Genetics of antiepileptic drug resistance.
OBJECTIVE
Drug resistance is an important clinical problem in epilepsy, affecting a substantial number of patients globally. Mechanisms underlying drug resistance need to be understood to develop rational therapies. Genetics offers one route to better understanding, and thus potentially treating, drug resistance.


RESULTS
Several important advances in epilepsy genomics and in understanding of drug resistance have occurred, on a background of rapid advances in genomic research across human diseases. An increasing number of genetic changes, ranging from point mutations to large chromosomal rearrangements, have been identified in patients with epilepsy, broadening our understanding of causation. Elegant experiments have been undertaken to explore the consequences of detected mutations. In some cases, there have been implications for drug resistance in epilepsy. However, much work remains to be done to better understand the interplay between genomics of disease (epilepsy), genomics of drug response (pharmacogenomics of antiepileptic drugs) and genomics of drug resistance.


CONCLUSIONS
Major developments in technologies and methodologies, evolving confidence in high-throughput and genome-wide approaches, and a continuing research effort into the genetics of inherited and sporadic epilepsies are beginning to uncover mechanisms that may contribute to drug resistance - there is reason for hope of better treatments to come.
Sisodiya
Sanjay M
SM
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK. sisodiya@ion.ucl.ac.uk
Marini
Carla
C
D000927:Anticonvulsants / Q000627:therapeutic use*; D002877:Chromosomes, Human; D004342:Drug Hypersensitivity / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics
D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels