Featured Research

from universities, journals, and other organizations

Drug Prevents Abnormalities That Lead To Seizures, Mouse Study Shows

Date:
April 4, 2008
Source:
Washington University School of Medicine in St. Louis
Summary:
Current medications for seizures are comparable to over-the-counter cold and flu remedies: They block symptoms, but don't significantly affect the underlying illnesses that cause them. Now scientists have taken the first step toward developing another option. They've used a drug to prevent the brain abnormalities that lead to seizures in mice with an inherited form of epilepsy.

Current medications for seizures are comparable to over-the-counter cold and flu remedies: They block symptoms, but don't significantly affect the underlying illnesses that cause them.

Now scientists at Washington University School of Medicine in St. Louis have taken the first step toward developing another option. They've used a drug to prevent the brain abnormalities that lead to seizures in mice with an inherited form of epilepsy.

Working in a mouse model of tuberous sclerosis, an inherited human condition that causes seizures, researchers showed that regular doses of the drug rapamycin prevented the mice from seizing. The treatment also blocked the development of structural abnormalities in the brain and extended lifespan.

"One percent of the general population has epilepsy, and one-third of those patients don't respond well to current treatments," says senior author Michael Wong, M.D., Ph.D., assistant professor of neurobiology and anatomy, of neurology and of pediatrics. "We need to look for new treatments that do more than just alleviate the symptoms. We have to find ways to prevent the underlying brain abnormalitites that lead to seizures, and this is a first step in that direction."

Epilepsy can be induced by dozens of different causes including various forms of brain injury, genetic mutations and exposure to environmental insults.

Tuberous sclerosis (TS) is one of the most common genetic causes of epilepsy. Epidemiologists estimate that it occurs in one birth in every 6,000. In addition to seizures, the condition may cause tumors in the brain and other organs, autism, learning disabilities, skin abnormalities and lung and kidney disease.

Scientists have linked TS to mutations in one of two genes, TSC1 or TSC2. To better understand and seek new treatments for tumors caused by TS, Wong's colleague and co-author David Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology and co-director of the neuro-oncology program at the Siteman Cancer Center, created a mouse model of TS.

Research by other scientists showed that the genes mutated in TS overactivate mTOR (mammalian target of rapamycin), a protein that regulates several aspects of cell growth and proliferation. Those results led to clinical trials currently underway to see if rapamycin, an FDA-approved drug that has been in use for more than a decade, can block tumor growth by decreasing activation of the mTOR pathway.

"We reasoned that mTOR might also be abnormally regulating genes that produce neurotransmitter receptors, ion channels, and other proteins involved in brain cell communication, and that this might contribute to the seizures we see in TS patients," Wong says. "If that's the case, rapamycin should decrease the chance of seizures by decreasing mTOR activation."

The mouse line developed by Gutmann's lab normally starts having seizures at 1 to 2 months of age. When Ling-Hui Zeng, M.D., Ph.D., a postdoctoral fellow in Wong's lab, gave a group of the mice regular doses of rapamycin starting at 2 weeks of age, they were seizure-free. A closer look at the structure of brain cells in the treated mice revealed that the drug had prevented the development of structural and molecular abnormalities in brain cells known as astrocytes.

Normally the mice die at 3-4 months of age, but with regular rapamycin doses they were still alive at 6 months. At that point, Wong's laboratory took them off the rapamycin, and the mice started seizing for the first time.

In separate experiments, scientists found that giving rapamycin to mice later in their development could still partially reverse brain abnormalities and decrease seizures.

"These results support the initiation of clinical trials to test this drug's ability to alleviate seizures from tuberous sclerosis in human patients," says Wong.

Wong's follow-up plans focus on further studies of mTOR's links to seizures in TS. Because of mTOR's wide-ranging effects on a variety of proteins and pathways, Wong wants to identify new drug targets that are more directly responsible for triggering seizures in TS patients.

Journal reference: Zeng L-H, Xu L, Gutmann DH, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Annals of Neurology, advance online edition, April 3, 2008.

Funding from the National Institutes of Health and the Tuberous Sclerosis Alliance supported this research.


Story Source:

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


Cite This Page:

Washington University School of Medicine in St. Louis. "Drug Prevents Abnormalities That Lead To Seizures, Mouse Study Shows." ScienceDaily. ScienceDaily, 4 April 2008. <www.sciencedaily.com/releases/2008/04/080403212256.htm>.
Washington University School of Medicine in St. Louis. (2008, April 4). Drug Prevents Abnormalities That Lead To Seizures, Mouse Study Shows. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2008/04/080403212256.htm
Washington University School of Medicine in St. Louis. "Drug Prevents Abnormalities That Lead To Seizures, Mouse Study Shows." ScienceDaily. www.sciencedaily.com/releases/2008/04/080403212256.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
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:
from the past week

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