EPIPGX · Epilepsy Pharmacogenomics: delivering biomarkers for clinical use

The purpose of the project is to identify genome-based biomarkers for use in clinical practice to individualise treatment of epilepsy, and stratify patients for clinical trials, aiming to avoid chronicity, prevent relapse and reduce adverse drug reactions (ADRs).The need for improved treatments in epilepsy is undoubted. Epilepsy is affects 50,000,000 people of all ages worldwide. Epilepsy is serious, increasing morbidity across all aspects of life, including a high risk of premature mortality. Over 20 antiepileptic drugs (AEDs) are licenced for its treatment. Seizures can be effectively controlled by AEDs in ~70% of people. Control of seizures leads to risk reduction for most of consequences of epilepsy, improves quality of life, permits social re-integration and leads to direct economic benefits. However, in 30% of patients, currently-available AEDs do not control seizures – recurrent seizures threaten life and impair its quality in these patients, and account for much of the €15.5 billion annual cost of epilepsy in the EU alone; there is currently no way to predict which patients will not respond to any or all AEDs; even in the 70% who do respond, only 47% respond to the first AED – whilst the correct drug is being sought, risks from seizures continue – we need to be able to predict the right drug for an individual from the outset; unrelated to responder status, AEDs can cause serious ADRs – a biomarker exists for only one ADR; there is a clear need for novel means of discovery of new AEDs – existing AEDs are anti-seizure drugs, not disease-modifying drugs.We will use genome-wide analyses, including next-generation sequencing, in large, well-phenotyped patient cohorts to identify genome-based biomarkers, to improve use of current AEDs and identify new therapy targets.SMEs, which are central to this project, will be able to take the data forward for development of clinical tests; data will also be invaluable for industry seeking to develop new treatments.