JP2012524725A - ハンチントン病を治療するための組織カリクレイン - Google Patents
ハンチントン病を治療するための組織カリクレイン Download PDFInfo
- Publication number
- JP2012524725A JP2012524725A JP2012506297A JP2012506297A JP2012524725A JP 2012524725 A JP2012524725 A JP 2012524725A JP 2012506297 A JP2012506297 A JP 2012506297A JP 2012506297 A JP2012506297 A JP 2012506297A JP 2012524725 A JP2012524725 A JP 2012524725A
- Authority
- JP
- Japan
- Prior art keywords
- klk1
- disease
- seq
- huntington
- variant
- 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
- 208000023105 Huntington disease Diseases 0.000 title claims abstract description 113
- 101710176219 Kallikrein-1 Proteins 0.000 title claims abstract description 73
- 102000057032 Tissue Kallikreins Human genes 0.000 title claims abstract description 59
- 239000012634 fragment Substances 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 38
- 208000024891 symptom Diseases 0.000 claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 208000025069 Juvenile Huntington disease Diseases 0.000 claims abstract description 25
- 208000037048 Prodromal Symptoms Diseases 0.000 claims abstract description 9
- 102100038297 Kallikrein-1 Human genes 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 20
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 claims description 19
- 101100453988 Homo sapiens KLK1 gene Proteins 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 8
- 241000283073 Equus caballus Species 0.000 claims description 6
- 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 claims description 5
- 241000283690 Bos taurus Species 0.000 claims description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 4
- 241001504519 Papio ursinus Species 0.000 claims description 4
- 241001494479 Pecora Species 0.000 claims description 4
- 241000288961 Saguinus imperator Species 0.000 claims description 4
- RCRODHONKLSMIF-UHFFFAOYSA-N isosuberenol Natural products O1C(=O)C=CC2=C1C=C(OC)C(CC(O)C(C)=C)=C2 RCRODHONKLSMIF-UHFFFAOYSA-N 0.000 claims description 4
- 101100453989 Macaca fascicularis KLK1 gene Proteins 0.000 claims description 3
- 108700022175 Tissue Kallikreins Proteins 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 102000001399 Kallikrein Human genes 0.000 description 55
- 108060005987 Kallikrein Proteins 0.000 description 55
- 210000004556 brain Anatomy 0.000 description 50
- 108090000765 processed proteins & peptides Proteins 0.000 description 39
- 102000004196 processed proteins & peptides Human genes 0.000 description 33
- 150000001413 amino acids Chemical group 0.000 description 31
- 229920001184 polypeptide Polymers 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 201000010099 disease Diseases 0.000 description 19
- 239000000843 powder Substances 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
- 150000007523 nucleic acids Chemical group 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 230000033001 locomotion Effects 0.000 description 13
- 210000002569 neuron Anatomy 0.000 description 13
- 239000000411 inducer Substances 0.000 description 12
- 238000002595 magnetic resonance imaging Methods 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 229960003624 creatine Drugs 0.000 description 10
- 239000006046 creatine Substances 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 210000001577 neostriatum Anatomy 0.000 description 10
- 230000004770 neurodegeneration Effects 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 9
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 9
- 230000019522 cellular metabolic process Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 210000003928 nasal cavity Anatomy 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- 230000017531 blood circulation Effects 0.000 description 8
- 230000004190 glucose uptake Effects 0.000 description 8
- 230000004766 neurogenesis Effects 0.000 description 8
- 239000007921 spray Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 7
- OTCCIMWXFLJLIA-UHFFFAOYSA-N N-acetyl-DL-aspartic acid Natural products CC(=O)NC(C(O)=O)CC(O)=O OTCCIMWXFLJLIA-UHFFFAOYSA-N 0.000 description 7
- OTCCIMWXFLJLIA-BYPYZUCNSA-N N-acetyl-L-aspartic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(O)=O OTCCIMWXFLJLIA-BYPYZUCNSA-N 0.000 description 7
- 108010025020 Nerve Growth Factor Proteins 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 239000003963 antioxidant agent Substances 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 230000002438 mitochondrial effect Effects 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 6
- GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 6
- 108700028369 Alleles Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 6
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 6
- 229960003151 mercaptamine Drugs 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 102000007072 Nerve Growth Factors Human genes 0.000 description 5
- 230000005856 abnormality Effects 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000002424 anti-apoptotic effect Effects 0.000 description 5
- 230000004900 autophagic degradation Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 208000010877 cognitive disease Diseases 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 239000003900 neurotrophic factor Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- 206010003694 Atrophy Diseases 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- 102000016252 Huntingtin Human genes 0.000 description 4
- 108050004784 Huntingtin Proteins 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 230000037444 atrophy Effects 0.000 description 4
- 210000004227 basal ganglia Anatomy 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 210000003710 cerebral cortex Anatomy 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 235000015872 dietary supplement Nutrition 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- 230000004065 mitochondrial dysfunction Effects 0.000 description 4
- 229940127237 mood stabilizer Drugs 0.000 description 4
- 239000004050 mood stabilizer Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- UMFJAHHVKNCGLG-UHFFFAOYSA-N n-Nitrosodimethylamine Chemical compound CN(C)N=O UMFJAHHVKNCGLG-UHFFFAOYSA-N 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 238000011132 neural stem cell therapy Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- -1 onocrein P Proteins 0.000 description 4
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 230000009747 swallowing Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 3
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 3
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 3
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
- GLQPTZAAUROJMO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)benzaldehyde Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC=C(C=O)C=C1 GLQPTZAAUROJMO-UHFFFAOYSA-N 0.000 description 3
- 108030001720 Bontoxilysin Proteins 0.000 description 3
- 208000024806 Brain atrophy Diseases 0.000 description 3
- 206010008748 Chorea Diseases 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
- 206010013887 Dysarthria Diseases 0.000 description 3
- 229920000064 Ethyl eicosapentaenoic acid Polymers 0.000 description 3
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 108010003195 Kallidin Proteins 0.000 description 3
- FYSKZKQBTVLYEQ-FSLKYBNLSA-N Kallidin Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 FYSKZKQBTVLYEQ-FSLKYBNLSA-N 0.000 description 3
- 102100035792 Kininogen-1 Human genes 0.000 description 3
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100021584 Neurturin Human genes 0.000 description 3
- 108010015406 Neurturin Proteins 0.000 description 3
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 3
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 3
- 108091030071 RNAI Proteins 0.000 description 3
- BHTRKEVKTKCXOH-UHFFFAOYSA-N Taurochenodesoxycholsaeure Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)CC2 BHTRKEVKTKCXOH-UHFFFAOYSA-N 0.000 description 3
- 229960004308 acetylcysteine Drugs 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 230000000561 anti-psychotic effect Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000008335 axon cargo transport Effects 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940053031 botulinum toxin Drugs 0.000 description 3
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 3
- 229960000623 carbamazepine Drugs 0.000 description 3
- 229940123098 caspase 6 inhibitor Drugs 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000003727 cerebral blood flow Effects 0.000 description 3
- 229960001076 chlorpromazine Drugs 0.000 description 3
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 208000012601 choreatic disease Diseases 0.000 description 3
- 229960001653 citalopram Drugs 0.000 description 3
- 229960002896 clonidine Drugs 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 210000001947 dentate gyrus Anatomy 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- SSQPWTVBQMWLSZ-AAQCHOMXSA-N ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate Chemical compound CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC SSQPWTVBQMWLSZ-AAQCHOMXSA-N 0.000 description 3
- 230000003492 excitotoxic effect Effects 0.000 description 3
- 231100000063 excitotoxicity Toxicity 0.000 description 3
- 229960002464 fluoxetine Drugs 0.000 description 3
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 210000004907 gland Anatomy 0.000 description 3
- 229960003878 haloperidol Drugs 0.000 description 3
- 101150113725 hd gene Proteins 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 3
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 3
- 239000003290 indole 3-propionic acid Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 229960001078 lithium Drugs 0.000 description 3
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 3
- 229960004640 memantine Drugs 0.000 description 3
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 3
- 229960004083 methazolamide Drugs 0.000 description 3
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 3
- 229960004023 minocycline Drugs 0.000 description 3
- 239000003158 myorelaxant agent Substances 0.000 description 3
- 239000007923 nasal drop Substances 0.000 description 3
- 229940100662 nasal drops Drugs 0.000 description 3
- 230000007433 nerve pathway Effects 0.000 description 3
- 229960001158 nortriptyline Drugs 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 229960005017 olanzapine Drugs 0.000 description 3
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 3
- 210000000196 olfactory nerve Anatomy 0.000 description 3
- 229960002296 paroxetine Drugs 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 229960003660 sertraline hydrochloride Drugs 0.000 description 3
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- BHTRKEVKTKCXOH-LBSADWJPSA-N tauroursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-LBSADWJPSA-N 0.000 description 3
- 229960005333 tetrabenazine Drugs 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 239000003204 tranquilizing agent Substances 0.000 description 3
- 230000002936 tranquilizing effect Effects 0.000 description 3
- 229940102566 valproate Drugs 0.000 description 3
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 3
- 229960004688 venlafaxine Drugs 0.000 description 3
- 229960001722 verapamil Drugs 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- VUAFHZCUKUDDBC-SCSAIBSYSA-N (2s)-2-[(2-methyl-2-sulfanylpropanoyl)amino]-3-sulfanylpropanoic acid Chemical compound CC(C)(S)C(=O)N[C@H](CS)C(O)=O VUAFHZCUKUDDBC-SCSAIBSYSA-N 0.000 description 2
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 208000000187 Abnormal Reflex Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 102100037373 DNA-(apurinic or apyrimidinic site) endonuclease Human genes 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 206010012239 Delusion Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 2
- 108700019745 Disks Large Homolog 4 Proteins 0.000 description 2
- 102000047174 Disks Large Homolog 4 Human genes 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 208000014094 Dystonic disease Diseases 0.000 description 2
- 101710088570 Flagellar hook-associated protein 1 Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 206010017577 Gait disturbance Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010021034 Hypometabolism Diseases 0.000 description 2
- 108010077861 Kininogens Proteins 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 2
- 102400000966 Lysyl-bradykinin Human genes 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 206010061296 Motor dysfunction Diseases 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- 101001050269 Mus musculus Kallikrein 1-related peptidase b1 Proteins 0.000 description 2
- 206010028289 Muscle atrophy Diseases 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 206010033864 Paranoia Diseases 0.000 description 2
- 208000027099 Paranoid disease Diseases 0.000 description 2
- 206010034719 Personality change Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 208000001431 Psychomotor Agitation Diseases 0.000 description 2
- 206010038743 Restlessness Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004598 abnormal eye movement Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229960004272 bucillamine Drugs 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 231100000868 delusion Toxicity 0.000 description 2
- 238000001784 detoxification Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 2
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 230000007185 extracellular pathway Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 206010020745 hyperreflexia Diseases 0.000 description 2
- 230000035859 hyperreflexia Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000000366 juvenile effect Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- 230000004973 motor coordination Effects 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 230000006576 neuronal survival Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000000508 neurotrophic effect Effects 0.000 description 2
- 210000001706 olfactory mucosa Anatomy 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000012831 peritoneal equilibrium test Methods 0.000 description 2
- 239000003186 pharmaceutical solution Substances 0.000 description 2
- 238000012636 positron electron tomography Methods 0.000 description 2
- 238000012877 positron emission topography Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010079 rubber tapping Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940125725 tranquilizer Drugs 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 229940029284 trichlorofluoromethane Drugs 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 230000002747 voluntary effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 101100191768 Caenorhabditis elegans pbs-4 gene Proteins 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 102100027823 Complexin-2 Human genes 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000019205 Dynactin Complex Human genes 0.000 description 1
- 108010012830 Dynactin Complex Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- BPNZYADGDZPRTK-UDUYQYQQSA-N Exametazime Chemical compound O/N=C(\C)[C@@H](C)NCC(C)(C)CN[C@H](C)C(\C)=N\O BPNZYADGDZPRTK-UDUYQYQQSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 1
- 101001021527 Homo sapiens Huntingtin-interacting protein 1 Proteins 0.000 description 1
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 1
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 1
- 101000756346 Homo sapiens RE1-silencing transcription factor Proteins 0.000 description 1
- 101000644689 Homo sapiens Ubiquitin-conjugating enzyme E2 K Proteins 0.000 description 1
- 102100035957 Huntingtin-interacting protein 1 Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 150000007649 L alpha amino acids Chemical class 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 102000011965 Lipoprotein Receptors Human genes 0.000 description 1
- 108010061306 Lipoprotein Receptors Proteins 0.000 description 1
- 206010024870 Loss of libido Diseases 0.000 description 1
- 101000605521 Macaca fascicularis Kallikrein-1 Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- IMWZZHHPURKASS-UHFFFAOYSA-N Metaxalone Chemical compound CC1=CC(C)=CC(OCC2OC(=O)NC2)=C1 IMWZZHHPURKASS-UHFFFAOYSA-N 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- 238000012879 PET imaging Methods 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100022940 RE1-silencing transcription factor Human genes 0.000 description 1
- 101000605527 Rattus norvegicus Kallikrein-1 Proteins 0.000 description 1
- 102000034527 Retinoid X Receptors Human genes 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- 235000011449 Rosa Nutrition 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 102100020696 Ubiquitin-conjugating enzyme E2 K Human genes 0.000 description 1
- 102000003786 Vesicle-associated membrane protein 2 Human genes 0.000 description 1
- 108090000169 Vesicle-associated membrane protein 2 Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 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
- 230000002411 adverse Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 208000019290 autosomal genetic disease Diseases 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000006736 behavioral deficit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- OFZCIYFFPZCNJE-UHFFFAOYSA-N carisoprodol Chemical compound NC(=O)OCC(C)(CCC)COC(=O)NC(C)C OFZCIYFFPZCNJE-UHFFFAOYSA-N 0.000 description 1
- 229960004587 carisoprodol Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006567 cellular energy metabolism Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 108010062428 complexin II Proteins 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 1
- 229960003572 cyclobenzaprine Drugs 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- WQZGKKKJIJFFOK-UKLRSMCWSA-N dextrose-2-13c Chemical compound OC[C@H]1OC(O)[13C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-UKLRSMCWSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 101150069842 dlg4 gene Proteins 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 210000005110 dorsal hippocampus Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000006195 histone acetylation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000003140 lateral ventricle Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 230000006677 mitochondrial metabolism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 229940100652 nasal gel Drugs 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 229940100657 nasal ointment Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000010004 neural pathway Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000017511 neuron migration Effects 0.000 description 1
- 238000011859 neuroprotective therapy Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 210000004415 olfactory epithelial cell Anatomy 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 108010040003 polyglutamine Proteins 0.000 description 1
- 229920000155 polyglutamine Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 229940105580 skelaxin Drugs 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000000264 spin echo pulse sequence Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010245 stereological analysis Methods 0.000 description 1
- 238000004326 stimulated echo acquisition mode for imaging Methods 0.000 description 1
- 210000002330 subarachnoid space Anatomy 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000007755 survival signaling Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000001927 transneuronal effect Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 230000028973 vesicle-mediated transport Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4853—Kallikrein (3.4.21.34 or 3.4.21.35)
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17157909P | 2009-04-22 | 2009-04-22 | |
| US61/171,579 | 2009-04-22 | ||
| PCT/CA2010/000575 WO2010121361A1 (en) | 2009-04-22 | 2010-04-22 | Tissue kallikrein for the treatment of huntington's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012524725A true JP2012524725A (ja) | 2012-10-18 |
| JP2012524725A5 JP2012524725A5 (enExample) | 2013-05-30 |
Family
ID=43010630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012506297A Pending JP2012524725A (ja) | 2009-04-22 | 2010-04-22 | ハンチントン病を治療するための組織カリクレイン |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20120225051A1 (enExample) |
| EP (1) | EP2421554A4 (enExample) |
| JP (1) | JP2012524725A (enExample) |
| CN (1) | CN102458454A (enExample) |
| CA (1) | CA2759490A1 (enExample) |
| WO (1) | WO2010121361A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2025504043A (ja) * | 2022-01-28 | 2025-02-06 | 江蘇衆紅生物工程創薬研究院有限公司 | Ｖｃｉ、ｐｓｃｉまたはｃｓｖｄの治療におけるカリクレイン１またはその誘導体の使用 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8501695B2 (en) | 2007-07-20 | 2013-08-06 | Diamedica, Inc. | Tissue kallikrein for the treatment of diseases associated with amyloid protein |
| US20130315891A1 (en) * | 2012-05-25 | 2013-11-28 | Matthew Charles | Formulations of human tissue kallikrein-1 for parenteral delivery and related methods |
| CA2880085C (en) | 2012-06-04 | 2021-09-07 | Diamedica Inc. | Human tissue kallikrein 1 glycosylation isoforms |
| WO2015109107A1 (en) * | 2014-01-15 | 2015-07-23 | Cal Poly Pomona Foundation, Inc. | Treatment and diagnosis of huntington's disease |
| EP3592377A4 (en) | 2017-03-09 | 2021-02-17 | Diamedica Inc. | TISSUE KALLICREIN DOSAGE FORMS 1 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001056532A2 (en) * | 2000-02-04 | 2001-08-09 | The Scripps Research Institute | Neuroprotective, antithrombotic and anti-inflammatory uses of activated protein c (apc) |
| EP1664790A2 (en) * | 2003-08-30 | 2006-06-07 | Bayer HealthCare AG | Diagnostics and therapeutics for diseases associated with kallikrein 8 (klk8) |
| WO2005022146A2 (en) * | 2003-08-30 | 2005-03-10 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with kallikrein 13 (klk13) |
| US8501695B2 (en) * | 2007-07-20 | 2013-08-06 | Diamedica, Inc. | Tissue kallikrein for the treatment of diseases associated with amyloid protein |
-
2010
- 2010-04-22 US US13/265,357 patent/US20120225051A1/en not_active Abandoned
- 2010-04-22 CN CN2010800275339A patent/CN102458454A/zh active Pending
- 2010-04-22 JP JP2012506297A patent/JP2012524725A/ja active Pending
- 2010-04-22 CA CA2759490A patent/CA2759490A1/en not_active Abandoned
- 2010-04-22 EP EP10766547A patent/EP2421554A4/en not_active Withdrawn
- 2010-04-22 WO PCT/CA2010/000575 patent/WO2010121361A1/en not_active Ceased
Non-Patent Citations (5)
| Title |
|---|
| JPN6014016652; Ｊｏｕｒｎａｌ ｏｆ Ｂｉｏｌｏｇｉｃａｌ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．２８０，Ｎｏ．２３, 2005, ｐ２２０２１-２２０２８ * |
| JPN6014016655; Ｄｅｖｅｌｏｐｍｅｎｔａｌ Ｃｅｌｌ Ｖｏｌ．２，Ｎｏ．６, 2002, ｐ８３１-８３７ * |
| JPN6014016658; Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｎｅｕｒｏｓｃｉｅｎｃｅ Ｖｏｌ．２１，Ｎｏ．６, 2005, ｐ１４７８-１４８８ * |
| JPN6014016661; Ｈｕｍａｎ Ｇｅｎｅ Ｔｈｅｒａｐｙ Ｖｏｌ．１７，Ｎｏ．２, 2006, ｐ２０６-２１９ * |
| JPN6014016663; Ｈｙｐｅｒｔｅｎｓｉｏｎ Ｖｏｌ．４３，Ｎｏ．２, 2004, ｐ４５２-４５９ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2025504043A (ja) * | 2022-01-28 | 2025-02-06 | 江蘇衆紅生物工程創薬研究院有限公司 | Ｖｃｉ、ｐｓｃｉまたはｃｓｖｄの治療におけるカリクレイン１またはその誘導体の使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102458454A (zh) | 2012-05-16 |
| WO2010121361A1 (en) | 2010-10-28 |
| US20120225051A1 (en) | 2012-09-06 |
| CA2759490A1 (en) | 2010-10-28 |
| EP2421554A4 (en) | 2012-11-28 |
| EP2421554A1 (en) | 2012-02-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2021176883A (ja) | 老化関連症状を治療する方法のために使用される医薬組成物 | |
| US11241483B2 (en) | Methods of treating mild brain injury | |
| US20120276019A1 (en) | Tissue kallikrein for the treatment of parkinson's disease | |
| JP2012524725A (ja) | ハンチントン病を治療するための組織カリクレイン | |
| US20110150781A1 (en) | Tissue kallikrein for the treatment of parkinson's disease | |
| JP2019506439A (ja) | ターゲティングされた治療用リソソーム酵素融合タンパク質、関連する製剤、およびその使用 | |
| WO2016134215A1 (en) | Methods of treating mild brain injury and post-traumatic stress disorder | |
| US20240100076A1 (en) | Methods and compositions for treating neurodegenerative diseases | |
| AU2017306558A1 (en) | Reelin compositions for treatment of neurological disorders | |
| Wang et al. | Nitric oxide/cyclic guanosine monophosphate signaling via guanylyl cyclase isoform 1 mediates early changes in synaptic transmission and brain edema formation after traumatic brain injury | |
| Antushevich et al. | Apelin's effects on young rat gastrointestinal tract maturation | |
| KR20040008177A (ko) | 신경 사 단백질 세그먼트를 사용하여 세포 사멸을억제하는 방법 | |
| US20080039381A1 (en) | Lactalbumin for Inhibiting Angiogenesis | |
| CA3190919C (en) | Peptide composition for prevention or treatment of alzheimer's disease | |
| Desmoulins et al. | A subset of neurons in the paraventricular nucleus of the hypothalamus directly project to liver-related premotor neurons in the ventrolateral medulla | |
| US20180117113A1 (en) | Amidated Dopamine Neuron Stimulating Peptide Restoration of Mitochondrial Activity | |
| PT101051A (pt) | Uso de nt-3, de anticorpo neutralizante anti-nt-3 e de molecula de ribozima ou anti-sentido no fabrico de um medicamento para o tratamento de desordens do sistema nervoso e processo de analise relacionados com nt-3 | |
| US20110178025A1 (en) | Amidated Dopamine Neuron Stimulating Peptides for CNS Dopaminergic Upregulation | |
| JP5784754B2 (ja) | 神経疾患の予防または処置のためのｉｃａｍ−１の使用 | |
| Park et al. | Aerobic exercise during exposure to 40Hz light flicker protects against early cognitive impairments in Alzheimer’s disease of 3xTg mice | |
| Yang et al. | GPX4 Promotes Optic Nerve Regeneration and RGC Neuroprotection | |
| Bruno | Morphofunctional impairment of neuronal and glial cells in the developing cerebellum of a mouse model of Niemann-Pick type C1 disease | |
| Valér Csernus | Andrea Tamás MD | |
| EA045597B1 (ru) | Композиции рилина для лечения неврологических расстройств |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130405 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130405 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140428 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141125 |