title: Pharmacogenomics in epilepsy.
abstract: There is high variability in the response to antiepileptic treatment across people with epilepsy. Genetic factors significantly contribute to such variability. Recent advances in the genetics and neurobiology of the epilepsies are establishing the basis for a new era in the treatment of epilepsy, focused on each individual and their specific epilepsy. Variation in response to antiepileptic drug treatment may arise from genetic variation in a range of gene categories, including genes affecting drug pharmacokinetics, and drug pharmacodynamics, but also genes held to actually cause the epilepsy itself. From a purely pharmacogenetic perspective, there are few robust genetic findings with established evidence in epilepsy. Many findings are still controversial with anecdotal or less secure evidence and need further validation, e.g. variation in genes for transporter systems and antiepileptic drug targets. The increasing use of genetic sequencing and the results of large-scale collaborative projects may soon expand the established evidence. Precision medicine treatments represent a growing area of interest, focussing on reversing or circumventing the pathophysiological effects of specific gene mutations. This could lead to a dramatic improvement of the effectiveness and safety of epilepsy treatments, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Whilst much has been written about epilepsy pharmacogenetics, there does now seem to be building momentum that promises to deliver results of use in clinic.
authors.affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, and Epilepsy Society, Chalfont-St-Peter, Bucks, United Kingdom; Neuroscience Department, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Balestrini
authors.affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, and Epilepsy Society, Chalfont-St-Peter, Bucks, United Kingdom. Electronic address: s.sisodiya@ucl.ac.uk.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D057285:Precision Medicine / Q000379:methods
chemical_list: D000927:Anticonvulsants
keywords: Adverse drug reactions; Drug resistance; Drug response; Epilepsy; Pharmacodynamics; Pharmacogenomics; Pharmacokinetics; Precision medicine