Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Human Stem Cells Predict Efficacy of Alzheimer Drugs

06.12.2013
Why do certain Alzheimer medications work in animal models but not in clinical trials in humans?

A research team from the University of Bonn and the biomedical enterprise LIFE & BRAIN GmbH has been able to show that results of established test methods with animal models and cell lines used up until now can hardly be translated to the processes in the human brain.


Neural stem cells generated from iPS cells derived from a patient with Alzheimer’s disease.
(c) Foto: Jerome Mertens/Uni Bonn


This photo shows neurons generated from such neural stem cells. These are the cells, which were used for drug testing. They show the typical neuronal morphology with long processes.
(c) Foto: Jerome Mertens/Uni Bonn

Drug testing should therefore be conducted with human nerve cells, conclude the scientists. The results are published by Cell Press in the journal "Stem Cell Reports".

In the brains of Alzheimer patients, deposits form that consist essentially of beta-amyloid and are harmful to nerve cells. Scientists are therefore searching for pharmaceutical compounds that prevent the formation of these dangerous aggregates. In animal models, certain non-steroidal anti-inflammatory drugs (NSAIDs) were found to a reduced formation of harmful beta-amyloid variants. Yet, in subsequent clinical studies, these NSAIDs failed to elicit any beneficial effects.

"The reasons for these negative results have remained unclear for a long time", says Prof. Dr. Oliver Brüstle, Director of the Institute for Reconstructive Neurobiology of the University of Bonn and CEO of LIFE & BRAIN GmbH. "Remarkably, these compounds were never tested directly on the actual target cells – the human neuron", adds lead author Dr. Jerome Mertens of Prof. Brüstle's team, who now works at the Laboratory of Genetics in La Jolla (USA). This is because, so far, living human neurons have been extremely difficult to obtain. However, with the recent advances in stem cell research it has become possible to derive limitless numbers of brain cells from a small skin biopsy or other adult cell types.

Scientists transform skin cells into nerve cells

Now a research team from the Institute for Reconstructive Neurobiology and the Department of Neurology of the Bonn University Medical Center together with colleagues from the LIFE & BRAIN GmbH and the University of Leuven (Belgium) has obtained such nerve cells from humans. The researchers used skin cells from two patients with a familial form of Alzheimer's Disease to produce so-called induced pluripotent stem cells (iPS cells), by reprogramming the body's cells into a quasi-embryonic stage. They then transformed the resulting so-called "jack-of-all-trades cells" into nerve cells.

Using these human neurons, the scientists tested several compounds in the group of non-steroidal anti-inflammatory drugs. As control, the researchers used nerve cells they had obtained from iPS cells of donors who did not have the disease. Both in the nerve cells obtained from the Alzheimer patients and in the control cells, the NSAIDs that had previously tested positive in the animal models and cell lines typically used for drug screening had practically no effect: The values for the harmful beta-amyloid variants that form the feared aggregates in the brain remained unaffected when the cells were treated with clinically relevant dosages of these compounds.

Metabolic processes in animal models differ from humans

"In order to predict the efficacy of Alzheimer drugs, such tests have to be performed directly on the affected human nerve cells", concludes Prof. Brüstle’s colleague Dr. Philipp Koch, who led the study. Why do NSAIDs decrease the risk of aggregate formation in animal experiments and cell lines but not in human neurons? The scientists explain this with differences in metabolic processes between these different cell types. "The results are simply not transferable", says Dr. Koch.

The scientists now hope that in the future, testing of potential drugs for the treatment of Alzheimer’s disease will be increasingly conducted using neurons obtained from iPS cells of patients. "The development of a single drug takes an average of ten years", says Prof. Brüstle. "By using patient-specific nerve cells as a test system, investments by pharmaceutical companies and the tedious search for urgently needed Alzheimer medications could be greatly streamlined".

Publication: APP Processing in Human Pluripotent Stem Cell-Derived Neurons is Resistant to NSAID-Based Gamma-Secretase Modulation, Stem Cell Reports, DOI: 10.1016/j.stemcr.2013.10.011

Contact:

Prof. Dr. Oliver Brüstle
Institute for Reconstructive Neurobiology
Life & Brain Center
University of Bonn
Tel. ++49-228-6885500
E-Mail: r.neuro@uni-bonn.de

Johannes Seiler | idw
Further information:
http://www.uni-bonn.de

More articles from Health and Medicine:

nachricht NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University

nachricht How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

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,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>