Featured Research

from universities, journals, and other organizations

New Therapeutic Target Identified In Inherited Brain Tumor Disorder

Date:
November 3, 2005
Source:
Washington University School of Medicine
Summary:
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 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).

Related Articles


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."

###

Dasgupta B, Yi Y, Hegedus B, Weber JD, Gutmann DH. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Research, November 1, 2005.

Funding from the U.S. Department of Defense supported this research.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School of Medicine. "New Therapeutic Target Identified In Inherited Brain Tumor Disorder." ScienceDaily. ScienceDaily, 3 November 2005. <www.sciencedaily.com/releases/2005/11/051103082455.htm>.
Washington University School of Medicine. (2005, November 3). New Therapeutic Target Identified In Inherited Brain Tumor Disorder. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2005/11/051103082455.htm
Washington University School of Medicine. "New Therapeutic Target Identified In Inherited Brain Tumor Disorder." ScienceDaily. www.sciencedaily.com/releases/2005/11/051103082455.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins