New molecular mechanism offers hope for causal epilepsy treatments

Epilepsy is primarily treated symptomatically - that is, the majority of the available medications aim to suppress seizures without influencing the underlying causes of the disease. A research team from the Medical University of Vienna has now identified a molecular mechanism that may play a role in the development of seizures. These findings pave the way for research into and development of causal therapies that could go beyond the purely anti-seizure effect. The results have been published in the Journal of Neuroscience.

The research team led by Helmut Kubista and Matej Hotka (Center for Physiology and Pharmacology, Division of Neurophysiology and Neuropharmacology, MedUni Vienna) focused on a neuronal activity pattern that became known as paroxysmal depolarisation shifts (PDS). These are a form of increased electrical activity in nerve cells that can occur in the course of brain damage. Until now, researchers regarded PDS as a precursor of epileptic seizures, and some studies even suggested that they may represent components of epileptic seizures. It has only recently been hypothesized that PDS may actually play a role in the development of the disease itself. The MedUni Vienna scientists have not only been able to provide evidence for this suggestion, they have also revealed a potential mode of action.

To arrive at their recently published findings, the researchers examined the effects of PDS on nerve cells in a specially developed cell culture model. "Our observations revealed that PDS temporarily lead to a completely altered energy metabolism in the neurons of a specific brain region, the hippocampus," reports Helmut Kubista. This change initially activates a protective mechanism against further damage, but in the long term it paves the way for seizure-like electrical discharges.

65 million people affected worldwide

Epilepsy is a chronic neurological disorder that affects around 65 million people worldwide. The associated seizures are attributed to a disruption of the excitation control in brain cells. Both the congenital and the acquired form of epilepsy (usually as a result of brain damage) are treated primarily with medications that aim to suppress epileptic seizures. Due to the previous gaps in our knowledge about the development of epilepsy, strategies to prevent the development of the disease are lacking. The findings that have now been obtained have opened up a new approach to research and development of causal treatment options: "Our study identifies PDS as a possible target for intervention in the mechanisms of epilepsy and epileptic seizures. This could be relevant for the prevention of those forms of epilepsy that can arise from brain damage such as stroke, cerebral hemorrhage or craniocerebral trauma," says Helmut Kubista, looking ahead to further studies that are intended to continue the research path taken.