Researchers in Göttingen, Germany, have identified a cancer drug as a prototype drug that may be used to treat Alzheimer’s disease. This substance, known as “Vorinostat”, was found to alleviate learning and memory problems in mice.
The scientists were also able to clarify how the substance acts upon the metabolism of nerve cells. A team led by Prof. André Fischer, who is a researcher at the German Center for Neurodegenerative Diseases (DZNE) and the University Medical Center Göttingen (UMG), reports these findings in the “Journal of Clinical Investigation”. The scientists now intend to test whether this or similar drugs may slow down the cognitive decline of people with dementia.
Alzheimer’s disease interferes with the organism’s normal functioning in many ways. One aspect that is increasingly becoming the focus of research is gene expression. This term is used to describe the phenomenon that only part of the DNA in a cell is active at any time.
“Some genes are switched on and others are switched off depending on the cell type and circumstance,” explains Fischer, site speaker for the DZNE in Göttingen and professor at the UMG. “In Alzheimer’s, this pattern of activity is dysregulated, particularly in the nerve cells inside the brain. This impairs learning skills and memory.”
Influencing gene activity
Certain gene expression regulators, called “histone deacetylase inhibitors”, have been under consideration for some time as a possible treatment for Alzheimer’s disease. Vorinostat - also known as SAHA and currently used to treat lymphoma - is one of the substances in this category.
“These drugs act upon helper proteins that are involved in gene expression. This can have a positive effect on medical conditions,” says Fischer. Such an impact was suggested by previous laboratory studies. However, as the researcher explains, until now there were not enough data to test these substances on patients.
Study of mice
“For this reason we made a detailed study. We looked how Vorinostat acts upon signs of aging, and also how it affects signs of disease. Our intention was to provide a basis for innovative clinical studies” says the neuroscientist.”
The researchers treated two groups of mice with learning and memory-related difficulties. In one group, the cognitive problems were age-related. The mice in the second group were younger, but harboured a genetic defect that leads to accumulation of protein aggregates such as those found in Alzheimer’s patients. These animals also showed distinct cognitive impairments.
“Vorinostat improved the learning and memory skills in both groups“, says Fischer. “We also found that it acts primarily on neurons. The drug alleviated brain inflammation and restored gene expression to an almost normal pattern.”
Furthermore, the study showed how Vorinostat promotes the ability of nerve cells to link up with each other. This ability is called “synaptic plasticity”. “Synaptic plasticity is essential for cognition”, Fischer explains. “Synaptic plasticity allows the brain to build connections among neurons and to rearrange them when needed. This is a prerequisite in order to process information efficiently.”
Next step: study with patients
“Ultimately, we were able to show what Vorinostat actually does - not only how it influences symptoms, but also what happens at the cellular level,” Fischer summarizes. “In the end, we now have enough data to test the effects on patients. This is a classic example of how fundamental research can pave the way for clinical studies.”
Based on these results, a DZNE clinical study involving patients in the early stages of Alzheimer’s disease is planned. This study is to begin very soon, and will also be supported by the “Alzheimer Stiftung Göttingen” of the University Medical Center Göttingen.
„Reinstating transcriptome plasticity and memory in models for cognitive decline”, Eva Benito, Hendrik Urbanke, Binu Ramachandran, Jonas Barth, Rashi Halder, Ankit Awasthi, Gaurav Jain, Vincenzo Capece, Susanne Burkhardt, Magdalena Navarro-Sala, Sankari Nagarajan, Anna-Lena Schütz, Steven Johnson, Stefan Bonn, Reinhardt Lührmann, Camin Dean, André Fischer, Journal of Clinical Investigation (2015), doi: 10.1172/JCI79942
Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research