Targeted Resequencing of Epilepsy Genes: A Pharmaco-Therapeutic Perspective

It has been estimated that more than half of all epilepsies have some genetic basis and over the pastdecade important progresses have been made in the understanding of the genetic causes of many ofthese epilepsies. Single gene defects in ion channels or neurotransmitter receptors are associated withsome inherited forms of epilepsy [1-6]. In addition, genetic discoveries in the field of infantile epilepsy syndromes have highlighted the possible different aetiologies other than channelopathies can result in epilepsy [7]. The importance of genetic testing has been highlighted inclinical contexts where the identification of a specific cause may clarify the prognosis, identify the bestavailable treatment, and define the risk of recurrence for current and future family members and avoidinvasive and or prolonged diagnostic processes [8]. Moreover, genetic testing allows understanding therole of the mutation and its relationship with the phenotype, thus helping in the definition of points of action for future therapies. The lack of substantial and long-lasting relief of unprovoked seizures, regardless the introduction in the past 15 years of a wide number of secondgeneration antiepileptic drugs (AEDs), epitomizes the necessity of a paradigm shift including a massive effort in the clarification of certain genetic determinants of this chronic neurological disorder [9,10]. As far aspharmacological research is assimilatedin the domain of the “system biology” [11], the idea of designing high selective ligands for complex multi-factorial syndromes is losing its attractiveness and clinical usability [12]. In its place, the “network pharmacology” approach (Hopkins [13]) may permit to abandon the genetic reductionism and the magic bullets philosophy, shifting our attention towards magic shotguns aimed at discovering unexpected multiple drug targets and customized pharmacotherapies [14,15].