Stem cells will help in the treatment of epilepsy

For patients suffering from severe epilepsy often no medication is effective. However, a new method based on the implantation of stem cells will be able to stop the attacks, affecting their source.

Worldwide, about 50 million people suffer from epilepsy. The proportion of the total population with active epilepsy (i.e. with continuing seizures or need for treatment) is currently between 4 and 10 per 1,000 people.

Although most of them respond positively to drug treatment, between 20 and 40 percent of patients with epilepsy continue to experience seizures, despite various therapeutic approaches. Even when drugs are working, people may develop cognitive impairment, memory problems, and depression due to side effects of the drugs.

The disease occurs due to the fact that excitatory neurons are excessively activated, and inhibiting neurons either do not cope with their work, or their number is not enough to reduce the impulses. The most important neurotransmitter responsible for the process of inhibition of excitation in the brain is gamma-Aminobutyric acid (GABA).

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, is working to improve the treatment of epilepsy. Their results published December 17, 2018 in the Proceedings of the National Academy of Sciences (PNAS).

Over the past decade, scientists have learned to create induced pluripotent stem cells (iPSCs) from adult cells, such as skin cells. The development of these stem cells can be directed along any path. They can transform into any type of body cells, including neurons secreting GABA (GABAergic interneurons) as a transmitter.

The Shetty’s team injected 38 rats with a chemical that triggers a long seizure. The resulting brain damage causes the animals to have spontaneous seizures, starting from the hippocampus, over the next few months.

One week after brain damage, scientists implanted GABAergic interneurons into the hippocampus of about half of the animals. Five months later, this group of rats showed 70% fewer seizures than animals without cell transplantation.

“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”, – Shetty said

The hippocampus is a region of the brain where seizures occur during temporal lobe epilepsy. It also plays an important role in learning, regulation of mood and memory.

“It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy.”

Further research showed that human transplanted neurons formed synapses (connections) with 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, PhD, the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine. “One important aspect of the work is that the same cells can be obtained from a patient.”

This approach, called autologous transplantation, is patient-specific, which means that there will be no risk of rejection of new neurons, and the person will not need medications to prevent rejection.

“We will need to make sure that we’re doing more good than harm”, – Shetty said. “Going forward, we need to make sure that all of the cells transplanted have turned into neurons, because putting undifferentiated pluripotent stem cells into the body could lead to tumors and other problems.”

“A great deal of research is required before patients can be safely treated”, – Prockop said. “But this publication shows a way in which patients can someday be treated with their own cells for the devastating effects of epilepsy but perhaps also other diseases such as Parkinsonism and Alzheimer’s disease.”