Featured Research

from universities, journals, and other organizations

Gene Therapy Inhibits Epilepsy In Animals

Date:
November 9, 2006
Source:
Children's Hospital of Philadelphia
Summary:
For the first time, researchers have inhibited the development of epilepsy after a brain insult in animals. By using gene therapy to modify signaling pathways in the brain, neurology researchers found that they could significantly reduce the development of epileptic seizures in rats. "We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop," said one of the lead researchers.

For the first time, researchers have inhibited the development of epilepsy after a brain insult in animals. By using gene therapy to modify signaling pathways in the brain, neurology researchers found that they could significantly reduce the development of epileptic seizures in rats.

"We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop," said one of the lead researchers, Amy R. Brooks-Kayal, M.D., a pediatric neurologist at The Children's Hospital of Philadelphia and associate professor of Neurology and Pediatrics at the University of Pennsylvania School of Medicine. "This provides a 'proof of concept' that altering specific signaling pathways in nerve cells after a brain insult or injury could provide a scientific basis for treating patients to prevent epilepsy."

Dr. Brooks-Kayal and Shelley J. Russek, Ph.D., of Boston University School of Medicine were senior authors of the study in the Nov. 1 Journal of Neuroscience.

Working in a portion of the brain called the dentate gyrus, the researchers focused on one type of cell receptor, type A receptors, for the neurotransmitter gamma-aminobutyric acid (GABA). When GABA(A) receptors are activated, they inhibit the repetitive, excessive firing of brain cells that characterizes a seizure. Seizures are thought to occur, at least in part, because of an imbalance between two types of neurotransmitters: the glutamate system, which stimulates neurons to fire, and the GABA system, which inhibits that brain activity.

GABA's inhibitory role is considered particularly important in the dentate gyrus because the dentate gyrus acts as a gateway for brain activity into the hippocampus, an area that is critical to generating seizures in temporal lobe epilepsy, the most common type of epilepsy in children and adults.

GABA(A) receptors are made up of five subunits--proteins that play important roles in brain development and in controlling brain activity. Previous animal research by Dr. Brooks-Kayal's group had found that rats with epilepsy had lower levels of the alpha1 subunits of these receptors and higher levels of alpha4 subunits. Therefore, the researchers used gene delivery to alter the expression of the alpha1 subunit to see if this would have an effect on later seizure development.

To carry the gene that alters the expression of the protein, they used an adeno-associated virus vector, injected into the rats' brains. The researchers later injected the rats with pilocarpine, a drug that causes status epilepticus (SE), a convulsive seizure, shortly after injection.

They then evaluated the rats for later development of spontaneous seizures or epilepsy, which usually occurs after an initial SE injury. Rats that had received the gene therapy had elevated levels of alpha1 proteins and either did not develop spontaneous seizures, or took three times as long to experience a spontaneous seizure, compared to rats that did not receive the delivered gene.

In this short-term study, said Dr. Brooks-Kayal, it was impossible to tell whether the increased alpha1 subunit levels were only suppressing seizures or whether they would permanently prevent epilepsy from developing.

"In people, an initial episode of SE or an injury such as severe head trauma is known to raise the risk of later developing epilepsy, so this study suggests that strategies aimed at modifying signaling pathways in the brain after such an insult may help prevent epilepsy," said Dr. Brooks-Kayal. "The approach would likely be different than in this proof-of-concept animal study that involved injecting agents directly into the brain. This study, does, however, lay the foundation for a potential drug therapy that might act on the same signaling pathways, to prevent epilepsy after a brain insult such as an episode of SE."

The National Institutes of Health and the American Epilepsy Society provided grant support that funded this study. The first author on the study was YogendraSinh H. Raol, Ph.D., of Children's Hospital. Other co-authors were John Wolfe, V.M.D., Ph.D., and Ingrid V. Lund of the University of Pennsylvania School of Medicine and Children's Hospital; Guojun Zhang, M.D., Ph.D., of Children's Hospital; and Sabita Bandyopadhyay and Daniel S. Roberts, Ph.D., of Boston University School of Medicine.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Cite This Page:

Children's Hospital of Philadelphia. "Gene Therapy Inhibits Epilepsy In Animals." ScienceDaily. ScienceDaily, 9 November 2006. <www.sciencedaily.com/releases/2006/11/061109094746.htm>.
Children's Hospital of Philadelphia. (2006, November 9). Gene Therapy Inhibits Epilepsy In Animals. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2006/11/061109094746.htm
Children's Hospital of Philadelphia. "Gene Therapy Inhibits Epilepsy In Animals." ScienceDaily. www.sciencedaily.com/releases/2006/11/061109094746.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. 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:
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