Title: FUNCTIONAL GENOMICS AND NEUROBIOLOGY OF EPILEPSY: A BASIS FOR NEW THERAPEUTIC STRATEGIES
Acronym: EPICURE
Project number: LSH-037315
EC contribution: 9.883.259 €
Duration: 48 months
Starting date: 01/01/2007
Instrument: Integrated Project

Epilepsy is a serious and common neurological disorder characterized by recurrent seizures, due to abnormal synchronized neuronal discharges.
As many as 6 million people in Europe currently have active epilepsy that has major implications not only for health but also for independent living, education and employement, mobility, personal relationship, and prospects for insurance. The resulting economic burden has been estimated at 18 billions Euros per year (European White Paper on Epilepsy 2001). Although the European epileptological community has an important tradition of scientific research contributing by one third to the worldwide scientific production in the field, according to the conclusions of the European White Paper on Epilepsy (2001), it “lacks central coordination”. Epidemiological observations have led to the consensus that genetic factors play a central role, especially in the so-called idiopathic generalized epilepsies, and that maladaptive developmental processes also contribute to epileptogenesis (the development of epilepsy). Precisely what genetic factors are involved, and how they interact with developmental alterations, remains far from established. Moreover, their implication for understanding the principle of drug and other treatments of epilepsy are poorly understood.

The EPICURE integrated project aims at mobilizing the potential synergies of the European research groups to shed light on these questions. EPICURE aims in particular to take advantage of the potentially powerful insights into pathophysiological pathways provided by genetics, both by identifying disease-causing genes and by understanding the contribution of candidate genes to pharmacoresistance. EPICURE will take this forward by studying at molecular, cellular and network levels the consequences of mutations in ion channel genes, because these are intimately involved in neuronal signaling and the main targets of antiepileptic medication.

Fig. 1 Map of the European countries participating in EPICURE
with one (green), two (blu) and three or more (red) research groups

In parallel EPICURE will examine the plasticity that occurs in the brain and in individual neurons during epileptogenesis. EPICURE will maintain cohesion in this integrated project by following a number of themes that cut across the multidisciplinary approaches, in particular the principle that the membrane channels that determine and make use of Cl- and Na+ ion gradients for their function are central to neuronal excitability, circuit function and treatment with many of the available drugs. This justifies an effort in identifying the full impact of mutations of the underlying genes, establishing the degree to which drugs targeting these processes penetrate the brain, and understanding how the ion gradients in individual cells interact with developmental processes to determine neuronal excitability. In many cases EPICURE will build on existing European collaborative efforts, and in other cases EPICURE will establish links between groups working on common or cognate disciplines.