About 3.4 million Americans, or 1.2 % of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 % of patients with epilepsy, continue to have seizures even after trying multiple anti-seizure drugs.
Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it. A team led by Ashok K. Shetty, PhD, a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, associate director of the Institute for Regenerative Medicine and a research career scientist at the Olin E.
Teague Veterans' Medical Center, part of the Central Texas Veterans Health Care System, is working on a better and permanent treatment for epilepsy. Their results published this week in the Proceedings of the National Academy of Sciences (PNAS).
Seizures are caused when the excitatory neurons in the brain fire too much and inhibitory neurons the ones that tell the excitatory neurons to stop firing are not as abundant or aren't operating at their optimal level. The primary inhibitory neurotransmitter in the brain is called GABA, short for gamma-Aminobutyric acid. Over the last decade, scientists have learned how to create induced pluripotent stem cells from ordinary adult cells, like a skin cell.
These stem cells can then be coaxed to become virtually any type of cells in the body, including neurons that use GABA, called GABAergic interneurons."What research did is transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy," Shetty said.
The hippocampus is a region in the brain where seizures originate in temporal lobe epilepsy, which is also important for learning, memory, and mood. "It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy. "Further testing showed that these transplanted human neurons formed synapses, or connections, with the host excitatory neurons.
"They were also positive for GABA and other markers of specialized subclasses of inhibitory interneurons, which was the goal," Shetty said. "Another fascinating aspect of this study is that transplanted human GABAergic neurons were found to be directly involved in controlling seizures, as silencing the transplanted GABAergic neurons resulted in an increased number of seizures."
"This publication by Dr. Shetty and his colleagues is a major step forward in treating otherwise incurable diseases of the brain," said Darwin J. Prockop, MD, Ph.D., the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas