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
Electrical 'switch' in brain's capillary network monitors activity and controls blood flow
27.03.2017 | Larner College of Medicine at the University of Vermont
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Health and Medicine
27.03.2017 | Life Sciences
27.03.2017 | Earth Sciences