Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug prevents seizure progression in model of epilepsy

07.05.2009
Carnegie Mellon University researchers have identified a new anticonvulsant compound that has the potential to stop the development of epilepsy. The findings are published in the current issue of the journal Epilepsia.
The research discovery builds on previous work identifying a specific molecular target whose increased activity is associated with seizure disorders, a potassium channel known as the BK channel.

"We have found a new anticonvulsant compound that eliminates seizures in a model of epilepsy," said Alison Barth, associate professor of biological sciences at Carnegie Mellon's Mellon College of Science. "The drug works by inhibiting ion channels whose role in epilepsy was only recently discovered. Understanding how these channels work in seizure disorders, and being able to target them with a simple treatment, represents a significant advance in our ability to understand and treat epilepsy."

Epilepsy is a neurological disorder marked by abnormal electrical activity in the brain that leads to recurring seizures. A person who has a first seizure is statistically much more likely to have a second, and with each subsequent seizure, the chance of having another seizure grows. A person is often diagnosed with epilepsy after having two or more seizures that have no other apparent cause.

In prior studies, Barth and colleagues were the first to link BK channels, ion channels that allow electrically charged potassium ions to move out of cells, to sporadic epilepsy. Previous studies had shown that these channels were genetically altered in a few rare individuals who suffer from the disease, but Barth and colleagues demonstrated that seizures themselves could lead to the same alterations in BK channel function.

Potassium ions move through the channels, starting and stopping the electrical impulses that allow neurons to communicate with one another. The Carnegie Mellon researchers found that after a first seizure, BK channel function was markedly enhanced. As a result, the neurons became overly excitable and were firing with more speed, intensity and spontaneity, leading Barth to believe that the abnormal increased activity of the channels might play a role in causing subsequent seizures and the emergence of epilepsy.

In the current study, Barth tested this theory by blocking the ion channels using a BK-channel antagonist called paxilline. Using an experimental model for epilepsy, Barth asked whether paxilline could reduce or prevent experimentally induced seizures, as it could normalize aberrant brain activity induced by previous seizures. Remarkably, Barth and colleagues Jesse Sheehan and Brett Benedetti discovered that the compound was effective at completely blocking subsequent seizures.

"The drug is orally available, and works in the low nanomolar range," said Barth, noting that these characteristics, which mean the drug is effective in low concentrations and can be taken as a pill, make it an especially promising compound for treatment in epilepsy patients. While most anticonvulsants currently used to treat epilepsy work to directly inhibit the activity of neurotransmitters that causes seizures, few compounds interact with specific ion channels, especially potassium channels. The researchers believe that targeting the BK channels and the abnormal brain activity that they induce might one day be used as a way to prevent the progression of seizure disorders over time, thus attacking the root cause of epilepsy.

According to Barth, the next steps will be to further investigate paxilline to see whether it is an effective anticonvulsant treatment for multiple types of seizures. The investigators continue to look at how BK channels are regulated by seizures to better understand the development of epilepsy.

Co-authors of the study include Sheehan and Benedetti, doctoral students in the Department of Biological Sciences and Center for the Neural Basis of Cognition at Carnegie Mellon. The study was funded by the National Institutes of Health, the Milken Family Foundation for Translational Research and the Alfred P. Sloan Foundation.

Jocelyn Duffy | EurekAlert!
Further information:
http://www.andrew.cmu.edu

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>