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
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy