Now the physician Dr. Junfeng An of the Max Delbrück Center (MDC) Berlin-Buch and Dr. Stefan Donath, a specialist in cardiology (MDC and Helios Klinikum Berlin-Buch), have developed a new treatment approach based on a mouse model.
In their current study published in (Hepatology, doi:101002/hep.25697; Vol. 56, No. 2, August 2012)*, the liver failure was reversed and the mice recovered completely. The researchers hope to soon be able to test their new approach in clinical trials.
According to an estimate published in a 2011 issue of the “Deutsche Ärzteblatt”, a professional journal for German physicians, between 200 and 500 patients suffer from acute liver failure in Germany each year. Poisoning from mushrooms or drugs is one of the main causes of this serious liver disease. In Southern Europe, Africa and Asia an acute infection with the hepatitis B virus is considered to be the most important cause.
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 Dr. 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 Dr. 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,” Dr. 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.”
During their studies, the researchers also discovered a new active mechanism of ARC, which apparently is responsible for the protective function of this protein in the liver. It inhibits the activity of a molecule (JNK), which is activated in immune cells of the liver and causes abnormal processes, whereby another molecule (TNF alpha) is released that causes the liver cells to die. ARC thus protects the liver cells from destruction. The researchers hope to soon be able to test their new approach in clinical trials with patients.
Dr. Donath and the MDC have patented the fusion protein TAT-ARC for the indication of acute liver failure. The research project was funded by the MDC Pre-Go-Bio project, an internal project fund of the MDC that supports the transfer of diagnostic or therapeutic procedures obtained in basic research into clinical applications.*TAT-ARC protein transduction rescues mice from fulminant liver failure
Barbara Bachtler | Max-Delbrück-Centrum
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy