About 1.2 percent of the population have active epilepsy. Although the majority of the people respond to anti-seizure medications, these medications may not work for every person. They may come with a risk of side effects. About 20 to 40 percent of patients with epilepsy continue to have seizures even after various anti-seizure medications.
Even when the drugs work, individuals may develop memory difficulties and depression. It may be due to the combination of the underlying seizure disorder and the drugs used to treat it.
A research team was led by Ashok K. Shetty. He is a Ph.D. professor at the Texas A&M College of Medicine. He is working on a permanent and better treatment for epilepsy. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).
“This publication by Dr. Shetty and his team is a step forward in treating incurable diseases of the brain,” said Darwin J. Prockop. He is an MD, Ph.D., the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine.
Working of excitatory and inhibitory neurons
Seizures are caused by the over-excitation of the excitatory neurons in the brain. Due to this overexcitation, they fire too much. And inhibitory neurons aren’t as abundant or aren’t effective at their optimum level.
Inhibitory neurons are required to stop the firing of excitatory neurons. Thus, the chief inhibitory neurotransmitter present in the brain is GABA, short for gamma-Aminobutyric acid.
Over the last decade, researchers have learned to generate induced pluripotent stem cells from normal adult cells, like a skin cell. Therefore, these stem cells can develop into nearly any type of cells in the body, including neurons which use GABA, called GABAergic interneurons.
“For this, 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 an area in the brain where seizures originate in temporal lobe epilepsy. It is also important for learning, mood, and memory. “Also, this region of brain functioned very well to overwhelm seizures. It even improves mental as well as mood functioning in the chronic epilepsy phase.”
Outcomes of the research
Additional testing exposed that the transplanted human neurons formed synapses with the excitatory neurons of the host. “They were also helpful for GABA and other markers of specific subclasses of inhibitory interneurons,” Shetty said.
“Another captivating aspect of this research is that transplanted human GABAergic neurons were found to be involved directly in controlling seizures. As silencing the transplanted GABAergic neurons caused an increased number of seizures.”
“One central aspect of the effort is that the similar cells can be attained from a patient.” This process, called autologous transplant, is patient specific. It means that there would be no rejection risk of the new neurons. And the person would not need anti-rejection drugs.
“However, we should make sure that we’re doing more good than harm,” Shetty said. “Going onward, we need to be certain that all the transplanted cells have turned into neurons. Because putting undifferentiated pluripotent stem cells could lead to tumors and other problems in the body.”
The epilepsy development often occurs after a head injury. That is why the Department of Defense is involved in funding the development of improved treatment and prevention options.
Treatment of other disorders
“Therefore, good research is essential before patients can be treated safely,” Prockop said. “But this study shows a technique through which patients can someday be treated with their own cells for the shocking epilepsy effects but possibly also other disorders like Parkinsonism and Alzheimer’s disease.”
Hence, Shetty advised that these tests were early interferences after the initial brain injury caused by status epilepticus. This is a state of continuous seizures in humans lasting more than five minutes.
The next phase is to understand if similar transplants would work for chronic epilepsy cases, mainly drug-resistant epilepsy. “Presently, there is no effective treatment for drug-resistant epilepsy. It is associated with memory problems, depression, and a death rate 5 to 10 times that of the general population,” he said.
“Hence, our findings propose that induced pluripotent stem cell-derived GABAergic cell therapy has the potential for providing a lifelong seizure control and releasing co-morbidities associated with epilepsy.”