Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

Further reports about: Match Pediatric Testing Treatment neurofibromatosis tumor cells

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>