Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New therapeutic target identified in inherited brain tumor disorder

02.11.2005


Researchers studying a mouse model of neurofibromatosis 1 (NF1), a genetic condition that causes childhood brain tumors, have found their second new drug target in a year, a protein called methionine aminopeptidase-2 (MetAP2).



An established drug, fumagillin, is already known to suppress the activity of MetAP2. Researchers at Washington University School of Medicine in St. Louis showed that fumagillin significantly slowed the rapid proliferation of cultured mouse brain cells that resulted from the loss of Nf1, the gene that causes neurofibromatosis 1. Evaluation of the ability of this class of drugs to control brain tumor growth in small animal models is planned.

"This agent and others like it have already been in clinical trials as treatments for other tumors, so if we find that fumagillin inhibits brain tumor growth in preclinical studies, it will be a much smaller leap to using these compounds in patients with NF1," says senior investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology at Washington University School of Medicine in St. Louis and co-director of the neuro-oncology program at the Siteman Cancer Center.


Neurofibromatosis 1 affects more than 100,000 people in the United States and is one of the most common tumor predisposition syndromes. Gutmann and his colleagues discovered that abnormally high levels of MetAP2 may be a distinguishing characteristic of brain tumors in patients with NF1. Analyses of other similar brain tumors did not reveal the high MetAP2 levels characteristic of tumors caused by NF1.

To identify MetAP2, Gutmann collaborated with Jason D. Weber, Ph.D., assistant professor of medicine and of cellular biology and anatomy at the Washington University Neurofibromatosis Center. The center facilitates multidisciplinary neurofibromatosis research and is dedicated to developing better treatments to improve the lives of patients affected with neurofibromatosis.

Researchers in Gutmann’s and Weber’s laboratories took samples of cerebrospinal fluid from wild-type mice and a genetically engineered mouse model of NF1. Using a technique called proteomic analysis, they looked at the number of times copies of any given protein were found in the fluid. The goal was to identify proteins whose levels were different in the spinal fluid of the mouse model compared to normal mice.

Gutmann and Weber previously used the genetically engineered mice for a proteomic analysis of astrocytes, the brain cells that often become cancerous in patients with NF1. That led to the finding that proteins in the mammalian target of rapamycin pathway (mTOR) are overactivated, suggesting that mTOR may be a promising target for future chemotherapy for NF1-associated brain tumors.

The new study’s results suggest that MetAP2 may be directly regulated by neurofibromin, the protein produced by the Nf1 gene.

Like the mTOR pathway proteins, MetAP2 is normally active in processes that regulate the production of proteins from RNA. Gutmann and Weber plan additional studies to determine how increased MetAP2 expression enables astrocyte growth and brain tumor development.

"The availability of a mouse model of NF1-associated brain tumors allows us to conduct experiments that we could never perform in humans that have already broadened our understanding of the function of the Nf1 gene," Gutmann says. "It’s highly likely that these new insights will lead to new treatments for NF1 patients."

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

More articles from Health and Medicine:

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

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: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>