Navigation Links
Human stem cells predict efficacy of Alzheimer drugs
Date:12/6/2013

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. 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 Brstle, 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. Brstle'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. Brstle'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. Brstle. "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".


'/>"/>

Contact: Dr. Oliver Brüstle
r.neuro@uni-bonn.de
49-228-688-5500
University of Bonn
Source:Eurekalert  

Related medicine news :

1. New drug prevents spread of human prostate cancer cells
2. Scientists solving the mystery of human consciousness
3. First targeted nanomedicine to enter human clinical studies
4. Edith Mitchell, M.D., FACP, named 2012 recipient of ASCO Humanitarian Award
5. Novel compound demonstrates anti-leukemic effect in zebrafish, shows promise for human treatment
6. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
7. IBN discovers human neural stem cells with tumor targeting ability
8. RANK protein promotes the initiation, progression and metastasis of human breast cancer
9. CNIO researchers describe new functions of cohesin relevant for human disease
10. New Clues to the Evolution of the Human Brain
11. Humanist funerals
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Human stem cells predict efficacy of Alzheimer drugs
(Date:1/20/2017)... ... ... “The Land of More and More”: a brilliant story for children ... the simple and achievable answer. “The Land of More and More” is the creation ... in Angola, Indiana where he works with the children’s ministry department. , Michael ...
(Date:1/19/2017)... Los Angeles (PRWEB) , ... January 19, 2017 , ... ... Care Act will be repealed by Congressional political games that circumvent health needs of ... First Stand Rally” capture the human anxieties and needs government public servants were suppose ...
(Date:1/19/2017)... Ca (PRWEB) , ... January 19, 2017 , ... ... events for tech innovators, engineers, and scientists from around the world, announces the ... offers users a quick and easy portal to research breakthroughs and trending news, ...
(Date:1/19/2017)... ... January 19, 2017 , ... WholeHealth is announcing their participation ... Paziotopoulos, Andrew Petersen and Trish Henrie-Barrus will be present Saturday and Sunday in ... program. , “We know it’s easy to get carried away when you’re ...
(Date:1/19/2017)... ... January 19, 2017 , ... Bio-Optronics ... provides a modern CTMS workflow designed to seamlessly integrate and streamline the way ... to a single page, maximizing usability and improving efficiency significantly for users – ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 19, 2017 The U.S. Food and Drug Administration ... Constipation (CIC) in adult patients. "No one ... said Julie Beitz , M.D., director of the Office ... Evaluation and Research. "With the availability of new therapies, patients ... their condition." ...
(Date:1/19/2017)...  Stealth BioTherapeutics Inc. ( Stealth ), a clinical-stage ... announced new additions to its senior leadership team: ... and Daniel Geffken as interim Chief Financial ... , Pharm.D. has been promoted to Chief Clinical Development ... Doug and Daniel to our management team, as both ...
(Date:1/19/2017)... 19, 2017 James ... & Haematology, 2016;12(Suppl 2):3-8; http://www.touchoncology.com/articles/optimising-clinical-outcomes-gastrointestinal-cancers-through-inhibiting-angiogenesis-and ... ... Published recently in a supplement to European ... touchONCOLOGY, an article by James Gilbart ...
Breaking Medicine Technology: