Seizures affect 3% of all people across their lifespan and are the most common severe neurological condition. Epilepsy is an umbrella term for a variety of conditions characterised by seizures. Besides brain lesions, tumours and traumatic head injury as causes there is also a strong genetic component involved.

Unfortunately, treatment options are still limited. While some patients respond immediately to available drugs, about one quarter are not helped by any medication and only face the adverse drug reactions, such as weight gain, liver dysfunctions or psychiatric conditions. Specific genes have been linked to adverse drug reactions in the form of a severe rash, a life-threating condition called Steven-Johnson-syndrome.

Unravelling the interactions of drugs and genetics EpiPGX aims to understand why only some patients can be treated successfully. It is therefore investigating how the genetic makeup influences the response to different existing medications. Unravelling the interactions of drugs and genetics could in the long run personalise treatment and reduce ill-effects of anti-epileptic drugs.

Although seizures occur frequently in the population, epilepsy is not one singular condition. It describes a wide range of seizure types, frequency and severity, all of which are known to influence the therapeutic outcome.

The FP7 framework is essential for achieving this goal since only such a pan-European project allows gathering a significant number of epilepsy patients. Combining efforts within EpiPGX, with its total funding volume of €6 million, allows statistically significant numbers of patients, for several patient groups, to be brought together.

Interpreting genome data

EpiPGX has established common standards to extract the relevant data from existing clinical reports. Patient data is shared in depersonalised form so that only the treating clinician knows the patient who has consented to the study.

The real challenge lies in the interpretation: reading the sequence of a genome leads to a large number of variants between any two individuals – in the order of 30,000 positions between two unrelated Europeans. A “disease gene” – a gross simplification anyway – cannot be identified by reading the sequence alone.

Identifying a singular gene leading to a change in e.g. drug metabolism requires the utilisation of knowledge from biomedical and biological literature, a special focus of the LCSB’s Bioinformatics Core.

An individual variant of a gene might predispose for a particular reaction to drug treatment but genes do not work alone. All genes interact in multiple ways in living organisms. These interactions might be disturbed and lead to conditions such as epilepsy. Detecting the combination of variants that  influence each other is challenging on all levels from computation to  experimental validation and methods for identifying them are in constant development which several groups at the LCSB contribute to with expert
knowledge in statistics, machine learning and biological data analysis.

EpiPGX joins the forces of scientists and clinicians across Europe to enhance the treatments of epilepsy using modern genetics methods. Overcoming language differences between the scientific disciplines requires more effort than those between scientists from different countries. In the second year of the project, the consortium is well underway to perform the first analyses with the aggregated data.