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
New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center
Pain: Perception and motor impulses arise in the brain independently of one another
12.12.2018 | Technische Universität München
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
13.12.2018 | Awards Funding
13.12.2018 | Earth Sciences
13.12.2018 | Materials Sciences