Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse model tightly matches pediatric tumor syndrome, will speed drug hunt

04.03.2008
Frustrated by the slow pace of new drug development for a condition that causes pediatric brain tumors, a neurologist at Washington University School of Medicine in St. Louis decided to try to fine-tune the animal models used to test new drugs.

Instead of studying one mouse model of the disease causing the brain tumors, the laboratory of David Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology, evaluated three. They "auditioned" the three models to see which was the best match for neurofibromatosis 1, a genetic condition that increases the risk of brain tumors and afflicts more than 100,000 people in the United States.

Animal models have long been used to explore the basic physiology underlying disease and to tentatively try out new remedies, but Gutmann believes that creating a tighter match between the animal models and the human disorder will allow more extensive and more accurate preclinical testing of potential therapies.

"If you think of how we move drugs from testing in the laboratory to testing in humans, this is an exciting step that's likely to speed the translation from bench to bedside," says Gutmann, the senior author of a report in the March 1 Cancer Research. "With more extensive preclinical testing in the mice, we can make sure a new drug is reaching its target protein in tumor cells, we can learn whether the drug is killing tumor cells or shutting off their growth, and we can get some indication of whether the drug is likely to have an adverse effect on the developing brain."

Gutmann is director of the Washington University Neurofibromatosis Center, which facilitates multidisciplinary neurofibromatosis research and is dedicated to developing better treatments to improve the lives of patients affected by the disorder. Fifteen to 20 percent of children with neurofibromatosis 1 develop brain tumors called gliomas that arise from brain cells known as glial cells. Gutmann's lab has studied a mouse model of neurofibromatosis 1 for several years to gain a better understanding of how defects in the NF1 gene cause gliomas.

For the new study, Gutmann and colleagues Joshua Rubin, M.D., Ph.D., assistant professor of pediatrics, neurology and of neurobiology, and Joel Garbow, Ph.D., research associate professor of radiology, compared three mouse brain tumor models of neurofibromatosis 1. One of the models was the line his lab has previously used to study basic tumor biology.

To compare the mouse lines to the human disorder, researchers analyzed where the mice developed tumors, determined how quickly the tumor cells were dividing, and assessed when the tumors ceased growing. Based on these criteria, they learned that the model they had used earlier most faithfully reproduced the important features of the human condition. Researchers hope that this means the model will also give them the most accurate picture of how human patients are likely to respond to new treatments.

To test this theory, they gave the mice doses of a chemotherapy agent, temozolomide, currently in use clinically. Temozolomide slowed the growth and reduced the size of tumors in the mice, as it does in human patients.

Next researchers gave the mice rapamycin, an experimental drug currently in clinical trials as a treatment for other cancers. They found the drug was not killing tumor cells but preventing them from growing while the mice received regular doses of the drug. Higher doses could shut off tumor growth in a more long-lasting fashion, but also produced harmful side effects.

Because the trials were in mice, researchers could use a variety of invasive techniques to learn additional details about the effects of the drugs. For example, brain development is ongoing in young children, making the introduction of drugs that kill cells or stop their replication cause for significant concern. The mouse model let researchers look at developmental hotspots in the brain to see if temozolomide or rapamycin was adversely affecting the creation of new brain cells. They found that neither drug was.

Gutmann plans to use the mouse model in a new collaborative network funded by the Children's Tumor Foundation. His group and four other labs will test a variety of compounds against specific tumor types found in individuals affected with neurofibromatosis 1.

"We want to learn if these new drugs work the same in all aspects of the disease," Gutmann says. "We will be using what we learn to provide an efficient, rigorous pipeline for moving promising new drugs from the laboratory to clinical trials."

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

Further reports about: Match Pediatric Testing Treatment neurofibromatosis tumor cells

More articles from Life Sciences:

nachricht Gold nanoclusters: new frontier for developing medication for treatment of Alzheimer's disease
17.02.2020 | Science China Press

nachricht Catalyst deposition on fragile chips
17.02.2020 | Ruhr-University Bochum

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Im Focus: Quantum fluctuations sustain the record superconductor

Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected

Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Gold nanoclusters: new frontier for developing medication for treatment of Alzheimer's disease

17.02.2020 | Life Sciences

Artificial intelligence is becoming sustainable!

17.02.2020 | Information Technology

Catalyst deposition on fragile chips

17.02.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>