Epilepsy: controlling it through cell therapy

The results of a study suggest that GABAergic cell therapy derived from induced pluripotent stem cells offers the promise of providing permanent control of seizures and alleviating the co-morbidities associated with epilepsy

About 50 million people in the world suffer from epilepsy. This condition mainly affects children, adolescents and people over 65 years of age. In addition to genetic causes, epilepsy can arise because of oxygen deficiency during childbirth, or it can also be due to brain damage caused by strokes, brain tumors, traumatic brain injuries, drug and alcohol abuse or brain infections.

Epileptic crises are caused by sudden and recurrent episodes of seizures, due to an imbalance between two different types of neuronal cells within the brain. In particular, crises occur when the excitatory neurons cause an excessive and rapid sudden discharge of the other brain cells, due to changes or incorrect functioning of the inhibitory neurons, responsible precisely for the regulation of the excitatory neurons.

To date, epilepsy is treated through drugs, surgery and nutrition to try to decrease episodes of seizures.

In the study by Professor Ashok K. Shetty of the Department of Molecular and Cellular Medicine of Texas A&M College of Medicine, published in the journal Proceedings of the National Academy of Science (PNAS) together with his team of researchers, it is explained how they are working on a better and permanent treatment for those suffering from epilepsy.

Dr. Shetty has obtained induced pluripotent stem cells (iPSCs) by “forcing” the epithelial cells taken from patients themselves to regress into their primary cell state. Once this state is reached, iPSCs can be genetically manipulated to form any cell in the body, such as neuronal cells.

In particular, iPSCs have been induced into GABAergic neuronal cells, i.e. neuronal cells that use GABA, the brain’s main inhibitory neurotransmitter. The aim of Dr. Shetty and his team was in fact to “correct” the differences in expression of receptors, responsible for seizures, stating, «It worked very well in suppressing seizures and even in improving cognitive and humoral functions in the chronic phase of epilepsy». Further tests have shown that transplanted neurons have formed synapses, or connections, with excitatory neurons of the recipient.

While still being studied on an animal model, the publication of Dr. Shetty and his team represents an important step forward in the treatment of otherwise incurable brain diseases. In addition, one of the most relevant aspects of this study is that the cells can be obtained from the patient himself. This type of process, called autologous transplantation, is specific to the patient, which means that there would be no risk of rejection of transplanted neurons.

«Our results suggest that GABAergic cell therapy derived from induced pluripotent stem cells offers the promise of providing permanent control of seizures and alleviating the co-morbidities associated with epilepsy».

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