Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New therapeutic target identified in inherited brain tumor disorder


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:

More articles from Health and Medicine:

nachricht Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital

nachricht Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

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...

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

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>