Abstract
According to the World Health Organization (WHO), epilepsy is the 4th most prevalent neurological disorder after migraine, stroke, and Alzheimer’s disease. There are numerous types of epileptic syndrome that are reported in children; one of them is Dravet syndrome. It is a neurological disorder of infants’ outset during the first year of life. Dravet syndrome is a genetically determined syndrome and the most studied form of genetic epilepsy. Nearly 70-80% of its cases are due to genetic alterations in the SCN1A gene, and almost 16% of cases are due to variations in the PCDH19 gene. Besides that, mutations in SCN1B, SCN2A, and GABRG2, including some novel genes, STXBP1, HCN1, and CDH2 have been observed in DS patients. It is a drug-resistant epileptic syndrome and its complete removal is still challenging. So, novel therapeutic techniques are being used to treat drug-resistant seizures. Recently, new strategies have been made to improve the neuron-specific targeting of AEDs encapsulated by nanocarriers. The nanocarriers will have a major contribution to nano-neuro medicines such as drug delivery, neuroimaging, neuroprotection, neurosurgery, and neuroregeneration. The nanotechnology-mediated techniques also have a fantastic success rate in gene therapy, as reported in recent years. The anti- epileptic drug delivery with the help of nanoparticles, at the targeted position, makes them applicable for the possible treatment of drug-resistant seizures and gives new hope to patients affected with it.
Keywords: Epilepsy, Dravet syndrome (DS), genetics, drug-resistant, treatment, nanoparticles
Graphical Abstract
[http://dx.doi.org/10.1016/S0140-6736(12)61381-6] [PMID: 23021288]
[http://dx.doi.org/10.1155/2019/5270503]
[http://dx.doi.org/10.3126/egn.v2i2.29244]
[http://dx.doi.org/10.1111/epi.16054] [PMID: 31904125]
[http://dx.doi.org/10.4103/aian.AIAN_447_16] [PMID: 28615892]
[http://dx.doi.org/10.1097/NRL.0b013e31815bb07d] [PMID: 18090951]
[http://dx.doi.org/10.1016/j.bandl.2017.12.005] [PMID: 29610055]
[http://dx.doi.org/10.1111/j.1528-1167.2011.03041.x] [PMID: 21449936]
[http://dx.doi.org/10.1523/JNEUROSCI.4139-03.2004] [PMID: 15102918]
[http://dx.doi.org/10.1038/nn1754] [PMID: 16921370]
[http://dx.doi.org/10.1038/s41598-019-42191-0] [PMID: 30996233]
[http://dx.doi.org/10.1172/JCI66220] [PMID: 23524966]
[http://dx.doi.org/10.1111/j.1528-1167.2011.02994.x] [PMID: 21463272]
[http://dx.doi.org/10.1016/j.ajhg.2013.09.017] [PMID: 24207121]
[http://dx.doi.org/10.1136/jmg.2009.074328] [PMID: 20522430]
[PMID: 31497436]
[http://dx.doi.org/10.1093/brain/120.3.479] [PMID: 9126059]
[http://dx.doi.org/10.1111/epi.13889] [PMID: 28880996]
[http://dx.doi.org/10.1212/WNL.0000000000003868] [PMID: 28356460]
[http://dx.doi.org/10.1038/s41598-017-01851-9] [PMID: 28490751]
[http://dx.doi.org/10.1186/s13073-016-0278-z] [PMID: 26917491]
[http://dx.doi.org/10.1523/JNEUROSCI.3901-08.2008] [PMID: 19005038]
[http://dx.doi.org/10.1016/B978-0-12-813146-6.00029-1]
[http://dx.doi.org/10.1111/j.1528-1167.2006.00688.x] [PMID: 17105460]
[http://dx.doi.org/10.1016/j.pediatrneurol.2017.01.004] [PMID: 28233668]
[http://dx.doi.org/10.1111/j.1528-1167.2007.01122.x] [PMID: 17561957]
[http://dx.doi.org/10.1056/NEJMoa1611618] [PMID: 28538134]
[http://dx.doi.org/10.1016/j.yebeh.2017.05.037] [PMID: 28683344]
[http://dx.doi.org/10.3389/fneur.2017.00301] [PMID: 28729850]
[http://dx.doi.org/10.1586/14737175.3.1.127] [PMID: 19810855]
[http://dx.doi.org/10.1159/000222775] [PMID: 19521080]
[http://dx.doi.org/10.1002/glia.22311] [PMID: 22378298]
[http://dx.doi.org/10.1208/s12248-017-0096-2] [PMID: 28550637]
[http://dx.doi.org/10.1124/jpet.301.1.7] [PMID: 11907151]
[http://dx.doi.org/10.1038/ncpneuro0521] [PMID: 17549058]
[http://dx.doi.org/10.1002/14651858.CD011501.pub2]
[http://dx.doi.org/10.1001/jamaneurol.2019.1464] [PMID: 31180505]
[http://dx.doi.org/10.1007/s13760-019-01120-8] [PMID: 30868468]
[http://dx.doi.org/10.2174/1389557516666161013105000] [PMID: 27739360]
[http://dx.doi.org/10.3390/pharmaceutics11030118] [PMID: 30871237]
[http://dx.doi.org/10.1016/j.ajhg.2018.10.023] [PMID: 30526861]
[http://dx.doi.org/10.1002/ccr3.787] [PMID: 28469861]
[http://dx.doi.org/10.1002/humu.10217] [PMID: 12754708]
[http://dx.doi.org/10.1111/j.1528-1167.2011.02997.x] [PMID: 21463275]
[http://dx.doi.org/10.1177/2329048X17706794]
[PMID: 28012175]
[http://dx.doi.org/10.1016/j.clineuro.2016.05.008] [PMID: 27209029]
[http://dx.doi.org/10.1186/s12881-016-0294-2] [PMID: 27113213]
[http://dx.doi.org/10.1212/WNL.0000000000000291] [PMID: 24623842]
[http://dx.doi.org/10.1038/ng.150] [PMID: 18469812]
[http://dx.doi.org/10.1212/WNL.0000000000002457] [PMID: 26865513]
[http://dx.doi.org/10.1016/S0092-8674(00)81434-8] [PMID: 9630217]
[http://dx.doi.org/10.1038/ng.2952] [PMID: 24747641]
[http://dx.doi.org/10.1038/ng.2646] [PMID: 23708187]
[http://dx.doi.org/10.1016/j.seizure.2019.01.025] [PMID: 30776697]
[http://dx.doi.org/10.1371/journal.pgen.1000381] [PMID: 19214208]
[http://dx.doi.org/10.1001/jamaneurol.2016.0449] [PMID: 27367160]
[http://dx.doi.org/10.1523/JNEUROSCI.2475-09.2009] [PMID: 19710327]
[http://dx.doi.org/10.1016/j.braindev.2009.08.009] [PMID: 19783390]
[http://dx.doi.org/10.1111/epi.12323] [PMID: 23895530]
[http://dx.doi.org/10.1016/j.nbd.2008.07.017] [PMID: 18755274]
[http://dx.doi.org/10.1097/MD.0000000000014974] [PMID: 30921204]
[http://dx.doi.org/10.1212/WNL.0000000000001211] [PMID: 25568300]
[http://dx.doi.org/10.1111/jnc.15120] [PMID: 32643187]
[http://dx.doi.org/10.1016/j.yebeh.2015.06.029] [PMID: 26262932]
[http://dx.doi.org/10.1101/cshperspect.a028043] [PMID: 27371672]
[http://dx.doi.org/10.1016/j.yebeh.2009.02.036] [PMID: 19341977]
[http://dx.doi.org/10.1016/B978-0-12-804066-9.00066-3]
[http://dx.doi.org/10.1016/j.drudis.2016.06.004] [PMID: 27312874]
[http://dx.doi.org/10.1016/j.biomaterials.2015.09.041] [PMID: 26447556]
[http://dx.doi.org/10.2217/pgs.10.126] [PMID: 21047204]
[http://dx.doi.org/10.1016/j.yebeh.2019.07.031] [PMID: 31378558]
[http://dx.doi.org/10.1016/j.phrs.2019.04.031] [PMID: 31051235]
[http://dx.doi.org/10.1016/j.lfs.2020.118081] [PMID: 32663576]
[http://dx.doi.org/10.1016/j.pharmthera.2019.05.010] [PMID: 31128154]
[http://dx.doi.org/10.12688/f1000research.8214.1] [PMID: 27239287]
[http://dx.doi.org/10.1080/09647049209525522] [PMID: 11618419]
[http://dx.doi.org/10.1111/j.1365-2885.1985.tb00934.x] [PMID: 4020942]
[http://dx.doi.org/10.1111/j.1600-051X.1982.tb02109.x] [PMID: 6816838]
[http://dx.doi.org/10.1136/pgmj.54.638.796]
[http://dx.doi.org/10.1007/978-3-642-85921-2_7]
[http://dx.doi.org/10.1111/j.1469-8749.1995.tb15014.x] [PMID: 7672465]
[http://dx.doi.org/10.1111/j.1600-0404.1976.tb04797.x] [PMID: 822682]
[http://dx.doi.org/10.1111/j.1469-8749.1977.tb08368.x] [PMID: 407118]
[http://dx.doi.org/10.1212/WNL.36.2.217] [PMID: 3511402]
[http://dx.doi.org/10.1136/jnnp.53.11.1008] [PMID: 2283513]
[http://dx.doi.org/10.1016/S0387-7604(99)00023-6] [PMID: 10413016]
[http://dx.doi.org/10.1111/j.1600-0404.1992.tb04038.x] [PMID: 1585795]
[http://dx.doi.org/10.1179/016164101101199414] [PMID: 11760873]
[http://dx.doi.org/10.1017/S031716710003482X] [PMID: 9706732]
[http://dx.doi.org/10.1016/S0920-1211(96)00084-8] [PMID: 8956929]
[http://dx.doi.org/10.1517/13543784.9.7.1611] [PMID: 11060765]
[http://dx.doi.org/10.1517/14656566.1.6.1245] [PMID: 11249491]
[http://dx.doi.org/10.1007/s40265-019-01204-y] [PMID: 31617141]
[http://dx.doi.org/10.1016/j.seizure.2009.01.001] [PMID: 19213577]
[http://dx.doi.org/10.1517/14656566.8.12.1931] [PMID: 17696794]
[http://dx.doi.org/10.1016/j.eplepsyres.2007.03.004] [PMID: 17433624]
[http://dx.doi.org/10.1517/13543780802635107] [PMID: 19236268]
[http://dx.doi.org/10.1038/nrd3561] [PMID: 21959281]
[http://dx.doi.org/10.1016/j.neuint.2012.02.035] [PMID: 22433907]
[http://dx.doi.org/10.1007/s40263-013-0129-z] [PMID: 24357084]
[http://dx.doi.org/10.1186/s13023-016-0530-z] [PMID: 27809914]
[http://dx.doi.org/10.1016/j.yebeh.2018.11.032] [PMID: 30530134]
[http://dx.doi.org/10.5694/mja18.00023] [PMID: 30092753]
[http://dx.doi.org/10.1038/nbt.3199] [PMID: 25849900]
[http://dx.doi.org/10.1038/s41593-017-0060-6] [PMID: 29335603]
[http://dx.doi.org/10.1016/j.nbd.2020.104954] [PMID: 32445790]
[http://dx.doi.org/10.1016/j.ymthe.2019.08.018] [PMID: 31607539]
[http://dx.doi.org/10.1038/nature09160] [PMID: 20543823]
[http://dx.doi.org/10.1089/hum.2019.225] [PMID: 31830809]
[http://dx.doi.org/10.1089/hum.2019.012] [PMID: 31017018]
[http://dx.doi.org/10.1371/journal.pbio.1001944] [PMID: 25203314]
[PMID: 32001838]
[http://dx.doi.org/10.1126/scitranslmed.aaz6100] [PMID: 32848094]
[http://dx.doi.org/10.1002/ana.25676] [PMID: 31943325]
[http://dx.doi.org/10.1038/mt.2009.255] [PMID: 19904234]
[http://dx.doi.org/10.1089/104303401753153947] [PMID: 11589831]
[http://dx.doi.org/10.1089/crispr.2020.0025] [PMID: 32833535]
[http://dx.doi.org/10.1126/science.aav9023] [PMID: 31000663]
[http://dx.doi.org/10.1038/nmeth.3284] [PMID: 25664545]
[http://dx.doi.org/10.1038/nmeth.4278] [PMID: 28459458]
[http://dx.doi.org/10.1002/jimd.12251] [PMID: 32391605]
[http://dx.doi.org/10.1038/gt.2017.41] [PMID: 28504657]
[http://dx.doi.org/10.1080/10717544.2016.1177136] [PMID: 27145899]
[http://dx.doi.org/10.1038/s41591-019-0344-3] [PMID: 30778238]
[http://dx.doi.org/10.1002/adfm.201703036] [PMID: 29755309]
[http://dx.doi.org/10.1021/acs.chemrev.6b00799] [PMID: 28640612]
[http://dx.doi.org/10.1016/j.ccr.2018.07.001]
[http://dx.doi.org/10.1016/j.colsurfb.2018.01.031] [PMID: 29413593]
[http://dx.doi.org/10.1089/nat.2018.0721] [PMID: 29683383]
[http://dx.doi.org/10.1038/s41582-020-00419-y] [PMID: 33024326]
[http://dx.doi.org/10.1212/WNL.63.10_suppl_4.S3] [PMID: 15557548]
[http://dx.doi.org/10.1177/0885328211429495] [PMID: 22207601]
[http://dx.doi.org/10.2217/nnm-2020-0088] [PMID: 32618490]
[http://dx.doi.org/10.1016/j.nurt.2009.01.018] [PMID: 19332327]
[http://dx.doi.org/10.1016/j.drudis.2015.06.008] [PMID: 26103617]
[http://dx.doi.org/10.2217/nnm.14.27] [PMID: 24827845]
[http://dx.doi.org/10.1016/j.addr.2011.11.014] [PMID: 22178615]
[http://dx.doi.org/10.1016/j.cej.2018.03.176]
[http://dx.doi.org/10.1016/j.ijpharm.2018.05.023] [PMID: 29751140]
[http://dx.doi.org/10.2217/nnm.15.173] [PMID: 26649451]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.09.073] [PMID: 28939512]
[http://dx.doi.org/10.1007/s40263-016-0405-9] [PMID: 28101766]
[http://dx.doi.org/10.1016/j.apsb.2016.05.013] [PMID: 27471668]
[http://dx.doi.org/10.1155/2016/2412958]
[http://dx.doi.org/10.1016/B978-0-12-816913-1.00012-X]
[http://dx.doi.org/10.1016/j.nano.2016.01.018] [PMID: 26964483]
[PMID: 31790722]
[http://dx.doi.org/10.3171/2014.12.FOCUS14758] [PMID: 25727231]
[http://dx.doi.org/10.1021/mp200469a] [PMID: 22047066]
[http://dx.doi.org/10.1016/j.colsurfb.2018.03.052] [PMID: 29627680]
[http://dx.doi.org/10.2174/1389200215666141125142605] [PMID: 25429676]
[http://dx.doi.org/10.1369/jhc.2008.950659] [PMID: 18319271]
[http://dx.doi.org/10.1038/nnano.2012.237] [PMID: 23334168]
[http://dx.doi.org/10.1039/c2nr31263h] [PMID: 22961067]
[http://dx.doi.org/10.1016/j.nantod.2010.05.003]
[http://dx.doi.org/10.2147/OTT.S120662] [PMID: 28123308]
[http://dx.doi.org/10.5698/1535-7511-12.5.199] [PMID: 23118608]
[http://dx.doi.org/10.1080/10717544.2016.1223216] [PMID: 27648847]
[http://dx.doi.org/10.1016/j.nano.2018.01.019] [PMID: 29454994]
[http://dx.doi.org/10.12659/MSM.915025] [PMID: 30843525]
[http://dx.doi.org/10.1159/000497361] [PMID: 34676332]
[http://dx.doi.org/10.3390/ph13090219] [PMID: 32872355]
[http://dx.doi.org/10.1021/acsami.0c13372] [PMID: 32809788]
[http://dx.doi.org/10.37358/MP.20.1.5331]
[http://dx.doi.org/10.1016/j.ejpb.2020.06.003] [PMID: 32531424]
[http://dx.doi.org/10.2147/DDDT.S263898] [PMID: 33116420]
[http://dx.doi.org/10.34172/apb.2021.016] [PMID: 33747862]
[PMID: 25044856]
[http://dx.doi.org/10.1016/j.brainres.2009.09.039] [PMID: 19766611]
[PMID: 32921169]
[http://dx.doi.org/10.1016/j.jddst.2016.04.003]
[http://dx.doi.org/10.1166/jnn.2016.12431] [PMID: 27483926]
[http://dx.doi.org/10.1208/s12249-015-0294-0] [PMID: 25698083]
[http://dx.doi.org/10.1016/j.ejps.2018.01.028] [PMID: 29341900]
[http://dx.doi.org/10.1016/j.ejpb.2018.11.002] [PMID: 30399400]
[PMID: 25792832]
[http://dx.doi.org/10.1007/s12247-018-9343-z]
[http://dx.doi.org/10.1002/jps.21924] [PMID: 19877171]
[http://dx.doi.org/10.2174/2405461503666180413160954]
[http://dx.doi.org/10.4155/tde-2018-0022] [PMID: 30071804]
[http://dx.doi.org/10.3390/ijms21020591] [PMID: 31963328]
[http://dx.doi.org/10.1124/mi.10.5.6] [PMID: 21045243]
[PMID: 12935438]
[http://dx.doi.org/10.1002/0470846356.ch4]
[http://dx.doi.org/10.1016/S0920-1211(98)00106-5] [PMID: 10210025]
[http://dx.doi.org/10.1002/admi.202101391]
[http://dx.doi.org/10.4238/gmr15048752] [PMID: 27886333]
[http://dx.doi.org/10.3390/mi10060375] [PMID: 31195652]
[http://dx.doi.org/10.1016/j.jare.2018.06.005] [PMID: 30581608]
[http://dx.doi.org/10.3390/pharmaceutics11030101] [PMID: 30813646]
[http://dx.doi.org/10.1002/adfm.201700489] [PMID: 30853878]
[http://dx.doi.org/10.15171/apb.2016.044] [PMID: 27766216]
[http://dx.doi.org/10.1002/adfm.202003054]
[http://dx.doi.org/10.2217/nnm-2019-0443] [PMID: 32370600]
[http://dx.doi.org/10.1007/978-3-319-99602-8_10]
[http://dx.doi.org/10.15171/bi.2018.08] [PMID: 29713603]
[http://dx.doi.org/10.2174/2210681208666180125143953]