Biomarkers for epilepsy

Epilepsy is a neurological condition that affects nearly fifty million people worldwide. It increases morbidity across all aspects of life and also presents an increased risk of premature mortality.

There are over 20 antiepileptic drugs (AEDs) licensed for treatment that successfully control seizures in most patients, improving their quality of life and permitting social re-integration. However, for nearly 30 % of patients AEDs are not effective, necessitating the development of new treatment modalities. Also, ideally interventions should be disease-modifying rather than merely controlling seizures.

The EU-funded EPIPGX (Epilepsy pharmacogenomics: delivering biomarkers for clinical use) study proposes to perform genome-wide analyses to identify genome-based biomarkers for epilepsy. The aim is to predict treatment response thereby improving the use of current AEDs and also identifying new therapy targets. Partners focused on the impact of the AEDs most commonly prescribed in the EU and those that incur huge healthcare costs.

During the initial phase of the project, scientists extracted data from over 5,000 clinical cases and genotyped nearly 8,000 samples. Genome-wide association studies for broad drug resistance and AED adverse reactions is also ongoing. Exome sequencing will also offer information on rare genetic variation that may influence AED treatment.

Collective analysis of these datasets should provide pharmacogenomic guidance to avoid serious adverse effects and help clinicians select the best-tolerated AEDs. Special emphasis will also be given on identifying biomarkers of teratogenesis that are associated with the use of the drug valproate in pregnancy.

Furthermore, the consortium is interested in developing an in silico method to predict the best treatments and outcomes for individual patients. This platform is anticipated to attract great interest from the industry.

Overall, the identification of biomarkers that can predict the pattern of response to AEDs will be of high clinical importance for people with newly-diagnosed and chronic epilepsy. In addition, it should optimise clinical management of people with epilepsy, improve treatment outcome and lead to new potential therapeutic targets.