You are here

Stem Cell-Derived Neurons Stop Seizures

Comment

Discuss

BRYAN, TX (US), December 2018 — About 3.4 million Americans have active epilepsy. The majority respond to medication, but up to 40 percent 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, Ph.D., a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine and associate director of the Institute for Regenerative Medicine,  is working on a better and permanent treatment for epilepsy. Their results were published recently 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 — aren't as abundant or aren't operating at their optimal level. The main 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 we did is transplant human-induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy," Dr. 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," Dr. 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."

Dr. Shetty cautioned that these tests were early interventions after the initial brain injury induced by status epilepticus, which is a state of continuous seizures lasting more than five minutes in humans. The next step is to see if similar transplants would work for cases of chronic epilepsy, particularly drug-resistant epilepsy.

"Currently, there is no effective treatment for drug-resistant epilepsy accompanying with depression, memory problems, and a death rate five to 10 times that of the general population," he said. "Our results suggest that induced pluripotent stem cell-derived GABAergic cell therapy has the promise for providing a long-lasting seizure control and relieving co-morbidities associated with epilepsy."

Learn more:
https://vitalrecord.tamhsc.edu/stem-cell-derived-neurons-stop-seizures-improve-cognitive-function/
DOI: 10.1073/pnas.1814185115