Featured Research

from universities, journals, and other organizations

Findings In Epilepsy Gene In Animals May Guide Treatment Directions For Infants

Date:
June 7, 2009
Source:
Children's Hospital of Philadelphia
Summary:
Researchers studying a difficult-to-treat form of childhood epilepsy called infantile spasms have developed a line of mice that experiences seizures with features closely resembling those occurring in human infants. These genetically engineered mice provide a new opportunity for scientists to test treatments that may benefit children.

Researchers studying a difficult-to-treat form of childhood epilepsy called infantile spasms have developed a line of mice that experiences seizures with features closely resembling those occurring in patients with infantile seizures. These genetically engineered mice provide a new opportunity for scientists to test treatments that may benefit children.

Related Articles


Approximately one out of every 100 infants has a seizure. Many of them go on to have epilepsy—characterized by recurrent seizures. One obstacle to developing better therapies for children has been the lack of a good animal model," said study leader Jeffrey A. Golden, M.D., pathologist-in-chief at The Children's Hospital of Philadelphia.

Golden's team described a new mouse model for infantile spasms in an online study in the journal Brain.

Infantile spasms are a type of seizure that occurs in an estimated 1 in 2000 to 1 in 6000 babies, with onset between ages three months and one year. During the seizures, infants have jerking movements and abnormal brain waves (seen on EEGs). "Children with infantile spasms often have a poor developmental outcome," said Golden. "Despite current treatment, many children with infantile spasms go on to develop lifelong epilepsy and varying degrees of mental retardation."

Finding a treatment for infantile spasms is crucial. "If we could better treat the infantile spasms, it is very possible some of these later problems could be prevented," added Golden.

Neurologists previously knew that mutations in Arx, the X-linked aristaless-related homeobox gene, were associated with abnormal brain development, neurocognitive problems, and with childhood neurological conditions involving seizures and spasms.

Golden's team developed genetically engineered mice in which the Arx gene was removed from interneurons, a type of brain cell that inhibits electrical firing in brain circuits. Removing the gene's role appears to have resulted in overexcited brain cells and seizures in the mice. The seizures resembled human infantile spasms. Equally exciting to the researchers, these mice had another brain wave abnormality similar to that found in children with infantile spasms--an abnormal background EEG.

"This is the first genetic model of a developmental epilepsy, and even more importantly, it was generated by mutating the same gene that can be found mutated in humans with infantile spasms," said Golden. In an unexpected development, the researchers found that half of the female mice carrying the mutation also developed seizures. Because the mutation occurs on the X chromosome, it was expected that male mice would have seizures, which was true, and that all the females would be unaffected carriers, which was not the case.

This discovery prompted the researchers to take a closer look at human families with an infantile spasms patient. They found that the patients' mothers (14 women) had experienced normal development. But of the patients' nine other relatives—sisters, aunts and a cousin—six had neurological problems, including four with epilepsy. The neurological problems included varying degrees of mental retardation or other learning disabilities. These findings, said Golden, will immediately change the evaluation and testing of women with mental retardation and epilepsy, particularly in families with other affected individuals.

This new finding will also assist genetic counselors in advising parents who already have a child with an Arx mutation and are contemplating having another child.

Going forward, Golden said, this new animal model provides an important tool: an opportunity to begin testing drugs in the mice to identify potential treatments for children. "We can screen existing drugs to see if they are effective against this type of epilepsy," said Golden, adding that understanding the biological mechanism by which infantile spasms develop may also lead to more specific treatments.

Golden and first author Eric D. Marsh, M.D., Ph.D., are both from Children's Hospital and the University of Pennsylvania. Other co-authors were Amy Brooks-Kayal, of the Children's Hospital, Denver and the University of Colorado; and faculty members of the University of Chicago; Vanderbilt University; the University of Rotterdam, Netherlands; and the University of Pennsylvania School of Medicine. The National Institutes of Health, the American Epilepsy Society/Milken Family Foundation and The Children's Hospital of Philadelphia provided funding support for this study.


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.


Journal Reference:

  1. Marsh et al. Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. Brain, 2009; 132 (6): 1563 DOI: 10.1093/brain/awp107

Cite This Page:

Children's Hospital of Philadelphia. "Findings In Epilepsy Gene In Animals May Guide Treatment Directions For Infants." ScienceDaily. ScienceDaily, 7 June 2009. <www.sciencedaily.com/releases/2009/06/090601121712.htm>.
Children's Hospital of Philadelphia. (2009, June 7). Findings In Epilepsy Gene In Animals May Guide Treatment Directions For Infants. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2009/06/090601121712.htm
Children's Hospital of Philadelphia. "Findings In Epilepsy Gene In Animals May Guide Treatment Directions For Infants." ScienceDaily. www.sciencedaily.com/releases/2009/06/090601121712.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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