CA2612180A1 - Methods of treatment, and diagnosis of epilepsy by detecting mutations in the scn1a gene - Google Patents
Methods of treatment, and diagnosis of epilepsy by detecting mutations in the scn1a gene Download PDFInfo
- Publication number
- CA2612180A1 CA2612180A1 CA002612180A CA2612180A CA2612180A1 CA 2612180 A1 CA2612180 A1 CA 2612180A1 CA 002612180 A CA002612180 A CA 002612180A CA 2612180 A CA2612180 A CA 2612180A CA 2612180 A1 CA2612180 A1 CA 2612180A1
- Authority
- CA
- Canada
- Prior art keywords
- smei
- alteration
- scn1a
- epilepsy
- related syndrome
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 106
- 206010015037 epilepsy Diseases 0.000 title claims abstract description 92
- 238000003745 diagnosis Methods 0.000 title claims abstract description 31
- 230000035772 mutation Effects 0.000 title claims description 66
- 238000011282 treatment Methods 0.000 title claims description 21
- 108090000623 proteins and genes Proteins 0.000 title description 78
- 101000631760 Homo sapiens Sodium channel protein type 1 subunit alpha Proteins 0.000 claims abstract description 279
- 201000007547 Dravet syndrome Diseases 0.000 claims abstract description 246
- 102100028910 Sodium channel protein type 1 subunit alpha Human genes 0.000 claims abstract description 223
- 230000004075 alteration Effects 0.000 claims abstract description 140
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 108
- 238000012360 testing method Methods 0.000 claims abstract description 30
- 208000002877 Epileptic Syndromes Diseases 0.000 claims abstract description 17
- 208000024658 Epilepsy syndrome Diseases 0.000 claims abstract description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 89
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 81
- 229920001184 polypeptide Polymers 0.000 claims description 72
- 238000003556 assay Methods 0.000 claims description 60
- 150000007523 nucleic acids Chemical class 0.000 claims description 52
- 102000039446 nucleic acids Human genes 0.000 claims description 51
- 108020004707 nucleic acids Proteins 0.000 claims description 51
- 108010052164 Sodium Channels Proteins 0.000 claims description 48
- 102000018674 Sodium Channels Human genes 0.000 claims description 47
- 108020004414 DNA Proteins 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 33
- 239000012634 fragment Substances 0.000 claims description 29
- 239000000523 sample Substances 0.000 claims description 19
- 206010061334 Partial seizures Diseases 0.000 claims description 17
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 claims description 16
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 108020004999 messenger RNA Proteins 0.000 claims description 15
- 239000000556 agonist Substances 0.000 claims description 14
- 239000005557 antagonist Substances 0.000 claims description 14
- 230000000295 complement effect Effects 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 238000012216 screening Methods 0.000 claims description 14
- 238000001712 DNA sequencing Methods 0.000 claims description 13
- 239000002773 nucleotide Substances 0.000 claims description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 12
- 239000013604 expression vector Substances 0.000 claims description 12
- 201000007186 focal epilepsy Diseases 0.000 claims description 12
- 201000001993 idiopathic generalized epilepsy Diseases 0.000 claims description 12
- 125000003729 nucleotide group Chemical group 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 208000037158 Partial Epilepsies Diseases 0.000 claims description 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 11
- 230000002068 genetic effect Effects 0.000 claims description 11
- 239000013610 patient sample Substances 0.000 claims description 11
- 241000699670 Mus sp. Species 0.000 claims description 10
- 230000000692 anti-sense effect Effects 0.000 claims description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 4
- 241000700159 Rattus Species 0.000 claims description 4
- 241000282472 Canis lupus familiaris Species 0.000 claims description 3
- 241000283707 Capra Species 0.000 claims description 3
- 241000282693 Cercopithecidae Species 0.000 claims description 3
- 102000053602 DNA Human genes 0.000 claims description 3
- 241000282326 Felis catus Species 0.000 claims description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 3
- 238000002255 vaccination Methods 0.000 claims description 3
- 241000700198 Cavia Species 0.000 claims description 2
- 241000699800 Cricetinae Species 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 241000282579 Pan Species 0.000 claims description 2
- 241001494479 Pecora Species 0.000 claims description 2
- 241000282887 Suidae Species 0.000 claims description 2
- 230000002411 adverse Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 238000003306 harvesting Methods 0.000 claims description 2
- 101000829171 Hypocrea virens (strain Gv29-8 / FGSC 10586) Effector TSP1 Proteins 0.000 claims 3
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 172
- 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 description 165
- 206010010904 Convulsion Diseases 0.000 description 64
- 210000004027 cell Anatomy 0.000 description 40
- 102000004169 proteins and genes Human genes 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 34
- 238000004458 analytical method Methods 0.000 description 33
- 238000003752 polymerase chain reaction Methods 0.000 description 31
- 108091093088 Amplicon Proteins 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 230000014509 gene expression Effects 0.000 description 16
- 238000013459 approach Methods 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 108700024394 Exon Proteins 0.000 description 14
- 230000001037 epileptic effect Effects 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 239000000499 gel Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 208000014644 Brain disease Diseases 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 208000032274 Encephalopathy Diseases 0.000 description 11
- 108091033319 polynucleotide Proteins 0.000 description 11
- 102000040430 polynucleotide Human genes 0.000 description 11
- 239000002157 polynucleotide Substances 0.000 description 11
- 108091006146 Channels Proteins 0.000 description 10
- 238000000537 electroencephalography Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 230000027455 binding Effects 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 201000008186 generalized epilepsy with febrile seizures plus Diseases 0.000 description 9
- 208000002091 Febrile Seizures Diseases 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 238000012163 sequencing technique Methods 0.000 description 8
- 108091026890 Coding region Proteins 0.000 description 7
- 208000003078 Generalized Epilepsy Diseases 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 101150036876 cre gene Proteins 0.000 description 7
- 230000001351 cycling effect Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000007877 drug screening Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 238000011835 investigation Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000036961 partial effect Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 206010071081 Idiopathic generalised epilepsy Diseases 0.000 description 6
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 238000010363 gene targeting Methods 0.000 description 6
- 238000003018 immunoassay Methods 0.000 description 6
- 210000000287 oocyte Anatomy 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 238000012408 PCR amplification Methods 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000002493 microarray Methods 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- 208000034308 Grand mal convulsion Diseases 0.000 description 4
- 101000684813 Homo sapiens Sodium channel subunit beta-1 Proteins 0.000 description 4
- 201000006347 Intellectual Disability Diseases 0.000 description 4
- 208000037004 Myoclonic-astatic epilepsy Diseases 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 206010037660 Pyrexia Diseases 0.000 description 4
- 102000006382 Ribonucleases Human genes 0.000 description 4
- 108010083644 Ribonucleases Proteins 0.000 description 4
- 102100023732 Sodium channel subunit beta-1 Human genes 0.000 description 4
- 238000000137 annealing Methods 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000009510 drug design Methods 0.000 description 4
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000007823 electrophoretic assay Methods 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000011813 knockout mouse model Methods 0.000 description 4
- 229960001848 lamotrigine Drugs 0.000 description 4
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000007479 molecular analysis Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 206010003628 Atonic seizures Diseases 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010018101 Generalised tonic-clonic seizures Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108091027305 Heteroduplex Proteins 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 3
- 108090000862 Ion Channels Proteins 0.000 description 3
- 208000002033 Myoclonus Diseases 0.000 description 3
- 108010038807 Oligopeptides Proteins 0.000 description 3
- 102000015636 Oligopeptides Human genes 0.000 description 3
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 3
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 3
- 108010001441 Phosphopeptides Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 108010006785 Taq Polymerase Proteins 0.000 description 3
- 206010043994 Tonic convulsion Diseases 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 208000028311 absence seizure Diseases 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 206010016284 febrile convulsion Diseases 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 102000054765 polymorphisms of proteins Human genes 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000002805 secondary assay Methods 0.000 description 3
- 208000005809 status epilepticus Diseases 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010021750 Infantile Spasms Diseases 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 201000006791 West syndrome Diseases 0.000 description 2
- 208000003554 absence epilepsy Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000012875 competitive assay Methods 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000003935 denaturing gradient gel electrophoresis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000001787 epileptiform Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 150000002484 inorganic compounds Chemical class 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000002151 myoclonic effect Effects 0.000 description 2
- 238000002610 neuroimaging Methods 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000002424 x-ray crystallography Methods 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- YUDPTGPSBJVHCN-DZQJYWQESA-N 4-methylumbelliferyl beta-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-DZQJYWQESA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000002333 Asphyxia Neonatorum Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 201000001913 Childhood absence epilepsy Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000011724 DNA Repair Enzymes Human genes 0.000 description 1
- 108010076525 DNA Repair Enzymes Proteins 0.000 description 1
- 108091027757 Deoxyribozyme Proteins 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 108700003861 Dominant Genes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241001203952 Feia Species 0.000 description 1
- 102000017934 GABA-B receptor Human genes 0.000 description 1
- 108060003377 GABA-B receptor Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 230000010558 Gene Alterations Effects 0.000 description 1
- PDLGMYVCPJOYAR-DKIMLUQUSA-N Glu-Leu-Phe-Ala Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 PDLGMYVCPJOYAR-DKIMLUQUSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000684826 Homo sapiens Sodium channel protein type 2 subunit alpha Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000035899 Infantile spasms syndrome Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 201000008189 Juvenile absence epilepsy Diseases 0.000 description 1
- 206010071082 Juvenile myoclonic epilepsy Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001327631 Meara Species 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 101100293261 Mus musculus Naa15 gene Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 108010038272 MutS Proteins Proteins 0.000 description 1
- 101150082943 NAT1 gene Proteins 0.000 description 1
- 206010028923 Neonatal asphyxia Diseases 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- -1 Nucleotide Amino Acid Chemical class 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 101710172814 Sodium channel protein Proteins 0.000 description 1
- 102220524755 Sodium channel protein type 1 subunit alpha_D674G_mutation Human genes 0.000 description 1
- 102220478467 Sodium channel protein type 1 subunit alpha_F1543S_mutation Human genes 0.000 description 1
- 102220525586 Sodium channel protein type 1 subunit alpha_F945L_mutation Human genes 0.000 description 1
- 102220525726 Sodium channel protein type 1 subunit alpha_G950E_mutation Human genes 0.000 description 1
- 102220524777 Sodium channel protein type 1 subunit alpha_L783P_mutation Human genes 0.000 description 1
- 102220525683 Sodium channel protein type 1 subunit alpha_M973V_mutation Human genes 0.000 description 1
- 102220478479 Sodium channel protein type 1 subunit alpha_R1596C_mutation Human genes 0.000 description 1
- 102220547055 Sodium channel protein type 1 subunit alpha_R1657H_mutation Human genes 0.000 description 1
- 102220547008 Sodium channel protein type 1 subunit alpha_T1721R_mutation Human genes 0.000 description 1
- 102220525601 Sodium channel protein type 1 subunit alpha_V944E_mutation Human genes 0.000 description 1
- 102220547009 Sodium channel protein type 1 subunit alpha_W1726R_mutation Human genes 0.000 description 1
- 102100023150 Sodium channel protein type 2 subunit alpha Human genes 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000000367 ab initio method Methods 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 208000026802 afebrile Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003467 cheek Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 108010041758 cleavase Proteins 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 231100001129 embryonic lethality Toxicity 0.000 description 1
- 108010064144 endodeoxyribonuclease VII Proteins 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000003167 genetic complementation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 208000034287 idiopathic generalized susceptibility to 7 epilepsy Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000002109 interictal effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012917 library technology Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 238000012402 patch clamp technique Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000003793 prenatal diagnosis Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 201000001204 progressive myoclonus epilepsy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000000455 protein structure prediction Methods 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000003906 pulsed field gel electrophoresis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 102200072408 rs121917982 Human genes 0.000 description 1
- 102200072320 rs121917985 Human genes 0.000 description 1
- 102200073167 rs121917990 Human genes 0.000 description 1
- 102200072297 rs121918767 Human genes 0.000 description 1
- 102220067043 rs201079458 Human genes 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 230000037322 slow-wave sleep Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
- 229960001918 tiagabine Drugs 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940102566 valproate Drugs 0.000 description 1
- 229960005318 vigabatrin Drugs 0.000 description 1
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2857—Seizure disorders; Epilepsy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2005903146 | 2005-06-16 | ||
| AU2005903146A AU2005903146A0 (en) | 2005-06-16 | Methods for the diagnosis and treatment of epilepsy | |
| PCT/AU2006/000841 WO2006133508A1 (en) | 2005-06-16 | 2006-06-16 | Methods of treatment, and diagnosis of epilepsy by detecting mutations in the scn1a gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2612180A1 true CA2612180A1 (en) | 2006-12-21 |
Family
ID=37531886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002612180A Abandoned CA2612180A1 (en) | 2005-06-16 | 2006-06-16 | Methods of treatment, and diagnosis of epilepsy by detecting mutations in the scn1a gene |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20100088778A1 (https=) |
| EP (1) | EP1904630A4 (https=) |
| JP (1) | JP2008546376A (https=) |
| CA (1) | CA2612180A1 (https=) |
| NZ (1) | NZ564892A (https=) |
| WO (1) | WO2006133508A1 (https=) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005501536A (ja) * | 2001-07-18 | 2005-01-20 | バイオノミックス リミテッド | イオンチャネルにおける変異 |
| AU2003904154A0 (en) | 2003-08-07 | 2003-08-21 | Bionomics Limited | Mutations in ion channels |
| AU2003901425A0 (en) * | 2003-03-27 | 2003-04-10 | Bionomics Limited | A diagnostic method for epilepsy |
| JP5540343B2 (ja) * | 2007-11-06 | 2014-07-02 | 国立大学法人 岡山大学 | 小児てんかん患者における急性脳炎または急性脳症の罹患リスク判定データの取得方法およびその利用 |
| JP5608863B2 (ja) * | 2007-12-28 | 2014-10-15 | 公立大学法人横浜市立大学 | 新生児期〜乳児期発症の難治性てんかんの検出方法 |
| EP2467404B1 (en) | 2009-08-20 | 2015-09-30 | Biosceptre International Limited | Anti p2x7 receptor antibodies and fragments thereof |
| US20130036482A1 (en) | 2010-01-29 | 2013-02-07 | National University Corporation Okayama University | Method for assessment of potential for development of dravet syndrome and use thereof |
| JP2011188837A (ja) * | 2010-03-16 | 2011-09-29 | Hirosaki Univ | リーシークエンスｄｎａチップおよび最適抗てんかん薬決定方法 |
| CN109112126B (zh) * | 2010-06-23 | 2024-06-14 | 库尔纳公司 | 通过抑制电压门控钠通道α亚基(SCNA)的天然反义转录物而治疗SCNA相关疾病 |
| TWI734935B (zh) * | 2011-06-24 | 2021-08-01 | 美商可娜公司 | 上調電壓門控鈉離子通道第Ｉ型α次單元(ＳＣＮ１Ａ)之表現及/或功能之反義寡核苷酸及其用途 |
| US9549909B2 (en) | 2013-05-03 | 2017-01-24 | The Katholieke Universiteit Leuven | Method for the treatment of dravet syndrome |
| CN107111673B (zh) | 2014-09-29 | 2021-03-23 | 周格尼克斯国际有限公司 | 控制药物分配的控制系统 |
| JP2018531975A (ja) | 2015-10-30 | 2018-11-01 | ピーティーシー セラピューティクス，インコーポレーテッド | てんかんの治療方法 |
| WO2017106377A1 (en) * | 2015-12-14 | 2017-06-22 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of autosomal dominant mental retardation-5 and dravet syndrome |
| WO2017112701A1 (en) | 2015-12-22 | 2017-06-29 | Zogenix International Limited | Metabolism resistant fenfluramine analogs and methods of using the same |
| ES3024232T3 (en) | 2015-12-22 | 2025-06-04 | Zogenix International Ltd | Fenfluramine compositions and methods of preparing the same |
| SG11201900975XA (en) | 2016-08-24 | 2019-03-28 | Zogenix International Ltd | Formulation for inhibiting formation of 5-ht 2b agonists and methods of using same |
| WO2018098491A1 (en) | 2016-11-28 | 2018-05-31 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| DK3548033T3 (da) | 2016-11-28 | 2024-07-15 | Praxis Prec Medicines Inc | Forbindelser og deres fremgangsmåde til anvendelse |
| WO2018098500A1 (en) * | 2016-11-28 | 2018-05-31 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| CN106719436A (zh) * | 2016-12-20 | 2017-05-31 | 郑州伊美诺生物技术有限公司 | 一种制备单克隆抗体的小鼠模型建立方法 |
| US11492345B2 (en) | 2017-02-13 | 2022-11-08 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| WO2018187480A1 (en) | 2017-04-04 | 2018-10-11 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| US20200085838A1 (en) * | 2017-05-16 | 2020-03-19 | Praxis Precision Medicines, Inc. | Methods of treating epilepsy and neurodevelopmental disorders |
| US11278535B2 (en) | 2017-08-15 | 2022-03-22 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| KR102318434B1 (ko) | 2017-08-25 | 2021-11-01 | 스톡 테라퓨틱스, 인크. | 병태 및 질환 치료용 안티센스 올리고머 |
| US10682317B2 (en) | 2017-09-26 | 2020-06-16 | Zogenix International Limited | Ketogenic diet compatible fenfluramine formulation |
| CN111712252A (zh) | 2017-12-13 | 2020-09-25 | 纽约州立大学研究基金会 | 用于治疗疼痛和提高疼痛敏感性的肽和其它药剂 |
| WO2019216919A1 (en) | 2018-05-11 | 2019-11-14 | Zogenix International Limited | Compositions and methods for treating seizure-induced sudden death |
| EP3806834A4 (en) * | 2018-05-25 | 2022-07-27 | The Florey Institute of Neuroscience and Mental Health | DYNAMIC CLAMPS AND METHODS OF USE THEREOF |
| AU2019279856B2 (en) * | 2018-05-29 | 2024-03-07 | Cognizance Biomarkers, Inc. | Biomarkers and methods for evaluation and treatment of epileptic vs non-epileptic seizures / no seizures / psychogenic non-epileptic seizures |
| MX2020012838A (es) | 2018-05-30 | 2021-07-16 | Praxis Prec Medicines Inc | Moduladores de los canales ionicos. |
| BR112021003224A2 (pt) | 2018-08-20 | 2021-07-20 | Rogcon, Inc. | oligonucleotídeos antissentido direcionados a scn2a para o tratamento de encefalopatias por scn1a |
| EA202092908A1 (ru) | 2018-09-28 | 2021-05-14 | Праксис Пресижн Медсинз, Инк. | Модуляторы ионных каналов |
| EA202191079A1 (ru) | 2018-11-19 | 2021-09-20 | Зодженикс Интернэшнл Лимитед | Способы лечения синдрома ретта с применением фенфлурамина |
| AU2020227825B2 (en) | 2019-02-27 | 2026-03-26 | Stoke Therapeutics, Inc. | Antisense oligomers for treatment of conditions and diseases |
| US11773099B2 (en) | 2019-05-28 | 2023-10-03 | Praxis Precision Medicines, Inc. | Compounds and their methods of use |
| US11505554B2 (en) | 2019-05-31 | 2022-11-22 | Praxis Precision Medicines, Inc. | Substituted pyridines as ion channel modulators |
| US11279700B2 (en) | 2019-05-31 | 2022-03-22 | Praxis Precision Medicines, Inc. | Ion channel modulators |
| US11767325B2 (en) | 2019-11-26 | 2023-09-26 | Praxis Precision Medicines, Inc. | Substituted [1,2,4]triazolo[4,3-a]pyrazines as ion channel modulators |
| PE20221280A1 (es) | 2019-11-27 | 2022-09-05 | Praxis Prec Medicines Inc | Formulaciones de moduladores de canales ionicos y metodos de preparacion y uso de moduladores de canales ionicos |
| CN115867657A (zh) | 2020-05-11 | 2023-03-28 | 斯托克制药公司 | 用于治疗疾患和疾病的opa1反义寡聚物 |
| US11612574B2 (en) | 2020-07-17 | 2023-03-28 | Zogenix International Limited | Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) |
| KR20250005348A (ko) | 2022-04-26 | 2025-01-09 | 프락시스 프리시젼 메디신즈, 인크. | 신경 장애의 치료 |
| CN116024222B (zh) * | 2022-11-30 | 2023-12-22 | 湖南家辉生物技术有限公司 | 一种导致婴儿严重肌阵挛性癫痫的nac1基因突变体及其应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4016043A (en) * | 1975-09-04 | 1977-04-05 | Akzona Incorporated | Enzymatic immunological method for the determination of antigens and antibodies |
| US4172124A (en) * | 1978-04-28 | 1979-10-23 | The Wistar Institute | Method of producing tumor antibodies |
| US4474893A (en) * | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| US4971903A (en) * | 1988-03-25 | 1990-11-20 | Edward Hyman | Pyrophosphate-based method and apparatus for sequencing nucleic acids |
| US5331573A (en) * | 1990-12-14 | 1994-07-19 | Balaji Vitukudi N | Method of design of compounds that mimic conformational features of selected peptides |
| US6331614B1 (en) * | 1998-12-23 | 2001-12-18 | Myriad Genetics, Inc. | Human CDC14A gene |
| DE1252330T1 (de) * | 1999-11-26 | 2003-11-27 | Mcgill University, Montreal | Loci der idiopathischen epilepsie, mutationen derselben und verfahren zu deren verwendung zur feststellung, prognose und behandlung von epilepsie |
| US6703439B2 (en) * | 2000-02-09 | 2004-03-09 | Mitsui Chemicals, Inc. | Polyolefin resin composition and polyolefin film prepared from the same |
| AUPQ882600A0 (en) * | 2000-07-18 | 2000-08-10 | Bionomics Limited | Mutations in ion channels |
| AUPR220300A0 (en) * | 2000-12-20 | 2001-01-25 | Bionomics Limited | New epilepsy gene |
| US7282336B2 (en) * | 2001-07-18 | 2007-10-16 | Bionomics Limited | Method of diagnosing epilepsy |
| US7709225B2 (en) * | 2001-07-18 | 2010-05-04 | Bionomics Limited | Nucleic acids encoding mutations in sodium channels related to epilepsy |
| JP2005501536A (ja) * | 2001-07-18 | 2005-01-20 | バイオノミックス リミテッド | イオンチャネルにおける変異 |
| AU2003904154A0 (en) * | 2003-08-07 | 2003-08-21 | Bionomics Limited | Mutations in ion channels |
| US20030157525A1 (en) * | 2001-11-26 | 2003-08-21 | Mintier Gabriel A. | Novel human G-protein coupled receptor, HGPRBMY31, and variants and methods of use thereof |
| AU2003901425A0 (en) * | 2003-03-27 | 2003-04-10 | Bionomics Limited | A diagnostic method for epilepsy |
-
2006
- 2006-06-16 EP EP06741247A patent/EP1904630A4/en not_active Ceased
- 2006-06-16 US US11/922,377 patent/US20100088778A1/en not_active Abandoned
- 2006-06-16 WO PCT/AU2006/000841 patent/WO2006133508A1/en not_active Ceased
- 2006-06-16 JP JP2008516076A patent/JP2008546376A/ja active Pending
- 2006-06-16 CA CA002612180A patent/CA2612180A1/en not_active Abandoned
- 2006-06-16 NZ NZ564892A patent/NZ564892A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008546376A (ja) | 2008-12-25 |
| WO2006133508A1 (en) | 2006-12-21 |
| EP1904630A4 (en) | 2009-10-21 |
| US20100088778A1 (en) | 2010-04-08 |
| EP1904630A1 (en) | 2008-04-02 |
| NZ564892A (en) | 2011-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100088778A1 (en) | Methods of Treatment, and Diagnosis of Epilepsy by Detecting Mutations in the SCN1A Gene | |
| US8288096B2 (en) | Diagnostic method for epilepsy | |
| US7989182B2 (en) | Nucleic acid encoding SCN1A variant | |
| EP1767638A2 (en) | Mutation associated with epilepsy | |
| US8129142B2 (en) | Mutations in ion channels | |
| AU2004200978B2 (en) | A diagnostic method for epilepsy | |
| AU2006257716B2 (en) | Methods of treatment, and diagnosis of epilepsy by detecting mutations in the SCN1A gene | |
| WO2002090532A1 (en) | Novel mutation | |
| WO2005024024A1 (en) | Mutations in the nedd4 gene family in epilepsy and other cns disorders | |
| US20030157535A1 (en) | Identification of two principal mutations in ion channels associated with idiopathic generalised epilepsies | |
| AU2007202499B2 (en) | Mutations in ion channels | |
| AU2004263548B2 (en) | Mutations in ion channels | |
| AU2002252833A1 (en) | Novel mutation | |
| WO2004053128A1 (en) | Mutations in gaba-b receptor 1 associated with epilepsy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |
Effective date: 20150610 |