UA Researchers Identify Potential Drug Development Target for Epilepsy Seizures

TUSCALOOSA, Ala. — A team of scientists from The University of Alabama used worms to reel in information that they hope will lead to a greater understanding of cellular mechanisms that may be exploited to treat epilepsy.

In a new research report in the current edition of the journal GENETICS, the researchers explain how the transparent roundworm, C. elegans, helped them identify key “molecular switches” that control the transport of a molecule (gamma-aminobutyric acid or “GABA”) that, if manipulated within our cells, might prevent the onset of seizures.

“It is our hope that this work serves to accelerate the path toward the identification of genetic factors that cause a susceptibility to epilepsy,” said Dr. Guy A. Caldwell, associate professor of biological sciences at UA and co-author of the study. “Simultaneously, this work has the potential to uncover new avenues toward therapeutic development to control or prevent seizures in the future.”

To arrive at this finding, the researchers conducted experiments involving drugs known to affect neuronal activity in combination with DNA mutations in genetic factors shared between C. elegans and humans.

Changes in the worm’s neuronal activity led to repetitive convulsions believed to be similar to those experienced in epilepsy. These convulsions were observed under a microscope, and videos of those events were used to evaluate the severity of the neuronal changes.

At the same time, the researchers used a green fluorescent protein to “tag” or “label” the cellular locale and delivery of GABA in neurons. This tagging allowed the researchers to see the specific genetic factors that led to abnormal movement of GABA in neurons as they coincided with worm seizures and to make appropriate comparisons with worms from the control group.

“Although much more work must be done before new drugs can be developed for people, these findings could offer hope to people with this devastating and frustrating condition,” said Mark Johnston, editor-in-chief of GENETICS.

“It may be hard to believe, but the cellular processes that occur in these worms are likely to be similar to those in humans,” Johnston said. “This work has the potential to significantly advance our understanding of what causes seizures in people, and could point the way to eliminating or reducing seizures.”

The research was conducted in the lab of Drs. Guy and Kim Caldwell. Cody Locke, a UA graduate who worked in the Caldwell lab, and Bwarenaba Kautu, a UA graduate student, are co-primary authors of the report. Kalen  Berry and Kyle Lee, UA undergraduate researchers, are co-authors.  

Since 1916, GENETICS  has covered high quality, original research on a range of topics bearing on inheritance, including population and evolutionary genetics, complex traits, developmental and behavioral genetics, cellular genetics, gene expression, genome integrity and transmission, and genome and systems biology. GENETICS, the peer-reviewed, peer-edited journal of the Genetics Society of America is one of the world’s most cited journals in genetics and heredity.

UA’s department of biological sciences is part of the College of Arts and Sciences, the University’s largest division and the largest liberal arts college in the state. Students from the College have won numerous national awards including Rhodes Scholarships, Goldwater Scholarships and memberships on the USA Today Academic All American Team.