferate uncontrollably. Cancer researchers are therefore striving to utilize apoptosis to develop a treatment. They are looking for ways to reactivate apoptosis to drive the proliferating cancer cells into programmed suicide. However, in acute liver failure the problem is not too little but rather too much apoptosis. Physicians administer drugs in an attempt to halt the destruction of the cells, but only with modest success.

Now Donath and his colleagues 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. 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 said. “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. In addition, 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.”

MEDICA.de; Quelle: Max Delbrück Center (MDC) Berlin