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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Role of Potassium Ion Channels in Epilepsy: Focus on Current Therapeutic Strategies

Author(s): Rahul Khan, Pragya Chaturvedi, Prachi Sahu, Abhilash Ludhiadch, Paramdeep Singh, Gagandeep Singh and Anjana Munshi*

Volume 23, Issue 1, 2024

Published on: 27 January, 2023

Page: [67 - 87] Pages: 21

DOI: 10.2174/1871527322666221227112621

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Epilepsy is one of the prevalent neurological disorders characterized by disrupted synchronization between inhibitory and excitatory neurons. Disturbed membrane potential due to abnormal regulation of neurotransmitters and ion transport across the neural cell membrane significantly contributes to the pathophysiology of epilepsy. Potassium ion channels (KCN) regulate the resting membrane potential and are involved in neuronal excitability. Genetic alterations in the potassium ion channels (KCN) have been reported to result in the enhancement of the release of neurotransmitters, the excitability of neurons, and abnormal rapid firing rate, which lead to epileptic phenotypes, making these ion channels a potential therapeutic target for epilepsy. The aim of this study is to explore the variations reported in different classes of potassium ion channels (KCN) in epilepsy patients, their functional evaluation, and therapeutic strategies to treat epilepsy targeting KCN.

Methodology: A review of all the relevant literature was carried out to compile this article.

Results: A large number of variations have been reported in different genes encoding various classes of KCN. These genetic alterations in KCN have been shown to be responsible for disrupted firing properties of neurons. Antiepileptic drugs (AEDs) are the main therapeutic strategy to treat epilepsy. Some patients do not respond favorably to the AEDs treatment, resulting in pharmacoresistant epilepsy.

Conclusion: Further to address the challenges faced in treating epilepsy, recent approaches like optogenetics, chemogenetics, and genome editing, such as clustered regularly interspaced short palindromic repeats (CRISPR), are emerging as target-specific therapeutic strategies.

Keywords: Ion channels, KCN, epilepsy, antiepileptic drugs, genome editing, optogenetics, chemogenetics, genetic alteration.

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[1]
Zhang S, et al. Ion channels in epilepsy: blasting fuse for neuronal hyperexcitability. In:Epilepsy-Advances in Diagnosis and Therapy. IntechOpen 2019; pp. 1-12.
[http://dx.doi.org/10.5772/intechopen.83698]
[2]
Yang S, Zhang Z, Chen H, et al. Temporal variability profiling of the default mode across epilepsy subtypes. Epilepsia 2021; 62(1): 61-73.
[http://dx.doi.org/10.1111/epi.16759] [PMID: 33236791]
[3]
Avoli M, de Curtis M, Gnatkovsky V, et al. Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy. J Neurophysiol 2016; 115(6): 3229-37.
[http://dx.doi.org/10.1152/jn.01128.2015] [PMID: 27075542]
[4]
Chow CY, Absalom N, Biggs K, King GF, Ma L. Venom-derived modulators of epilepsy-related ion channels. Biochem Pharmacol 2020; 181: 114043.
[http://dx.doi.org/10.1016/j.bcp.2020.114043] [PMID: 32445870]
[5]
Stefani A. Spadoni, Bernardi G. Voltage-activated calcium channels: targets of antiepileptic drug therapy? Epilepsia 1997; 38(9): 959-65.
[http://dx.doi.org/10.1111/j.1528-1157.1997.tb01477.x] [PMID: 9579933]
[6]
Zhang X, Velumian AA, Jones OT, Carlen PL. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia 2000; 41(s1): 52-60.
[http://dx.doi.org/10.1111/j.1528-1157.2000.tb02173.x] [PMID: 10768302]
[7]
Niespodziany I, Leclère N, Vandenplas C, Foerch P, Wolff C. Comparative study of lacosamide and classical sodium channel blocking antiepileptic drugs on sodium channel slow inactivation. J Neurosci Res 2013; 91(3): 436-43.
[http://dx.doi.org/10.1002/jnr.23136] [PMID: 23239147]
[8]
Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M. Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol 2010; 9(4): 413-24.
[http://dx.doi.org/10.1016/S1474-4422(10)70059-4] [PMID: 20298965]
[9]
Barker BS, et al. Ion channels. In: Conn’s translational neuroscience. Elsevier 2017; pp. 11-43.
[http://dx.doi.org/10.1016/B978-0-12-802381-5.00002-6]
[10]
Graves TD. Ion channels and epilepsy. QJM 2006; 99(4): 201-17.
[http://dx.doi.org/10.1093/qjmed/hcl021] [PMID: 16495302]
[11]
Stafstrom CE. Persistent sodium current and its role in epilepsy. Epilepsy Curr 2007; 7(1): 15-22.
[http://dx.doi.org/10.1111/j.1535-7511.2007.00156.x] [PMID: 17304346]
[12]
Oyrer J, Maljevic S, Scheffer IE, Berkovic SF, Petrou S, Reid CA. Ion channels in genetic epilepsy: from genes and mechanisms to disease-targeted therapies. Pharmacol Rev 2018; 70(1): 142-73.
[http://dx.doi.org/10.1124/pr.117.014456] [PMID: 29263209]
[13]
D’Adamo MC, Catacuzzeno L, Di Giovanni G, Franciolini F, Pessia M. K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy. Front Cell Neurosci 2013; 7: 134.
[http://dx.doi.org/10.3389/fncel.2013.00134] [PMID: 24062639]
[14]
Villa C, Combi R. Potassium channels and human epileptic phenotypes: an updated overview. Front Cell Neurosci 2016; 10: 81.
[http://dx.doi.org/10.3389/fncel.2016.00081] [PMID: 27064559]
[15]
Gutman GA, Chandy KG, Grissmer S, et al. International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 2005; 57(4): 473-508.
[http://dx.doi.org/10.1124/pr.57.4.10] [PMID: 16382104]
[16]
Niday Z, Tzingounis AV. Potassium channel gain of function in epilepsy: an unresolved paradox. Neuroscientist 2018; 24(4): 368-80.
[http://dx.doi.org/10.1177/1073858418763752] [PMID: 29542386]
[17]
Heeroma JH, Henneberger C, Rajakulendran S, Hanna MG, Schorge S, Kullmann DM. Episodic ataxia type 1 mutations differentially affect neuronal excitability and transmitter release. Dis Model Mech 2009; 2(11-12): 612-9.
[http://dx.doi.org/10.1242/dmm.003582] [PMID: 19779067]
[18]
D’Adamo MC, Hasan S, Guglielmi L, et al. New insights into the pathogenesis and therapeutics of episodic ataxia type 1. Front Cell Neurosci 2015; 9: 317.
[http://dx.doi.org/10.3389/fncel.2015.00317] [PMID: 26347608]
[19]
Glasscock E, Yoo JW, Chen TT, Klassen TL, Noebels JL. Kv1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction as a candidate mechanism for sudden unexplained death in epilepsy. J Neurosci 2010; 30(15): 5167-75.
[http://dx.doi.org/10.1523/JNEUROSCI.5591-09.2010] [PMID: 20392939]
[20]
Miceli F, et al. Distinct epilepsy phenotypes and response to drugs in KCNA1 gain-and loss-of function variants. Epilepsia 2021.
[PMID: 34778950]
[21]
Rogers A, Golumbek P, Cellini E, et al. De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants. Am J Med Genet A 2018; 176(8): 1748-52.
[http://dx.doi.org/10.1002/ajmg.a.38840] [PMID: 30055040]
[22]
Miao P, Feng J, Guo Y, et al. Genotype and phenotype analysis using an epilepsy-associated gene panel in Chinese pediatric epilepsy patients. Clin Genet 2018; 94(6): 512-20.
[http://dx.doi.org/10.1111/cge.13441] [PMID: 30182498]
[23]
Eunson LH, Rea R, Zuberi SM, et al. Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol 2000; 48(4): 647-56.
[http://dx.doi.org/10.1002/1531-8249(200010)48:4<647:AID-ANA12>3.0.CO;2-Q] [PMID: 11026449]
[24]
Diani E, Di Bonaventura C, Mecarelli O, et al. Autosomal dominant lateral temporal epilepsy: Absence of mutations in ADAM22 and Kv1 channel genes encoding LGI1-associated proteins. Epilepsy Res 2008; 80(1): 1-8.
[http://dx.doi.org/10.1016/j.eplepsyres.2008.03.001] [PMID: 18440780]
[25]
Kearney JA. KCNA2-related epileptic encephalopathy. Pediatr Neurol Briefs 2015; 29(4): 27.
[http://dx.doi.org/10.15844/pedneurbriefs-29-4-2] [PMID: 26933568]
[26]
Hundallah K, et al. Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: expansion of the genotypic and phenotypic spectrum. european journal of paediatric neurology 2016; 20(4): 657-60.
[27]
Corbett MA, Bellows ST, Li M, et al. Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. Neurology 2016; 87(19): 1975-84.
[http://dx.doi.org/10.1212/WNL.0000000000003309] [PMID: 27733563]
[28]
Syrbe S, Hedrich UBS, Riesch E, et al. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat Genet 2015; 47(4): 393-9.
[http://dx.doi.org/10.1038/ng.3239] [PMID: 25751627]
[29]
Hedrich UBS, Lauxmann S, Wolff M, et al. 4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2 -encephalopathy. Sci Transl Med 2021; 13(609): eaaz4957.
[http://dx.doi.org/10.1126/scitranslmed.aaz4957] [PMID: 34516822]
[30]
Pena SDJ, Coimbra RLM. Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy. Clin Genet 2015; 87(2): e1-3.
[http://dx.doi.org/10.1111/cge.12542] [PMID: 25477152]
[31]
Masnada S, Hedrich UBS, Gardella E, et al. Clinical spectrum and genotype–phenotype associations of KCNA2-related encephalopathies. Brain 2017; 140(9): 2337-54.
[http://dx.doi.org/10.1093/brain/awx184] [PMID: 29050392]
[32]
Kessi M, Chen B, Peng J, et al. Intellectual disability and potassium channelopathies: a systematic review. Front Genet 2020; 11: 614.
[http://dx.doi.org/10.3389/fgene.2020.00614] [PMID: 32655623]
[33]
Choi BJ, Yoon JH, Choi WS, Kim O, Nam SW, Park WS. Genetic association of KCNA5 and KCNJ3 polymorphisms in Korean children with epilepsy. Mol Cell Toxicol 2014; 10(2): 223-8.
[http://dx.doi.org/10.1007/s13273-014-0024-9]
[34]
Allen NM, Conroy J, Shahwan A, et al. Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion. Epilepsia 2016; 57(1): e12-7.
[http://dx.doi.org/10.1111/epi.13250] [PMID: 26648591]
[35]
Thiffault I, Speca DJ, Austin DC, et al. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. J Gen Physiol 2015; 146(5): 399-410.
[http://dx.doi.org/10.1085/jgp.201511444] [PMID: 26503721]
[36]
Saitsu H, Akita T, Tohyama J, et al. De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. Sci Rep 2015; 5(1): 15199.
[http://dx.doi.org/10.1038/srep15199] [PMID: 26477325]
[37]
Calhoun JD, Vanoye CG, Kok F, George AL Jr, Kearney JA. Characterization of a KCNB1 variant associated with autism, intellectual disability, and epilepsy. Neurol Genet 2017; 3(6): e198.
[http://dx.doi.org/10.1212/NXG.0000000000000198] [PMID: 29264390]
[38]
Torkamani A, Bersell K, Jorge BS, et al. De novo KCNB1 mutations in epileptic encephalopathy. Ann Neurol 2014; 76(4): 529-40.
[http://dx.doi.org/10.1002/ana.24263] [PMID: 25164438]
[39]
Srivastava S, Cohen JS, Vernon H, et al. Clinical whole exome sequencing in child neurology practice. Ann Neurol 2014; 76(4): 473-83.
[http://dx.doi.org/10.1002/ana.24251] [PMID: 25131622]
[40]
de Kovel CGF, Brilstra EH, van Kempen MJA, et al. Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients. Mol Genet Genomic Med 2016; 4(5): 568-80.
[http://dx.doi.org/10.1002/mgg3.235] [PMID: 27652284]
[41]
Hawkins NA, et al. Epilepsy and neurobehavioral abnormalities in mice with a KCNB1 pathogenic variant that alters conducting and non-conducting functions of KV2. 1. bioRxiv 770206.2019;
[42]
Marini C, Romoli M, Parrini E, et al. Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations. Neurol Genet 2017; 3(6): e206.
[http://dx.doi.org/10.1212/NXG.0000000000000206] [PMID: 29264397]
[43]
de Kovel CGF, Syrbe S, Brilstra EH, et al. Neurodevelopmental disorders caused by de novo variants in KCNB1 genotypes and phenotypes. JAMA Neurol 2017; 74(10): 1228-36.
[http://dx.doi.org/10.1001/jamaneurol.2017.1714] [PMID: 28806457]
[44]
Bar C, Barcia G, Jennesson M, et al. Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature. Hum Mutat 2020; 41(1): 69-80.
[http://dx.doi.org/10.1002/humu.23915] [PMID: 31513310]
[45]
Muona M, Berkovic SF, Dibbens LM, et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet 2015; 47(1): 39-46.
[http://dx.doi.org/10.1038/ng.3144] [PMID: 25401298]
[46]
Barot N, Margiotta M, Nei M, Skidmore C. Progressive myoclonic epilepsy: myoclonic epilepsy and ataxia due to KCNC1 mutation (MEAK): a case report and review of the literature. Epileptic Disord 2020; 22(5): 654-8.
[http://dx.doi.org/10.1684/epd.2020.1197] [PMID: 32972906]
[47]
Carpenter JC, Männikkö R, Heffner C, et al. Progressive myoclonus epilepsy KCNC1 variant causes a developmental dendritopathy. Epilepsia 2021; 62(5): 1256-67.
[http://dx.doi.org/10.1111/epi.16867] [PMID: 33735526]
[48]
Oliver KL, Franceschetti S, Milligan CJ, et al. Myoclonus epilepsy and ataxia due to KCNC 1 mutation: Analysis of 20 cases and K + channel properties. Ann Neurol 2017; 81(5): 677-89.
[http://dx.doi.org/10.1002/ana.24929] [PMID: 28380698]
[49]
Park J, Koko M, Hedrich UBS, et al. KCNC1 -related disorders: new de novo variants expand the phenotypic spectrum. Ann Clin Transl Neurol 2019; 6(7): 1319-26.
[http://dx.doi.org/10.1002/acn3.50799] [PMID: 31353862]
[50]
Kim H, Lee S, Choi M, et al. Familial cases of progressive myoclonic epilepsy caused by maternal somatic mosaicism of a recurrent KCNC1 p.Arg320His mutation. Brain Dev 2018; 40(5): 429-32.
[http://dx.doi.org/10.1016/j.braindev.2018.01.006] [PMID: 29428275]
[51]
Mahale RR, et al. Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK): a cause of progressive myoclonic epilepsy. Acta Neurol Belg 2021; 1-3.
[PMID: 33725338]
[52]
Zhang J, et al. Three cases of progressive myoclonic epilepsy caused by KCNC1 gene mutations and literature review. Zhonghua Shiyong Erke Linchuang Zazhi 2019; 1876-81.
[53]
Munch AS, Saljic A, Boddum K, Grunnet M, Hougaard C, Jespersen T. Pharmacological rescue of mutated Kv3.1 ion-channel linked to progressive myoclonus epilepsies. Eur J Pharmacol 2018; 833: 255-62.
[http://dx.doi.org/10.1016/j.ejphar.2018.06.015] [PMID: 29894724]
[54]
Carpenter JC, Schorge S. The voltage-gated channelopathies as a paradigm for studying epilepsy-causing genes. Curr Opin Physiol 2018; 2: 71-6.
[http://dx.doi.org/10.1016/j.cophys.2018.01.004]
[55]
Nascimento FA, Andrade DM. Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations. Epileptic Disord 2016; 18(S2): 135-8.
[http://dx.doi.org/10.1684/epd.2016.0859] [PMID: 27629860]
[56]
Cameron JM, Maljevic S, Nair U, et al. Encephalopathies with KCNC1 variants: genotype-phenotype-functional correlations. Ann Clin Transl Neurol 2019; 6(7): 1263-72.
[http://dx.doi.org/10.1002/acn3.50822] [PMID: 31353855]
[57]
Kim SY, Jang SS, Kim H, et al. Genetic diagnosis of infantile-onset epilepsy in the clinic: Application of whole-exome sequencing following epilepsy gene panel testing. Clin Genet 2021; 99(3): 418-24.
[http://dx.doi.org/10.1111/cge.13903] [PMID: 33349918]
[58]
Zhang Y, Ali SR, Nabbout R, Barcia G, Kaczmarek LKA. KCNC1 mutation in epilepsy of infancy with focal migrating seizures produces functional channels that fail to be regulated by PKC phosphorylation. J Neurophysiol 2021; 126(2): 532-9.
[http://dx.doi.org/10.1152/jn.00257.2021] [PMID: 34232791]
[59]
Poirier K, Viot G, Lombardi L, Jauny C, Billuart P, Bienvenu T. Loss of Function of KCNC1 is associated with intellectual disability without seizures. Eur J Hum Genet 2017; 25(5): 560-4.
[http://dx.doi.org/10.1038/ejhg.2017.3] [PMID: 28145425]
[60]
Vetri L, Calì F, Vinci M, et al. A de novo heterozygous mutation in KCNC2 gene implicated in severe developmental and epileptic encephalopathy. Eur J Med Genet 2020; 63(4): 103848.
[http://dx.doi.org/10.1016/j.ejmg.2020.103848] [PMID: 31972370]
[61]
Lau D, de Miera EV-S, Contreras D, et al. Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci 2000; 20(24): 9071-85.
[http://dx.doi.org/10.1523/JNEUROSCI.20-24-09071.2000] [PMID: 11124984]
[62]
Rudy B, Chow A, Lau D, et al. Contributions of Kv3 channels to neuronal excitability. Ann N Y Acad Sci 1999; 868(1): 304-43.
[http://dx.doi.org/10.1111/j.1749-6632.1999.tb11295.x] [PMID: 10414303]
[63]
Rydzanicz M. Zwoliński P, Gasperowicz P, et al. A recurrent de novo variant supportsKCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy. Am J Med Genet A 2021; 185(11): 3384-9.
[http://dx.doi.org/10.1002/ajmg.a.62455] [PMID: 34448338]
[64]
Candelo E, et al. Identification of novel ADGRV1 and KCNC2 variants using whole-exome sequencing in two colombian patients with usher and encephalopathy syndromes 2021.
[http://dx.doi.org/10.21203/rs.3.rs-923411/v1]
[65]
Mehinovic E, et al. Germline mosaicism of a missense variant in KCNC2 in a multiplex family with autism and epilepsy. medRxiv 21264306.2021;
[http://dx.doi.org/10.1101/2021.12.06.21264306]
[66]
Mukherjee S, Cassini TA, Hu N, et al. Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused by de novo KCNC2 variants. HGG Adv 2022; 3(4): 100131.
[67]
Schwarz N, Simone S, Manuela P, et al. Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations. medRxiv 21257099.2021;
[http://dx.doi.org/10.1101/2021.05.21.21257099]
[68]
Dorn T, Riegel M, Schinzel A, Siegel AM, Krämer G. Epilepsy and trisomy 19q—different seizure patterns in a brother and a sister. Epilepsy Res 2001; 47(1-2): 119-26.
[http://dx.doi.org/10.1016/S0920-1211(01)00303-5] [PMID: 11673026]
[69]
Singh B, Ogiwara I, Kaneda M, et al. A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy. Neurobiol Dis 2006; 24(2): 245-53.
[http://dx.doi.org/10.1016/j.nbd.2006.07.001] [PMID: 16934482]
[70]
Lee H, Lin MA, Kornblum HI, Papazian DM, Nelson SF. Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet 2014; 23(13): 3481-9.
[http://dx.doi.org/10.1093/hmg/ddu056] [PMID: 24501278]
[71]
Zhang Y, Tachtsidis G, Schob C, et al. KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating. Hum Mol Genet 2021; 30(23): 2300-14.
[http://dx.doi.org/10.1093/hmg/ddab192] [PMID: 34245260]
[72]
Lee YC, Durr A, Majczenko K, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol 2012; 72(6): 859-69.
[http://dx.doi.org/10.1002/ana.23701] [PMID: 23280837]
[73]
Smets K, Duarri A, Deconinck T, et al. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy. BMC Med Genet 2015; 16(1): 51.
[http://dx.doi.org/10.1186/s12881-015-0200-3] [PMID: 26189493]
[74]
Yus-nájera E, Muñoz A, Salvador N, et al. Localization of KCNQ5 in the normal and epileptic human temporal neocortex and hippocampal formation. Neuroscience 2003; 120(2): 353-64.
[http://dx.doi.org/10.1016/S0306-4522(03)00321-X] [PMID: 12890507]
[75]
Nowacki TA, Jirsch JD. Evaluation of the first seizure patient: Key points in the history and physical examination. Seizure 2017; 49: 54-63.
[http://dx.doi.org/10.1016/j.seizure.2016.12.002] [PMID: 28190753]
[76]
Yang T, Chung SK, Zhang W, et al. Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndrome. Circ Arrhythm Electrophysiol 2009; 2(4): 417-26.
[http://dx.doi.org/10.1161/CIRCEP.109.850149] [PMID: 19808498]
[77]
Partemi S, Vidal MC, Striano P, et al. Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series. Int J Legal Med 2015; 129(3): 495-504.
[http://dx.doi.org/10.1007/s00414-014-1063-4] [PMID: 25119684]
[78]
Kim KW, Kim K, Kim HJ, Kim BI, Baek M, Suh BC. Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family. Proc Natl Acad Sci 2021; 118(47): e2110200118.
[http://dx.doi.org/10.1073/pnas.2110200118] [PMID: 34785595]
[79]
Weckhuysen S, Mandelstam S, Suls A, et al. KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012; 71(1): 15-25.
[http://dx.doi.org/10.1002/ana.22644] [PMID: 22275249]
[80]
Soldovieri MV, Boutry-Kryza N, Milh M, et al. Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A. Hum Mutat 2014; 35(3): 356-67.
[http://dx.doi.org/10.1002/humu.22500] [PMID: 24375629]
[81]
Chioza B, Osei-Lah A, Wilkie H, et al. Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes. Epilepsy Res 2002; 52(2): 107-16.
[http://dx.doi.org/10.1016/S0920-1211(02)00195-X] [PMID: 12458027]
[82]
Zara F, Specchio N, Striano P, et al. Genetic testing in benign familial epilepsies of the first year of life: Clinical and diagnostic significance. Epilepsia 2013; 54(3): 425-36.
[http://dx.doi.org/10.1111/epi.12089] [PMID: 23360469]
[83]
Miceli F, Striano P, Soldovieri MV, et al. A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability. Epilepsia 2015; 56(2): e15-20.
[http://dx.doi.org/10.1111/epi.12887] [PMID: 25524373]
[84]
Grinton BE, Heron SE, Pelekanos JT, et al. Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome. Epilepsia 2015; 56(7): 1071-80.
[http://dx.doi.org/10.1111/epi.13020] [PMID: 25982755]
[85]
Fusco C, Frattini D, Bassi MT. A novel KCNQ3 gene mutation in a child with infantile convulsions and partial epilepsy with centrotemporal spikes. Eur J Paediatr Neurol 2015; 19(1): 102-3.
[http://dx.doi.org/10.1016/j.ejpn.2014.08.006] [PMID: 25278462]
[86]
Lauritano A, Moutton S, Longobardi E, et al. A novel homozygous KCNQ3 loss-of-function variant causes non-syndromic intellectual disability and neonatal-onset pharmacodependent epilepsy. Epilepsia Open 2019; 4(3): 464-75.
[http://dx.doi.org/10.1002/epi4.12353] [PMID: 31440727]
[87]
Lehman A, Thouta S, Mancini GMS, et al. Loss-of-function and gain-of-function mutations in KCNQ5 cause intellectual disability or epileptic encephalopathy. Am J Hum Genet 2017; 101(1): 65-74.
[http://dx.doi.org/10.1016/j.ajhg.2017.05.016] [PMID: 28669405]
[88]
Krueger J, Schubert J, Kegele J, et al. Loss of function variants in the KCNQ5 gene are associated with genetic generalized epilepsies. Bio Medicine 2022; 84: 104244.
[http://dx.doi.org/10.1101/2021.04.20.21255696]
[89]
Qu J, Lu SH, Lu ZL, Xu P, Xiang DX, Qu Q. Pharmacogenetic and case–control study on potassium channel related gene variants and genetic generalized epilepsy. Medicine (Baltimore) 2017; 96(26): e7321.
[http://dx.doi.org/10.1097/MD.0000000000007321] [PMID: 28658141]
[90]
Jorge BS, Campbell CM, Miller AR, et al. Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility. Proc Natl Acad Sci USA 2011; 108(13): 5443-8.
[http://dx.doi.org/10.1073/pnas.1017539108] [PMID: 21402906]
[91]
Rincon A, Paez-Rojas P, Suárez-Obando F. 8q22. 2q22. 3 Microdeletion Syndrome Associated with Hearing Loss and Intractable Epilepsy. Case Rep Genet 2019; 2019: 7608348.
[92]
Hao K, Niu T, Xu X, Fang Z, Xu X. Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness. Hum Genet 2005; 116(5): 378-83.
[http://dx.doi.org/10.1007/s00439-005-1256-5] [PMID: 15714333]
[93]
Wang Y, Peng J, Bai S, et al. A PIK3R2 mutation in familial temporal lobe epilepsy as a possible pathogenic variant. Front Genet 2021; 12: 596709.
[http://dx.doi.org/10.3389/fgene.2021.596709] [PMID: 34040629]
[94]
Mastrangelo M, Scheffer IE, Bramswig NC, et al. Epilepsy in KCNH1-related syndromes. Epileptic Disord 2016; 18(2): 123-36.
[http://dx.doi.org/10.1684/epd.2016.0830] [PMID: 27267311]
[95]
Fukai R, Saitsu H, Tsurusaki Y, et al. De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures. J Hum Genet 2016; 61(5): 381-7.
[http://dx.doi.org/10.1038/jhg.2016.1] [PMID: 26818738]
[96]
Yang Y, Vasylyev DV, Dib-Hajj F, et al. Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state. J Neurosci 2013; 33(42): 16586-93.
[http://dx.doi.org/10.1523/JNEUROSCI.2307-13.2013] [PMID: 24133262]
[97]
Bagnall RD, Crompton DE, Semsarian C. Genetic basis of sudden unexpected death in epilepsy. Front Neurol 2017; 8: 348.
[http://dx.doi.org/10.3389/fneur.2017.00348] [PMID: 28775708]
[98]
Partemi S, Cestèle S, Pezzella M, et al. Loss-of-function KCNH2 mutation in a family with long QT syndrome, epilepsy, and sudden death. Epilepsia 2013; 54(8): e112-6.
[http://dx.doi.org/10.1111/epi.12259] [PMID: 23899126]
[99]
Soh MS, Bagnall RD, Bennett MF, et al. Loss‐of‐function variants in K v 11.1 cardiac channels as a biomarker for SUDEP. Ann Clin Transl Neurol 2021; 8(7): 1422-32.
[http://dx.doi.org/10.1002/acn3.51381] [PMID: 34002542]
[100]
Zhang X, Bertaso F, Yoo JW, et al. Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy. Nat Neurosci 2010; 13(9): 1056-8.
[http://dx.doi.org/10.1038/nn.2610] [PMID: 20676103]
[101]
Neusch C, Weishaupt JH, Bähr M. Kir channels in the CNS: emerging new roles and implications for neurological diseases. Cell Tissue Res 2003; 311(2): 131-8.
[http://dx.doi.org/10.1007/s00441-002-0669-x] [PMID: 12596033]
[102]
Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 2010; 90(1): 291-366.
[http://dx.doi.org/10.1152/physrev.00021.2009] [PMID: 20086079]
[103]
Du W, Bautista JF, Yang H, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 2005; 37(7): 733-8.
[http://dx.doi.org/10.1038/ng1585] [PMID: 15937479]
[104]
Pattnaik BR, Asuma MP, Spott R, Pillers DAM. Genetic defects in the hotspot of inwardly rectifying K+ (Kir) channels and their metabolic consequences: A review. Mol Genet Metab 2012; 105(1): 64-72.
[http://dx.doi.org/10.1016/j.ymgme.2011.10.004] [PMID: 22079268]
[105]
Dai AI, Bay A, Gorucu S, Sivasli E, Bosnak M. KCNJ10 potassium ion channel single nucleotide polymorphism in pediatric patients with idiopathic generalized epilepsy. Neurol Psychiatry Brain Res 2011; 17(1): 32-5.
[http://dx.doi.org/10.1016/j.npbr.2011.02.008]
[106]
Dai AI, Akcali A, Koska S, Oztuzcu S, Cengiz B, Demiryürek AT. Contribution of KCNJ10 gene polymorphisms in childhood epilepsy. J Child Neurol 2015; 30(3): 296-300.
[http://dx.doi.org/10.1177/0883073814539560] [PMID: 25008907]
[107]
Sicca F, Imbrici P, D’Adamo MC, et al. Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1. Neurobiol Dis 2011; 43(1): 239-47.
[http://dx.doi.org/10.1016/j.nbd.2011.03.016] [PMID: 21458570]
[108]
Buono RJ, Lohoff FW, Sander T, et al. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 2004; 58(2-3): 175-83.
[http://dx.doi.org/10.1016/j.eplepsyres.2004.02.003] [PMID: 15120748]
[109]
Heuser K, Nagelhus EA, Taubøll E, et al. Variants of the genes encoding AQP4 and Kir4.1 are associated with subgroups of patients with temporal lobe epilepsy. Epilepsy Res 2010; 88(1): 55-64.
[http://dx.doi.org/10.1016/j.eplepsyres.2009.09.023] [PMID: 19864112]
[110]
Reichold M, Zdebik AA, Lieberer E, et al. KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function. Proc Natl Acad Sci 2010; 107(32): 14490-5.
[http://dx.doi.org/10.1073/pnas.1003072107] [PMID: 20651251]
[111]
Manis AD, Palygin O, Isaeva E, et al. Kcnj16 knockout produces audiogenic seizures in the Dahl salt-sensitive rat. JCI Insight 2021; 6(1): e143251.
[http://dx.doi.org/10.1172/jci.insight.143251] [PMID: 33232300]
[112]
Schlingmann KP, Renigunta A, Hoorn EJ, et al. Defects in KCNJ16 cause a novel tubulopathy with hypokalemia, salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. J Am Soc Nephrol 2021; 32(6): 1498-512.
[http://dx.doi.org/10.1681/ASN.2020111587] [PMID: 33811157]
[113]
Burgraff N, Pavolv T, Levchenko V, et al. Altered pH homeostasis and acoustic induced seizures associated with kcnj16 loss of function mutation The FASEB Journal 2017; 31(S1): 1072.7.
[114]
Lopatin AN, Makhina EN, Nichols CG. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature 1994; 372(6504): 366-9.
[http://dx.doi.org/10.1038/372366a0] [PMID: 7969496]
[115]
Ambrosini E, Sicca F, Brignone MS, et al. Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism–epilepsy phenotype. Hum Mol Genet 2014; 23(18): 4875-86.
[http://dx.doi.org/10.1093/hmg/ddu201] [PMID: 24794859]
[116]
Patil N, Cox DR, Bhat D, Faham M, Myers RM, Peterson AS. A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nat Genet 1995; 11(2): 126-9.
[http://dx.doi.org/10.1038/ng1095-126] [PMID: 7550338]
[117]
Slesinger PA, Patil N, Liao YJ, Jan YN, Jan LY, Cox DR. Functional effects of the mouse weaver mutation on G protein-gated inwardly rectifying K+ channels. Neuron 1996; 16(2): 321-31.
[http://dx.doi.org/10.1016/S0896-6273(00)80050-1] [PMID: 8789947]
[118]
Hallmann K, Durner M, Sander T, Steinlein OK. Mutation analysis of the inwardly rectifying K+ channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy. Am J Med Genet 2000; 96(1): 8-11.
[http://dx.doi.org/10.1002/(SICI)1096-8628(20000207)96:1<8:AID-AJMG3>3.0.CO;2-S] [PMID: 10686544]
[119]
Lucarini N, Verrotti A, Napolioni V, Bosco G, Curatolo P. Genetic polymorphisms and idiopathic generalized epilepsies. Pediatr Neurol 2007; 37(3): 157-64.
[http://dx.doi.org/10.1016/j.pediatrneurol.2007.06.001] [PMID: 17765802]
[120]
Köhling R, Wolfart J. Potassium channels in epilepsy. Cold Spring Harb Perspect Med 2016; 6(5): a022871.
[http://dx.doi.org/10.1101/cshperspect.a022871] [PMID: 27141079]
[121]
Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H. International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol Rev 2005; 57(4): 463-72.
[http://dx.doi.org/10.1124/pr.57.4.9] [PMID: 16382103]
[122]
Martire M, Barrese V, D’Amico M, et al. Pre-synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals. J Neurochem 2010; 115(2): 411-22.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06938.x] [PMID: 20681950]
[123]
Jin W, Sugaya A, Tsuda T, Ohguchi H, Sugaya E. Relationship between large conductance calcium-activated potassium channel and bursting activity. Brain Res 2000; 860(1-2): 21-8.
[http://dx.doi.org/10.1016/S0006-8993(00)01943-0] [PMID: 10727620]
[124]
Ermolinsky B, Arshadmansab MF, Pacheco Otalora LF, Zarei MM, Garrido-Sanabria ER. Deficit of Kcnma1 mRNA expression in the dentate gyrus of epileptic rats. Neuroreport 2008; 19(13): 1291-4.
[http://dx.doi.org/10.1097/WNR.0b013e3283094bb6] [PMID: 18695509]
[125]
Lee US, Cui J. β subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia. J Physiol 2009; 587(7): 1481-98.
[http://dx.doi.org/10.1113/jphysiol.2009.169243] [PMID: 19204046]
[126]
Alagoz M, Kherad N, Bozkurt S, Yuksel A. New mutations in KCNT2 gene causing early infantile epileptic encephalopathy type 57: Case study and literature review. Acta Biochim Pol 2020; 67(3): 431-4.
[http://dx.doi.org/10.18388/abp.2020_5364] [PMID: 32931186]
[127]
Gururaj S, Palmer EE, Sheehan GD, et al. A de novo mutation in the sodium-activated potassium channel KCNT2 alters ion selectivity and causes epileptic encephalopathy. Cell Rep 2017; 21(4): 926-33.
[http://dx.doi.org/10.1016/j.celrep.2017.09.088] [PMID: 29069600]
[128]
Inuzuka LM, Macedo-Souza LI, Della-Ripa B, et al. Additional observation of a de novo pathogenic variant in KCNT2 leading to epileptic encephalopathy with clinical features of frontal lobe epilepsy. Brain Dev 2020; 42(9): 691-5.
[http://dx.doi.org/10.1016/j.braindev.2020.05.003] [PMID: 32773162]
[129]
Ambrosino P, Soldovieri MV, Bast T, et al. De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy. Ann Neurol 2018; 83(6): 1198-204.
[http://dx.doi.org/10.1002/ana.25248] [PMID: 29740868]
[130]
Mao X, Bruneau N, Gao Q, et al. The epilepsy of infancy with migrating focal seizures: identification of de novo mutations of the KCNT2 gene that exert inhibitory effects on the corresponding heteromeric KNa1. 1/KNa1. 2 potassium channel. Front Cell Neurosci 2020; 14: 1.
[http://dx.doi.org/10.3389/fncel.2020.00001] [PMID: 32038177]
[131]
Barcia G, Fleming MR, Deligniere A, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet 2012; 44(11): 1255-9.
[http://dx.doi.org/10.1038/ng.2441] [PMID: 23086397]
[132]
Gong P, Jiao X, Yu D, Yang Z. Case report: Causative De novo variants of KCNT2 for developmental and epileptic encephalopathy. Front Genet 2021; 12: 649556.
[http://dx.doi.org/10.3389/fgene.2021.649556] [PMID: 34276763]
[133]
Tian Y, et al. Analysis of a family with inherited generalized epilepsy with febrile seizures plus caused by the KCNT2 mutation and literature review. Zhonghua Shiyong Erke Linchuang Zazhi 2021; 136-9.
[134]
Kim GE, Kronengold J, Barcia G, et al. Human slack potassium channel mutations increase positive cooperativity between individual channels. Cell Rep 2014; 9(5): 1661-72.
[http://dx.doi.org/10.1016/j.celrep.2014.11.015] [PMID: 25482562]
[135]
Møller RS, Heron SE, Larsen LHG, et al. Mutations in KCNT1 cause a spectrum of focal epilepsies. Epilepsia 2015; 56(9): e114-20.
[http://dx.doi.org/10.1111/epi.13071] [PMID: 26122718]
[136]
Ohba C, Kato M, Takahashi N, et al. De novoKCNT 1 mutations in early-onset epileptic encephalopathy. Epilepsia 2015; 56(9): e121-8.
[http://dx.doi.org/10.1111/epi.13072] [PMID: 26140313]
[137]
Rizzo F, Ambrosino P, Guacci A, et al. Characterization of two de novo KCNT1 mutations in children with malignant migrating partial seizures in infancy. Mol Cell Neurosci 2016; 72: 54-63.
[http://dx.doi.org/10.1016/j.mcn.2016.01.004] [PMID: 26784557]
[138]
Heron SE, Smith KR, Bahlo M, et al. Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 2012; 44(11): 1188-90.
[http://dx.doi.org/10.1038/ng.2440] [PMID: 23086396]
[139]
Cole BA, Clapcote SJ, Muench SP, Lippiat JD. Targeting KNa1.1 channels in KCNT1-associated epilepsy. Trends Pharmacol Sci 2021; 42(8): 700-13.
[http://dx.doi.org/10.1016/j.tips.2021.05.003] [PMID: 34074526]
[140]
Sørensen AT, Kokaia M. Novel approaches to epilepsy treatment. Epilepsia 2013; 54(1): 1-10.
[http://dx.doi.org/10.1111/epi.12000] [PMID: 23106744]
[141]
Ghosh S, Sinha JK, Khan T, et al. Pharmacological and therapeutic approaches in the treatment of epilepsy. Biomedicines 2021; 9(5): 470.
[http://dx.doi.org/10.3390/biomedicines9050470] [PMID: 33923061]
[142]
Bergey GK. Initial treatment of epilepsy: Special issues in treating the elderly. Neurology 2004; 63(10) (Suppl. 4): S40-8.
[http://dx.doi.org/10.1212/WNL.63.10_suppl_4.S40] [PMID: 15557550]
[143]
Waszkielewicz AM, Gunia A, Szkaradek N. Słoczyńska K, Krupińska S, Marona H. Ion channels as drug targets in central nervous system disorders. Curr Med Chem 2013; 20(10): 1241-85.
[http://dx.doi.org/10.2174/0929867311320100005] [PMID: 23409712]
[144]
Sancheti JS, Sathaye S. Voltage gated ion channels as therapeutic target for drug discovery. J Pharm Biosci 2013; 1: 76-88.
[145]
Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol 2000; 58(3): 591-600.
[http://dx.doi.org/10.1124/mol.58.3.591] [PMID: 10953053]
[146]
Cárdenas-Rodríguez N, Carmona-Aparicio L, Pérez-Lozano DL, Ortega-Cuellar D, Gómez-Manzo S, Ignacio-Mejía I. Genetic variations associated with pharmacoresistant epilepsy. (Review). Mol Med Rep 2020; 21(4): 1685-701.
[PMID: 32319641]
[147]
Ko A, Youn SE, Kim SH, et al. Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. Epilepsy Res 2018; 141: 48-55.
[http://dx.doi.org/10.1016/j.eplepsyres.2018.02.003] [PMID: 29455050]
[148]
Parrini E, Marini C, Mei D, et al. Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum Mutat 2017; 38(2): 216-25.
[http://dx.doi.org/10.1002/humu.23149] [PMID: 27864847]
[149]
Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J. Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy. Clin Genet 2017; 91(5): 717-24.
[http://dx.doi.org/10.1111/cge.12901] [PMID: 27779742]
[150]
Miao P, Peng J, Chen C, Gai N, Yin F. A novel mutation in KCNB1 gene in a child with neuropsychiatric comorbidities with both intellectual disability and epilepsy and review of literature Zhonghua Er Ke Za Zhi 2017; 55(2): 115-9.
[PMID: 28173649]
[151]
Guo Y, Yan KP, Qu Q, et al. Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies. PLoS One 2015; 10(4): e0124896.
[http://dx.doi.org/10.1371/journal.pone.0124896] [PMID: 25874548]
[152]
Martin HC, Kim GE, Pagnamenta AT, et al. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. Hum Mol Genet 2014; 23(12): 3200-11.
[http://dx.doi.org/10.1093/hmg/ddu030] [PMID: 24463883]
[153]
Serino D, Specchio N, Pontrelli G, Vigevano F, Fusco L. Video/EEG findings in a KCNQ2 epileptic encephalopathy: A case report and revision of literature data. Epileptic Disord 2013; 15(2): 158-65.
[http://dx.doi.org/10.1684/epd.2013.0578] [PMID: 23774309]
[154]
Zhang L, Wang Y. Gene therapy in epilepsy. Biomed Pharmacother 2021; 143: 112075.
[http://dx.doi.org/10.1016/j.biopha.2021.112075] [PMID: 34488082]
[155]
Wykes RC, Kullmann DM, Pavlov I, Magloire V. Optogenetic approaches to treat epilepsy. J Neurosci Methods 2016; 260: 215-20.
[http://dx.doi.org/10.1016/j.jneumeth.2015.06.004] [PMID: 26072246]
[156]
Krook-Magnuson E, Armstrong C, Oijala M, Soltesz I. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nat Commun 2013; 4(1): 1376.
[http://dx.doi.org/10.1038/ncomms2376] [PMID: 23340416]
[157]
Wess J, Nakajima K, Jain S. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci 2013; 34(7): 385-92.
[http://dx.doi.org/10.1016/j.tips.2013.04.006] [PMID: 23769625]
[158]
Duarte F, Déglon N. Genome editing for CNS disorders. Front Neurosci 2020; 14: 579062.
[http://dx.doi.org/10.3389/fnins.2020.579062] [PMID: 33192264]
[159]
Snowball A, Chabrol E, Wykes RC, et al. Epilepsy gene therapy using an engineered potassium channel. J Neurosci 2019; 39(16): 3159-69.
[http://dx.doi.org/10.1523/JNEUROSCI.1143-18.2019] [PMID: 30755487]
[160]
Han Z, Chen C, Christiansen A, et al. Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome. Sci Transl Med 2020; 12(558): eaaz6100.
[http://dx.doi.org/10.1126/scitranslmed.aaz6100] [PMID: 32848094]

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