New Hope

Possible Epilepsy Link Uncovered

Carnegie Mellon neuroscientists have identified what may be the first known common denominator underlying two types of epilepsy. Their findings offer new hope to people suffering from the disease.

It turns out that a disruption in the "BK ion channel" is the link. Not a science major? Ions are charged atoms or molecules, and ion channels regulate the flow of ions across the membrane inside every cell in the body. In the search for new drug therapies, ion channels are a favorite target because they're involved in a wide range of the body's biological processes.

Although BK channels have been linked to a rare, familial form of epilepsy, their involvement in other types of seizure disorders has never before been demonstrated. The new findings are published in the June issue of Neurobiology of Disease.

The researchers discovered that BK channels become abnormally active after a seizure. This disruption results in the neurons becoming overly excitable, which may be associated with the development of epilepsy. Carnegie Mellon scientists were able to reverse this abnormal excitability using a BK channel antagonist, which returned the post-seizure electrical activity to normal levels.

"The fact that the BK channel previously has been linked with familial epilepsy and with generalized seizures in subjects without a genetic predisposition points to a common therapeutic pathway," said Alison Barth, an associate professor of biological sciences at Carnegie Mellon's Mellon College of Science.

She added, "We've shown that BK antagonists can be very effective in normalizing aberrant electrical activity in neurons, which suggests that BK channel antagonists might be a new weapon in the arsenal against epilepsy."

Epilepsy is a neurological disorder marked by abnormal electrical activity in the brain that leads to recurring seizures. According to the Epilepsy Foundation, no cause can be found in about seven out of 10 people with epilepsy.

However, researchers have identified a genetic component in some types of epilepsy. This study establishes, for the first time, a shared component between different types of epilepsy.

"Although research has revealed that many types of inherited epilepsy are linked to mutations in different ion channels, there has been little overlap between these ion channels and those channels that are affected by sporadic or acquired forms of epilepsy," Barth said. "BK channels could represent a common pathway activated in familial and sporadic cases of epilepsy."

Co-authors of the study include Sonal Shruti and Roger L. Clem, graduate students in the Department of Biological Sciences and the Center for the Neural Basis of Cognition at Carnegie Mellon. The study was funded by the Sloan Foundation, the Milken Family Foundation, the National Institutes of Health and Carnegie Mellon University.

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