Enhanced Epilepsy Therapy with Genetic Analysis

There are genetic differences between epilepsy patients that decide on whether medical treatment is successful or not. This is the result of a major study at the Vienna General Hospital. These new insights form the basis for an epilepsy therapy tailor-made for the needs of each individual patient. This study will be presented to the scientific community at the end of May at the largest European congress on epilepsy that will be taking place in Vienna this year.

As much as three percent of the population will contract epilepsy during the course of their lives. However, thanks to state-of-the-art medicines, two-thirds of all persons affected will be able to lead lives free of epileptic attacks, although one third respond less well to these drugs. These patients were the focus of a study with more than 630 test subjects carried out by the University Hospital of Neurology at the University Hospital of Neurology. This study was dedicated to unlocking the key to a phenomenon that has long since been known in this group of patients. Namely, why does the efficacy of drugs vary so strongly from one patient to the next? In the future, the results obtained from the study of Dr. Fritz Zimprich and his team will make it possible to make a dramatic improvement in the diagnosis of the efficacy of medical therapy.

We know that there are proteins that provide something akin to chemical detoxification and they are also to be found in the brain. These transport proteins ensure that potentially damaging substances are carried away from the cells. For a healthy organism, this protective mechanism makes a lot of sense. However, it can make it more difficult to treat diseased tissue with drugs because these proteins often transport medicines from the cells that are meant to cure them.

Dr. Zimprich, the head of the study, points out that “we have only known for a little while of the existence of these so-called multi-drug resistance proteins in the brain. We picked up on this by thinking that the known differences in drug efficacy from one epilepsy patient to another may be dependant upon how many of these proteins are active in the brain of each of these patients. In turn, the degree of activity may be impacted by minute variations in genes that code for these proteins.”

There are at least two of these genes since every person has a set of two chromosomes. In this study, they compared the genetic sequence (symbolised by the letters A, C, G and T) of a very specific subsection of this pair of genes. The surprising finding was that five out of six of these epilepsy patients respond very poorly to drugs if the sequence is CGC on both subsections.

Dr. Zimprich provides further interpretation of the importance of these results: “Now, we are aware of the fact that this special section does not have a direct impact on the way the transport proteins functions. However, we think that this section may be something akin to an internal regulator that has a co-determining effect on how much of the protein is produced.” In the future, we will be able to make reliable predictions on the efficacy of a medical therapy by analysing the pertinent gene sections of epilepsy patients. Beyond this, these insights will form the point of departure for future combined therapies where the transport proteins are switched off by additional therapeutic agents, thus augmenting the efficacy of traditional drugs.

Professor Christoph Baumgartner, the head of the Working Group for Clinical Epileptology, chairperson of the national organisational committee and Dr. Zimprich’s colleague, is especially proud that this study was concluded shortly before the 6th European Congress on Epileptology. “The European Congress of the International League against Epilepsy only takes place every two years and it will have its venue this year in Vienna from May 30 to June 3. This means that we will now be able to present this important research to the international scientific community in Vienna.”