JP2010527375A - Ｇｐｒ１２の阻害による認知障害の治療方法 - Google Patents
Ｇｐｒ１２の阻害による認知障害の治療方法 Download PDFInfo
- Publication number
- JP2010527375A JP2010527375A JP2010508596A JP2010508596A JP2010527375A JP 2010527375 A JP2010527375 A JP 2010527375A JP 2010508596 A JP2010508596 A JP 2010508596A JP 2010508596 A JP2010508596 A JP 2010508596A JP 2010527375 A JP2010527375 A JP 2010527375A
- Authority
- JP
- Japan
- Prior art keywords
- gpr12
- mammal
- long
- training
- term memory
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 77
- 230000005764 inhibitory process Effects 0.000 title description 14
- 208000028698 Cognitive impairment Diseases 0.000 title description 5
- 208000010877 cognitive disease Diseases 0.000 title description 5
- 101001015106 Homo sapiens G-protein coupled receptor 12 Proteins 0.000 title description 4
- 102100033012 G-protein coupled receptor 12 Human genes 0.000 title description 2
- 101150057121 GPR12 gene Proteins 0.000 claims abstract description 197
- 230000007787 long-term memory Effects 0.000 claims abstract description 70
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 65
- 230000014509 gene expression Effects 0.000 claims abstract description 38
- 210000001320 hippocampus Anatomy 0.000 claims abstract description 32
- 230000001419 dependent effect Effects 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 29
- 230000036992 cognitive tasks Effects 0.000 claims abstract description 27
- 230000006870 function Effects 0.000 claims abstract description 26
- 230000000971 hippocampal effect Effects 0.000 claims abstract description 24
- 229940079593 drug Drugs 0.000 claims abstract description 21
- 238000012549 training Methods 0.000 claims description 97
- 230000015654 memory Effects 0.000 claims description 77
- 241000124008 Mammalia Species 0.000 claims description 53
- 230000000694 effects Effects 0.000 claims description 47
- 230000000692 anti-sense effect Effects 0.000 claims description 26
- 210000004727 amygdala Anatomy 0.000 claims description 17
- 108020004459 Small interfering RNA Proteins 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 238000001514 detection method Methods 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 230000007774 longterm Effects 0.000 claims description 8
- 239000012634 fragment Substances 0.000 claims description 7
- 241000894007 species Species 0.000 claims description 5
- 230000003920 cognitive function Effects 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 abstract description 54
- 102000004169 proteins and genes Human genes 0.000 abstract description 19
- 238000012216 screening Methods 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract 2
- 230000003931 cognitive performance Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 92
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 64
- 241001465754 Metazoa Species 0.000 description 43
- 230000003750 conditioning effect Effects 0.000 description 40
- 210000004027 cell Anatomy 0.000 description 39
- 150000007523 nucleic acids Chemical class 0.000 description 39
- 239000002773 nucleotide Substances 0.000 description 34
- 108020004999 messenger RNA Proteins 0.000 description 33
- 125000003729 nucleotide group Chemical group 0.000 description 31
- 102000039446 nucleic acids Human genes 0.000 description 28
- 108020004707 nucleic acids Proteins 0.000 description 28
- 241000699666 Mus <mouse, genus> Species 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 230000009368 gene silencing by RNA Effects 0.000 description 22
- 239000003112 inhibitor Substances 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- 239000000203 mixture Substances 0.000 description 19
- 108091030071 RNAI Proteins 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 18
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 17
- 108091028043 Nucleic acid sequence Proteins 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 210000004556 brain Anatomy 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 15
- 230000004048 modification Effects 0.000 description 15
- 238000012986 modification Methods 0.000 description 15
- 238000013518 transcription Methods 0.000 description 15
- 230000035897 transcription Effects 0.000 description 15
- 210000003169 central nervous system Anatomy 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 208000006011 Stroke Diseases 0.000 description 12
- 230000006399 behavior Effects 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 230000008014 freezing Effects 0.000 description 12
- 238000007710 freezing Methods 0.000 description 12
- 238000011813 knockout mouse model Methods 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 230000032683 aging Effects 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 230000035939 shock Effects 0.000 description 10
- 229920002873 Polyethylenimine Polymers 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 8
- 210000002569 neuron Anatomy 0.000 description 8
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 7
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 7
- 108010001267 Protein Subunits Proteins 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 229940124452 immunizing agent Drugs 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- -1 regulatory sequences Proteins 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 101150005734 CREB1 gene Proteins 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 101150021949 GRIN1 gene Proteins 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 238000000692 Student's t-test Methods 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000001771 impaired effect Effects 0.000 description 5
- 230000002452 interceptive effect Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000006403 short-term memory Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 102100031780 Endonuclease Human genes 0.000 description 4
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 4
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 4
- 102000002067 Protein Subunits Human genes 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 108091081021 Sense strand Proteins 0.000 description 4
- 102000006467 TATA-Box Binding Protein Human genes 0.000 description 4
- 108010044281 TATA-Box Binding Protein Proteins 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000001054 cortical effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 230000006390 fear memory Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 230000002123 temporal effect Effects 0.000 description 4
- 210000001103 thalamus Anatomy 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 108700028369 Alleles Proteins 0.000 description 3
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
- 101150083770 Gpr3 gene Proteins 0.000 description 3
- 101150014072 Gpr6 gene Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 208000026139 Memory disease Diseases 0.000 description 3
- 101100337650 Mus musculus Gpr12 gene Proteins 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000000478 neocortex Anatomy 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 125000002652 ribonucleotide group Chemical group 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- JLVSPVFPBBFMBE-HXSWCURESA-O sphingosylphosphocholine acid Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H]([NH3+])COP([O-])(=O)OCC[N+](C)(C)C JLVSPVFPBBFMBE-HXSWCURESA-O 0.000 description 3
- 210000003594 spinal ganglia Anatomy 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 244000291564 Allium cepa Species 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 241000289695 Eutheria Species 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 2
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 2
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 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 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 108091036078 conserved sequence Proteins 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000006274 endogenous ligand Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000005802 health problem Effects 0.000 description 2
- 102000046099 human GPR12 Human genes 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000007334 memory performance Effects 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 108091008880 orphan GPCRs Proteins 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012660 pharmacological inhibitor Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 239000008149 soap solution Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012250 transgenic expression Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 102000007445 2',5'-Oligoadenylate Synthetase Human genes 0.000 description 1
- 108010086241 2',5'-Oligoadenylate Synthetase Proteins 0.000 description 1
- 102100027962 2-5A-dependent ribonuclease Human genes 0.000 description 1
- 108010000834 2-5A-dependent ribonuclease Proteins 0.000 description 1
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 208000009575 Angelman syndrome Diseases 0.000 description 1
- 241000237967 Aplysia Species 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 244000089409 Erythrina poeppigiana Species 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 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
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010021033 Hypomenorrhoea Diseases 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 201000000251 Locked-in syndrome Diseases 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 238000012347 Morris Water Maze Methods 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 108010057163 Ribonuclease III Proteins 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 229940059260 amidate Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007585 cortical function Effects 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 210000005110 dorsal hippocampus Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000550 effect on aging Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000009762 endothelial cell differentiation Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000008801 hippocampal function Effects 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000031864 metaphase Effects 0.000 description 1
- MCPLVIGCWWTHFH-UHFFFAOYSA-L methyl blue Chemical compound [Na+].[Na+].C1=CC(S(=O)(=O)[O-])=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[NH+]C=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S([O-])(=O)=O)=CC=2)C=C1 MCPLVIGCWWTHFH-UHFFFAOYSA-L 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001343 mnemonic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000000977 primary visual cortex Anatomy 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000005067 remediation Methods 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Neurosurgery (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93816307P | 2007-05-15 | 2007-05-15 | |
| PCT/US2008/063804 WO2008144453A1 (en) | 2007-05-15 | 2008-05-15 | Methods of treating cognitive disorders by inhibition of gpr12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010527375A true JP2010527375A (ja) | 2010-08-12 |
| JP2010527375A5 JP2010527375A5 (enExample) | 2011-06-23 |
Family
ID=40122145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010508596A Pending JP2010527375A (ja) | 2007-05-15 | 2008-05-15 | Ｇｐｒ１２の阻害による認知障害の治療方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7968524B2 (enExample) |
| EP (1) | EP2162137B1 (enExample) |
| JP (1) | JP2010527375A (enExample) |
| KR (1) | KR20100029079A (enExample) |
| CN (1) | CN101808647A (enExample) |
| AU (1) | AU2008254905A1 (enExample) |
| BR (1) | BRPI0811625A2 (enExample) |
| CA (1) | CA2684920A1 (enExample) |
| IL (1) | IL202091A0 (enExample) |
| MX (1) | MX2009012316A (enExample) |
| WO (1) | WO2008144453A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102458435A (zh) | 2009-04-09 | 2012-05-16 | 考格尼申治疗股份有限公司 | 认知衰退的抑制剂 |
| SG178191A1 (en) | 2009-07-31 | 2012-03-29 | Cognition Therapeutics Inc | Inhibitors of cognitive decline |
| WO2011106785A2 (en) * | 2010-02-26 | 2011-09-01 | Cognition Therapeutics, Inc. | Methods of identifying agents effective to treat cognitive decline and diseases associated therewith |
| CN103458885B (zh) | 2011-02-02 | 2016-02-10 | 考格尼申治疗股份有限公司 | 由姜黄油分离的化合物及使用方法 |
| JP6517827B2 (ja) | 2014-01-31 | 2019-05-22 | コグニション セラピューティクス，インコーポレイテッド | イソインドリン組成物および神経変性疾患の治療方法 |
| CA3061787A1 (en) | 2017-05-15 | 2018-11-22 | Cognition Therapeutics, Inc. | Compositions for treating neurodegenerative diseases |
| BR102022009685A2 (pt) * | 2022-05-18 | 2023-11-28 | Fundação Oswaldo Cruz | Método para triagem de fármacos ou substâncias com potencial neuroprotetor, kit para triagem de fármacos ou substâncias, e, uso de um painel de genes |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003518628A (ja) * | 1999-12-10 | 2003-06-10 | アストラゼネカ アクチボラグ | 化合物 |
| US20040023384A1 (en) * | 2002-07-31 | 2004-02-05 | Isis Pharmaceuticals Inc. | Antisense modulation of G protein-coupled receptor 12 expression |
| WO2004038407A2 (en) * | 2002-10-24 | 2004-05-06 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human g-protein coupled receptor 12 (gpr12) |
| WO2005103713A2 (en) * | 2004-04-20 | 2005-11-03 | Galapagos N.V. | Methods, compositions and compound assays for inhibiting amyloid-beta protein production |
| JP2006524243A (ja) * | 2003-04-08 | 2006-10-26 | コールド スプリング ハーバー ラボラトリー | 増強認知訓練 |
| JP2007505617A (ja) * | 2003-09-19 | 2007-03-15 | パラダイム・セラピューティクス・リミテッド | 受容体 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100334858B1 (ko) | 1993-02-19 | 2006-01-27 | 니뽄 신야쿠 가부시키가이샤 | 핵산공중합체를함유하는의약조성물 |
| US6291438B1 (en) | 1993-02-24 | 2001-09-18 | Jui H. Wang | Antiviral anticancer poly-substituted phenyl derivatized oligoribonucleotides and methods for their use |
| US5858988A (en) | 1993-02-24 | 1999-01-12 | Wang; Jui H. | Poly-substituted-phenyl-oligoribo nucleotides having enhanced stability and membrane permeability and methods of use |
| US5877399A (en) * | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| EP0755454B1 (en) | 1994-04-13 | 2008-02-13 | The Rockefeller University | Aav-mediated delivery of dna to cells of the nervous system |
| US5684143A (en) | 1996-02-21 | 1997-11-04 | Lynx Therapeutics, Inc. | Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates |
| US6653086B1 (en) * | 1998-04-14 | 2003-11-25 | Arena Pharmaceuticals, Inc. | Endogenous constitutively activated G protein-coupled orphan receptors |
| US20060247194A1 (en) | 2000-08-30 | 2006-11-02 | Sirna Therapeutics , Inc. | Rna interference mediated treatment of alzheimer's disease using short interfering nucleic acid (sina) |
| RU2322500C2 (ru) * | 2000-12-01 | 2008-04-20 | Макс-Планк-Гезелльшафт Цур Фердерунг Дер Виссеншафтен Е.Ф. | Малые молекулы рнк, опосредующие интерференцию рнк |
| US6586524B2 (en) | 2001-07-19 | 2003-07-01 | Expression Genetics, Inc. | Cellular targeting poly(ethylene glycol)-grafted polymeric gene carrier |
| US20050106731A1 (en) | 2002-08-05 | 2005-05-19 | Davidson Beverly L. | siRNA-mediated gene silencing with viral vectors |
| WO2004014933A1 (en) | 2002-08-07 | 2004-02-19 | University Of Massachusetts | Compositions for rna interference and methods of use thereof |
| US7829694B2 (en) * | 2002-11-26 | 2010-11-09 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
| US20070104688A1 (en) | 2003-02-13 | 2007-05-10 | City Of Hope | Small interfering RNA mediated transcriptional gene silencing in mammalian cells |
-
2008
- 2008-05-15 BR BRPI0811625-3A2A patent/BRPI0811625A2/pt not_active IP Right Cessation
- 2008-05-15 CN CN200880023965A patent/CN101808647A/zh active Pending
- 2008-05-15 EP EP08755619.7A patent/EP2162137B1/en not_active Not-in-force
- 2008-05-15 CA CA002684920A patent/CA2684920A1/en not_active Abandoned
- 2008-05-15 JP JP2010508596A patent/JP2010527375A/ja active Pending
- 2008-05-15 MX MX2009012316A patent/MX2009012316A/es unknown
- 2008-05-15 WO PCT/US2008/063804 patent/WO2008144453A1/en not_active Ceased
- 2008-05-15 KR KR1020097024747A patent/KR20100029079A/ko not_active Withdrawn
- 2008-05-15 AU AU2008254905A patent/AU2008254905A1/en not_active Abandoned
- 2008-05-15 US US12/121,731 patent/US7968524B2/en not_active Expired - Fee Related
-
2009
- 2009-11-12 IL IL202091A patent/IL202091A0/en unknown
-
2011
- 2011-06-27 US US13/169,739 patent/US20110281936A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003518628A (ja) * | 1999-12-10 | 2003-06-10 | アストラゼネカ アクチボラグ | 化合物 |
| US20040023384A1 (en) * | 2002-07-31 | 2004-02-05 | Isis Pharmaceuticals Inc. | Antisense modulation of G protein-coupled receptor 12 expression |
| WO2004038407A2 (en) * | 2002-10-24 | 2004-05-06 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with human g-protein coupled receptor 12 (gpr12) |
| JP2006524243A (ja) * | 2003-04-08 | 2006-10-26 | コールド スプリング ハーバー ラボラトリー | 増強認知訓練 |
| JP2007505617A (ja) * | 2003-09-19 | 2007-03-15 | パラダイム・セラピューティクス・リミテッド | 受容体 |
| WO2005103713A2 (en) * | 2004-04-20 | 2005-11-03 | Galapagos N.V. | Methods, compositions and compound assays for inhibiting amyloid-beta protein production |
Also Published As
| Publication number | Publication date |
|---|---|
| US20110281936A1 (en) | 2011-11-17 |
| US20090022667A1 (en) | 2009-01-22 |
| US7968524B2 (en) | 2011-06-28 |
| KR20100029079A (ko) | 2010-03-15 |
| CA2684920A1 (en) | 2008-11-27 |
| BRPI0811625A2 (pt) | 2014-11-11 |
| WO2008144453A1 (en) | 2008-11-27 |
| CN101808647A (zh) | 2010-08-18 |
| AU2008254905A1 (en) | 2008-11-27 |
| EP2162137A4 (en) | 2011-06-08 |
| WO2008144453A9 (en) | 2010-03-18 |
| EP2162137B1 (en) | 2016-11-23 |
| EP2162137A1 (en) | 2010-03-17 |
| IL202091A0 (en) | 2010-06-16 |
| MX2009012316A (es) | 2009-12-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI543763B (zh) | Ｈｓｐ４７表現之調節 | |
| JP2010527243A (ja) | 低分子干渉ＲＮＡ（ｓｉＲＮＡ）を用いた記憶形成に関わる遺伝子の同定方法 | |
| CN101557831A (zh) | 体内抑制在灵长类亨廷顿基因表达的方法和序列 | |
| US7968524B2 (en) | Methods of enhancing long term memory formation by inhibition of Gpr12 | |
| US9359607B2 (en) | Methods of diagnosing and treating motor neuron diseases | |
| JP2011015695A (ja) | Ｎａｖ１．８の短い干渉核酸阻害のための組成物および方法 | |
| TW200808360A (en) | RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions | |
| WO2016044929A1 (en) | Microrna-132/212 for the treatment of neurodegenerative disorders | |
| US20080249038A1 (en) | Bone Morphogenetic Protein (Bmp) 2A and Uses Thereof | |
| EP3037817B1 (en) | Screening method for pain suppressors and pharmaceutical composition for prevention or treatment of pain | |
| US20160083731A1 (en) | APTAMER-RNAi THERAPEUTIC COMPOSITIONS | |
| HK1250243A1 (zh) | 治疗方法 | |
| CN113302302A (zh) | 双链rna及其用途 | |
| TW200808328A (en) | RNAi-mediated inhibition of stromal cell-derived factor 1-related targets for treatment of neovascularization-related conditions | |
| WO2025068557A1 (en) | Antisense oligonucleotides for the treatment of canavan disease | |
| EP4642913A2 (en) | Splice-switching oligonucleotides for treating syngap1-associated disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110509 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110509 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130227 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130716 |