Epilepsy is a common neurological disease that causes seizures due to abnormal brain activity. The seizures can affect the whole brain or just one part, and can last for a few seconds to a few minutes. Globally, around 65 million people are affected by epilepsy including 3 million people in the United States. The disorder is most common in children and older adults and, whilst there is no cure, there are strategies and medications which can be used to manage the disorder.
New research conducted by researchers at the University of Copenhagen Faculty of Health and Medical Sciences could pave the way for new treatments for the disorder. The researchers identified the neurons that are most affected by epilepsy, some of which have not previously been linked with epilepsy. The researchers believe that these neurons may contribute to the development of epilepsy (epileptogenesis) and could serve as targets for new anti-epilepsy drugs.
‘Our findings potentially allows for the development of entirely new therapeutic approaches tailored towards specific neurons, which are malfunctioning in cases of epilepsy. This could be a breakthrough in personalized medicine-based treatment of patients suffering from epileptic seizures,’ said Associate Professor Konstantin Khodosevich from the Biotech Research & Innovation Center (BRIC) at the Faculty of Health and Medical Sciences.
The researchers analyzed more than 117,000 individual neurons for their study which were isolated from brain tissue taken from patients who underwent operations at the Danish Epilepsy Surgery Programme at Rigshospitalet in Copenhagen. The patients have received various treatments for epilepsy, yet between 30% and 40% continue to have seizures, despite being provided with anti-seizure drugs.
Previous research into epilepsy involved studying neurons in brain tissue together, including healthy and diseased cells. That approach has made it difficult to identify new drug targets. The latest study split the neurons into individual cells, with single cell analysis techniques used to identify the exact neurons that were affected by epilepsy.
The researchers were able to rate each neuron based on the degree to which it was affected, from neurons that were unaffected to those most affected. With that knowledge, researchers can now try to identify molecules that have a therapeutic effect on the neurons most affected by epilepsy which could inhibit the generation of seizures and return neuronal activity to normal levels. Research is continuing to identify the functional changes in the neurons that lead to epileptic seizures.
‘We show that the complexity of gene expression in epilepsy is much larger than previously known. It is not a matter of a handful or a few hundred genes changing,” said Khodosevich. “Our study proves that thousands of genes in different neurons change their expression in epilepsy. From these thousands of gene expression changes, we identified those that most likely contribute to epileptogenesis. Now it is time to prove it functionally.”
You can read more about the study in the paper – Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis – which was recently published in the journal Nature Communications. DOI: 10.1038/s41467-020-18752-7