Ancient Gene Unlocks Epilepsy Treatment Potential
Author: Penn State
Published: 2010/08/01 - Updated: 2025/11/28
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Neurological Disorders - Related Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research describes a scholarly study published in the peer-reviewed journal Nature Neuroscience examining how an ancient gene family regulates neuronal excitability and seizure thresholds in the brain. Scientists at Penn State University identified that the Kv12.2 potassium channel gene, which dates back approximately 542 million years to Cambrian-era sea creatures, plays a crucial role in maintaining the delicate balance between neuronal rest and excitement. Through experiments with mice, researchers demonstrated that animals lacking functional Kv12.2 genes experienced significantly lower seizure thresholds and frequent seizures, while blocking the channel in normal mice produced similar results.
This work is particularly valuable for individuals with epilepsy, caregivers, and the broader disability community because it opens new therapeutic pathways beyond current treatments - most epilepsy medications already target ion channels, but many cases result from environmental factors like brain injuries or fevers rather than inherited genetic defects. Understanding how potassium channels influence seizure thresholds could lead to more effective medications with fewer side effects, offering hope for the significant portion of patients whose seizures remain uncontrolled by existing drugs - Disabled World (DW).
- Definition: Epileptic Seizure
An epileptic seizure occurs when nerve cells in the brain fire electrical impulses at an abnormally rapid and uncontrolled rate, temporarily disrupting normal brain function and causing sudden changes in behavior, movement, sensation, or consciousness. Unlike isolated seizures that might result from fever, low blood sugar, or alcohol withdrawal, epileptic seizures are recurrent and unprovoked, stemming from an underlying tendency of the brain to produce these electrical disturbances. The manifestations vary widely depending on which part of the brain is affected - some people experience dramatic convulsions and loss of consciousness (generalized tonic-clonic seizures), while others may have brief lapses in awareness that last only seconds (absence seizures), or localized symptoms like involuntary jerking of one limb, unusual sensations, or altered emotions (focal seizures).
The seizure itself typically lasts from a few seconds to a couple of minutes, though the person may feel confused or fatigued for a period afterward. What distinguishes epilepsy from other conditions causing seizures is this pattern of recurring episodes without an immediate reversible cause, affecting roughly 1 in 26 people at some point in their lives and requiring ongoing management through medications, lifestyle adjustments, or in some cases surgical intervention.
Introduction
Ancient gene from 542 million years ago linked to epileptic seizures, offering new treatment pathways for both genetic and acquired seizure disorders.
New research points to a genetic route to understanding and treating epilepsy. Timothy Jegla, an assistant professor of biology at Penn State University, has identified an ancient gene family that plays a role in regulating the excitability of nerves within the brain.
"In healthy people, nerves do not fire excessively in response to small stimuli. This function allows us to focus on what really matters. Nerve cells maintain a threshold between rest and excitement, and a stimulus has to cross this threshold to cause the nerve cells to fire," Jegla explained. "However, when this threshold is set too low, neurons can become hyperactive and fire in synchrony. As excessive firing spreads across the brain, the result is an epileptic seizure."
Main Content
Managing this delicate rest-excitement balance are ion channels - neuronal "gates" that control the flow of electrical signals between cells. While sodium and calcium channels help to excite neurons, potassium channels help to suppress signaling between cells, increasing the threshold at which nerves fire. However, the genetic mechanisms that control the potassium channels and set this threshold are not fully understood. Jegla's team focused on a particular potassium-channel gene - called Kv12.2 - that is active in resting nerve cells and is expressed in brain regions prone to seizure. "We decided that Kv12.2 was a good candidate for study because it is part of an old gene family that has been conserved throughout animal evolution,"
Jegla said;
"This ancient gene family probably first appeared in the genomes of sea-dwelling creatures prior to the Cambrian era about 542-million years ago. It is still with us and doing something very important in present-day animals."
Previous studies have suggested that the Kv12.2 potassium channel has a role in spatial memory, but Jegla and his team focused on how it might be related to seizure disorders.
In collaboration with Jeffrey Noebels at Baylor College of Medicine, the team used an electroencephalography (EEG) device to monitor the brains of mice. They found that mice missing the Kv12.2 gene did indeed have frequent seizures, albeit without convulsions. The team then stimulated mice with a chemical that induces convulsive seizures. They found that normal mice had a much higher convulsive-seizure threshold than mice with a defective Kv12.2 gene. The team also found the same results when they used a chemical inhibitor to block the Kv12.2 potassium channel in normal mice.
"In mice without a functioning Kv12.2 gene, nerve cells had abnormally low firing thresholds. Even small stimuli caused seizures," Jegla explained. "We think that this potassium channel plays a role in the brain's ability to remain 'quiet' and to respond selectively to strong stimuli."
Jegla hopes to open up new avenues of epilepsy research by studying whether activation of the Kv12.2 potassium channel in normal animals can block seizures.
"Ion-channel defects have been identified in inherited seizure disorders, but many types of epilepsy don't have a genetic cause to begin with," Jegla explained. "They are often caused by environmental factors, such as a brain injury or a high fever. However, the most effective drugs used to treat epilepsy target ion channels. If we can learn more about how ion channels influence seizure thresholds, we should be able to develop better drugs with fewer side effects."
In addition to Jegla and Noebels, other scientists who contributed to this research include Xiaofei Zhang, Federica Bertaso, Karsten Baumgartel, and Sinead M. Clancy of the Scripps Research Institute; Jong W. Yoo of the Baylor College of Medicine; and Van Lee, Cynthia Cienfuegos, Carly Wilmot, Jacqueline Avis, Truc Hunyh, Catherine Daguia, and Christian Schmedt of the Genomics Institute of the Novartis Research Foundation. This research was funded by the National Institutes of Health through its National Institute for Neurological Disorders and Stroke.
Insights, Analysis, and Developments
Editorial Note: The implications of this Penn State discovery extend far beyond the laboratory, potentially reshaping how clinicians approach epilepsy treatment across diverse patient populations. While the genetic basis of some seizure disorders has been understood for decades, this work reveals a fundamental neurological mechanism that predates human evolution itself - a reminder that solutions to modern medical challenges may be encoded in our most ancient biology. What makes this research particularly promising is its dual relevance: it helps explain inherited epilepsy while simultaneously pointing toward therapeutic interventions for acquired seizure disorders caused by trauma, infection, or other environmental factors. The fact that a single gene family has been preserved across hundreds of millions of years of evolution underscores its critical importance to brain function, and suggests that therapies targeting this pathway might offer benefits with reduced risk of disrupting other essential neurological processes - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Penn State and published on 2010/08/01, this content may have been edited for style, clarity, or brevity.