AU2008286361B2 - IVIG modulation of chemokines for treatment of multiple sclerosis, Alzheimer's disease, and Parkinson's disease - Google Patents
IVIG modulation of chemokines for treatment of multiple sclerosis, Alzheimer's disease, and Parkinson's disease Download PDFInfo
- Publication number
- AU2008286361B2 AU2008286361B2 AU2008286361A AU2008286361A AU2008286361B2 AU 2008286361 B2 AU2008286361 B2 AU 2008286361B2 AU 2008286361 A AU2008286361 A AU 2008286361A AU 2008286361 A AU2008286361 A AU 2008286361A AU 2008286361 B2 AU2008286361 B2 AU 2008286361B2
- Authority
- AU
- Australia
- Prior art keywords
- disease
- multiple sclerosis
- ivig
- parkinson
- alzheimer
- 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.)
- Ceased
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 42
- 208000018737 Parkinson disease Diseases 0.000 title claims abstract description 40
- 201000006417 multiple sclerosis Diseases 0.000 title claims description 108
- 102000019034 Chemokines Human genes 0.000 title claims description 57
- 108010012236 Chemokines Proteins 0.000 title claims description 57
- 238000011282 treatment Methods 0.000 title abstract description 89
- 238000000034 method Methods 0.000 claims abstract description 104
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims abstract description 98
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 238000004393 prognosis Methods 0.000 claims abstract description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 162
- 150000007523 nucleic acids Chemical group 0.000 claims description 86
- 210000004027 cell Anatomy 0.000 claims description 80
- 102000004169 proteins and genes Human genes 0.000 claims description 76
- 230000014509 gene expression Effects 0.000 claims description 73
- 102000039446 nucleic acids Human genes 0.000 claims description 70
- 108020004707 nucleic acids Proteins 0.000 claims description 70
- 108060003951 Immunoglobulin Proteins 0.000 claims description 47
- 102000018358 immunoglobulin Human genes 0.000 claims description 47
- 230000000694 effects Effects 0.000 claims description 42
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 33
- 239000000523 sample Substances 0.000 claims description 29
- 239000003550 marker Substances 0.000 claims description 25
- 101000947193 Homo sapiens C-X-C motif chemokine 3 Proteins 0.000 claims description 24
- 102100036189 C-X-C motif chemokine 3 Human genes 0.000 claims description 22
- 108020004459 Small interfering RNA Proteins 0.000 claims description 22
- 108090000994 Catalytic RNA Proteins 0.000 claims description 16
- 102000053642 Catalytic RNA Human genes 0.000 claims description 16
- 108091092562 ribozyme Proteins 0.000 claims description 16
- 239000003153 chemical reaction reagent Substances 0.000 claims description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 238000001990 intravenous administration Methods 0.000 claims description 14
- 108091034117 Oligonucleotide Proteins 0.000 claims description 13
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 9
- 230000007423 decrease Effects 0.000 claims description 9
- 239000012472 biological sample Substances 0.000 claims description 6
- 230000005754 cellular signaling Effects 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 2
- 229940008228 intravenous immunoglobulins Drugs 0.000 abstract description 118
- 210000004556 brain Anatomy 0.000 abstract description 23
- 201000010099 disease Diseases 0.000 abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
- 208000027866 inflammatory disease Diseases 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 73
- 150000001413 amino acids Chemical class 0.000 description 51
- 235000001014 amino acid Nutrition 0.000 description 39
- 229940024606 amino acid Drugs 0.000 description 39
- 238000002360 preparation method Methods 0.000 description 34
- 238000003556 assay Methods 0.000 description 32
- 108090000765 processed proteins & peptides Chemical group 0.000 description 30
- 239000000090 biomarker Substances 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
- 102000004196 processed proteins & peptides Human genes 0.000 description 26
- 229920001184 polypeptide Chemical group 0.000 description 24
- 241000282414 Homo sapiens Species 0.000 description 22
- 238000009396 hybridization Methods 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- 239000012634 fragment Substances 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- 108010014421 Chemokine CXCL5 Proteins 0.000 description 18
- 102000016948 Chemokine CXCL5 Human genes 0.000 description 18
- 238000003018 immunoassay Methods 0.000 description 18
- 108020004999 messenger RNA Proteins 0.000 description 18
- 238000002560 therapeutic procedure Methods 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- 230000002093 peripheral effect Effects 0.000 description 17
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 16
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 16
- 229940072221 immunoglobulins Drugs 0.000 description 16
- 101000804771 Homo sapiens Cytokine SCM-1 beta Proteins 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 230000003902 lesion Effects 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 14
- 230000001105 regulatory effect Effects 0.000 description 14
- 102100035298 Cytokine SCM-1 beta Human genes 0.000 description 13
- 230000027455 binding Effects 0.000 description 13
- 238000009739 binding Methods 0.000 description 13
- 238000002595 magnetic resonance imaging Methods 0.000 description 13
- 210000004248 oligodendroglia Anatomy 0.000 description 13
- 102000040430 polynucleotide Human genes 0.000 description 13
- 108091033319 polynucleotide Proteins 0.000 description 13
- 239000002157 polynucleotide Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- -1 superoxide anions Chemical class 0.000 description 13
- 101001135402 Homo sapiens Prostaglandin-H2 D-isomerase Proteins 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- VKZRWSNIWNFCIQ-WDSKDSINSA-N (2s)-2-[2-[[(1s)-1,2-dicarboxyethyl]amino]ethylamino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NCCN[C@H](C(O)=O)CC(O)=O VKZRWSNIWNFCIQ-WDSKDSINSA-N 0.000 description 11
- 108020004705 Codon Proteins 0.000 description 11
- 208000017547 Ectodermal dysplasia-syndactyly syndrome Diseases 0.000 description 11
- 238000004422 calculation algorithm Methods 0.000 description 11
- 210000003169 central nervous system Anatomy 0.000 description 11
- 230000000295 complement effect Effects 0.000 description 11
- 238000001514 detection method Methods 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 101000978379 Homo sapiens C-C motif chemokine 13 Proteins 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 210000004408 hybridoma Anatomy 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 102100032616 Caspase-2 Human genes 0.000 description 9
- 102000009410 Chemokine receptor Human genes 0.000 description 9
- 108050000299 Chemokine receptor Proteins 0.000 description 9
- 235000018417 cysteine Nutrition 0.000 description 9
- 239000002502 liposome Substances 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 101000993285 Homo sapiens Collagen alpha-1(III) chain Proteins 0.000 description 8
- 102000002791 Interleukin-8B Receptors Human genes 0.000 description 8
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 102100033279 Prostaglandin-H2 D-isomerase Human genes 0.000 description 8
- 239000012190 activator Substances 0.000 description 8
- 230000000692 anti-sense effect Effects 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 238000002493 microarray Methods 0.000 description 8
- 230000002018 overexpression Effects 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 230000009452 underexpressoin Effects 0.000 description 8
- 108090000552 Caspase-2 Proteins 0.000 description 7
- 208000016192 Demyelinating disease Diseases 0.000 description 7
- 101000762243 Homo sapiens Cadherin-13 Proteins 0.000 description 7
- 101710161469 SH3 domain-binding protein 4 Proteins 0.000 description 7
- 102100028409 SH3 domain-binding protein 4 Human genes 0.000 description 7
- 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 7
- 230000004913 activation Effects 0.000 description 7
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 238000010208 microarray analysis Methods 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 230000000750 progressive effect Effects 0.000 description 7
- 238000003753 real-time PCR Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 102100031611 Collagen alpha-1(III) chain Human genes 0.000 description 6
- 206010012305 Demyelination Diseases 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 101000924488 Homo sapiens Atrial natriuretic peptide receptor 3 Proteins 0.000 description 6
- 101000934870 Homo sapiens Breast cancer type 1 susceptibility protein Proteins 0.000 description 6
- 101001049692 Homo sapiens E3 SUMO-protein ligase EGR2 Proteins 0.000 description 6
- 101000984199 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily A member 4 Proteins 0.000 description 6
- 101000824299 Homo sapiens Protocadherin Fat 2 Proteins 0.000 description 6
- 108091005461 Nucleic proteins Proteins 0.000 description 6
- 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 description 6
- 238000010240 RT-PCR analysis 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
- 239000003446 ligand Substances 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 230000008506 pathogenesis Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 102100024154 Cadherin-13 Human genes 0.000 description 5
- 101000795365 Homo sapiens E3 ubiquitin-protein ligase TRIM58 Proteins 0.000 description 5
- 101001056724 Homo sapiens Intersectin-1 Proteins 0.000 description 5
- 101000966843 Homo sapiens Myotubularin-related protein 7 Proteins 0.000 description 5
- 101001128581 Homo sapiens NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 Proteins 0.000 description 5
- 101000830386 Homo sapiens Neutrophil defensin 3 Proteins 0.000 description 5
- 101000804792 Homo sapiens Protein Wnt-5a Proteins 0.000 description 5
- 101000987488 Homo sapiens Protein pelota homolog Proteins 0.000 description 5
- 101000743825 Homo sapiens Protein zwilch homolog Proteins 0.000 description 5
- 101000834937 Homo sapiens Tomoregulin-1 Proteins 0.000 description 5
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 5
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 102000003815 Interleukin-11 Human genes 0.000 description 5
- 108090000177 Interleukin-11 Proteins 0.000 description 5
- 102100028192 Mitogen-activated protein kinase kinase kinase kinase 2 Human genes 0.000 description 5
- 101710144533 Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 5
- 102000002452 NPR3 Human genes 0.000 description 5
- 108091093037 Peptide nucleic acid Proteins 0.000 description 5
- 102100037914 Pituitary-specific positive transcription factor 1 Human genes 0.000 description 5
- 101710195838 Prostaglandin E2 receptor EP4 subtype Proteins 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 230000009798 acute exacerbation Effects 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 5
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 5
- 230000008499 blood brain barrier function Effects 0.000 description 5
- 210000001218 blood-brain barrier Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 210000002865 immune cell Anatomy 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 229940074383 interleukin-11 Drugs 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 230000010534 mechanism of action Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- 102100025401 Breast cancer type 1 susceptibility protein Human genes 0.000 description 4
- 102100023227 E3 SUMO-protein ligase EGR2 Human genes 0.000 description 4
- 229910052688 Gadolinium Inorganic materials 0.000 description 4
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 4
- 101000867612 Homo sapiens Caspase-2 Proteins 0.000 description 4
- 101000989639 Homo sapiens Major facilitator superfamily domain-containing protein 12 Proteins 0.000 description 4
- 101000634900 Homo sapiens Transcriptional-regulating factor 1 Proteins 0.000 description 4
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- 102100025555 Leukocyte immunoglobulin-like receptor subfamily A member 4 Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 102100022093 Protocadherin Fat 2 Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102100040724 Zinc finger protein 711 Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 210000003050 axon Anatomy 0.000 description 4
- 229940049706 benzodiazepine Drugs 0.000 description 4
- 150000001557 benzodiazepines Chemical class 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 208000025698 brain inflammatory disease Diseases 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 239000003593 chromogenic compound Substances 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 150000001945 cysteines Chemical class 0.000 description 4
- 239000003599 detergent Substances 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 229930182817 methionine Chemical group 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 108010040471 CC Chemokines Proteins 0.000 description 3
- 102000001902 CC Chemokines Human genes 0.000 description 3
- 229940126074 CDK kinase inhibitor Drugs 0.000 description 3
- 108050006947 CXC Chemokine Proteins 0.000 description 3
- 102000019388 CXC chemokine Human genes 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 108010017222 Cyclin-Dependent Kinase Inhibitor p57 Proteins 0.000 description 3
- 102100033269 Cyclin-dependent kinase inhibitor 1C Human genes 0.000 description 3
- 102100034770 Cyclin-dependent kinase inhibitor 3 Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102100029712 E3 ubiquitin-protein ligase TRIM58 Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 101000798387 Homo sapiens Beta-1,3-galactosyltransferase 2 Proteins 0.000 description 3
- 101000945639 Homo sapiens Cyclin-dependent kinase inhibitor 3 Proteins 0.000 description 3
- 101001095308 Homo sapiens Periostin Proteins 0.000 description 3
- 101001117509 Homo sapiens Prostaglandin E2 receptor EP4 subtype Proteins 0.000 description 3
- 101000964741 Homo sapiens Zinc finger protein 711 Proteins 0.000 description 3
- 101000802405 Homo sapiens Zinc finger protein 771 Proteins 0.000 description 3
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 102100025494 Intersectin-1 Human genes 0.000 description 3
- 101710158241 Killer cell immunoglobulin-like receptor 2DS1 Proteins 0.000 description 3
- 102100033631 Killer cell immunoglobulin-like receptor 2DS1 Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 102100040601 Myotubularin-related protein 7 Human genes 0.000 description 3
- 102100032199 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 Human genes 0.000 description 3
- 102100024761 Neutrophil defensin 3 Human genes 0.000 description 3
- 101710163270 Nuclease Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000015439 Phospholipases Human genes 0.000 description 3
- 108010064785 Phospholipases Proteins 0.000 description 3
- 101710129981 Pituitary-specific positive transcription factor 1 Proteins 0.000 description 3
- 102100028485 Protein pelota homolog Human genes 0.000 description 3
- 102100039105 Protein zwilch homolog Human genes 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 241000251131 Sphyrna Species 0.000 description 3
- 102100026159 Tomoregulin-1 Human genes 0.000 description 3
- 102100029446 Transcriptional-regulating factor 1 Human genes 0.000 description 3
- 101710106896 Transmembrane protein 47 Proteins 0.000 description 3
- 102100033526 Transmembrane protein 47 Human genes 0.000 description 3
- 102000014384 Type C Phospholipases Human genes 0.000 description 3
- 108010079194 Type C Phospholipases Proteins 0.000 description 3
- 102000043366 Wnt-5a Human genes 0.000 description 3
- 102100034967 Zinc finger protein 771 Human genes 0.000 description 3
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 3
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 150000001982 diacylglycerols Chemical class 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 238000013537 high throughput screening Methods 0.000 description 3
- 230000003832 immune regulation Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 239000013610 patient sample Substances 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 210000004976 peripheral blood cell Anatomy 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 150000004713 phosphodiesters Chemical class 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000012096 transfection reagent Substances 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 2
- 108050005711 C Chemokine Proteins 0.000 description 2
- 102000017483 C chemokine Human genes 0.000 description 2
- 102000003930 C-Type Lectins Human genes 0.000 description 2
- 108090000342 C-Type Lectins Proteins 0.000 description 2
- 102100028699 C-type lectin domain family 4 member E Human genes 0.000 description 2
- 108010032597 Cohn fraction II Proteins 0.000 description 2
- 108010069502 Collagen Type III Proteins 0.000 description 2
- 102000001187 Collagen Type III Human genes 0.000 description 2
- 108010069514 Cyclic Peptides Proteins 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 208000003164 Diplopia Diseases 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 2
- 108010020382 Hepatocyte Nuclear Factor 1-alpha Proteins 0.000 description 2
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 2
- 101000827785 Homo sapiens Alpha-fetoprotein Proteins 0.000 description 2
- 101000766921 Homo sapiens C-type lectin domain family 4 member E Proteins 0.000 description 2
- 101000944365 Homo sapiens Cyclin-dependent kinase inhibitor 1C Proteins 0.000 description 2
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 2
- 101001010568 Homo sapiens Interleukin-11 Proteins 0.000 description 2
- 101001035935 Homo sapiens Intracellular hyaluronan-binding protein 4 Proteins 0.000 description 2
- 101000945340 Homo sapiens Killer cell immunoglobulin-like receptor 2DS1 Proteins 0.000 description 2
- 101001059990 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101000733743 Homo sapiens Phorbol-12-myristate-13-acetate-induced protein 1 Proteins 0.000 description 2
- 101001096159 Homo sapiens Pituitary-specific positive transcription factor 1 Proteins 0.000 description 2
- 101000632535 Homo sapiens SH3 domain-binding protein 4 Proteins 0.000 description 2
- 101000801314 Homo sapiens Transmembrane protein 47 Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102100039227 Intracellular hyaluronan-binding protein 4 Human genes 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 102100029281 Major facilitator superfamily domain-containing protein 12 Human genes 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 2
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 208000008457 Neurologic Manifestations Diseases 0.000 description 2
- 206010060860 Neurological symptom Diseases 0.000 description 2
- 208000003435 Optic Neuritis Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 101150054854 POU1F1 gene Proteins 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 101710162960 Phorbol-12-myristate-13-acetate-induced protein 1 Proteins 0.000 description 2
- 102100033716 Phorbol-12-myristate-13-acetate-induced protein 1 Human genes 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 108091030071 RNAI Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 108010046334 Urease Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 101710182141 Zinc finger protein 711 Proteins 0.000 description 2
- 101710182376 Zinc finger protein 771 Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000030570 cellular localization Effects 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000003210 demyelinating effect Effects 0.000 description 2
- JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical compound CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000003094 enzyme-multiplied immunoassay technique Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000002075 inversion recovery Methods 0.000 description 2
- XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 230000023105 myelination Effects 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 238000004848 nephelometry Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000000535 oligodendrocyte precursor cell Anatomy 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 101150056399 slc20a1 gene Proteins 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000011272 standard treatment Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000011179 visual inspection Methods 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
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- 108010063503 Actinin Proteins 0.000 description 1
- 102000010825 Actinin Human genes 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102100032964 Alpha-actinin-2 Human genes 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100032440 Beta-1,3-galactosyltransferase 2 Human genes 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 1
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 1
- 102000014818 Cadherin-13 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101800001318 Capsid protein VP4 Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102100024931 Caspase-14 Human genes 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
- 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 230000005971 DNA damage repair Effects 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- XULFJDKZVHTRLG-JDVCJPALSA-N DOSPA trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)CCNC(=O)C(CCCNCCCN)NCCCN)OCCCCCCCC\C=C/CCCCCCCC XULFJDKZVHTRLG-JDVCJPALSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 108010089760 Electron Transport Complex I Proteins 0.000 description 1
- 102000008013 Electron Transport Complex I Human genes 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 108010093099 Endoribonucleases Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010088842 Fibrinolysin Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 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
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108010066705 H-cadherin Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100030650 Histone H2B type 1-H Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000797275 Homo sapiens Alpha-actinin-2 Proteins 0.000 description 1
- 101000761467 Homo sapiens Caspase-14 Proteins 0.000 description 1
- 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 1
- 101001084676 Homo sapiens Histone H2B type 1-H Proteins 0.000 description 1
- 101000804764 Homo sapiens Lymphotactin Proteins 0.000 description 1
- 101000940817 Homo sapiens Lysophospholipid acyltransferase LPCAT4 Proteins 0.000 description 1
- 101000918983 Homo sapiens Neutrophil defensin 1 Proteins 0.000 description 1
- 101000613969 Homo sapiens Origin recognition complex subunit 1 Proteins 0.000 description 1
- 101001120706 Homo sapiens Outer dense fiber protein 2 Proteins 0.000 description 1
- 101001088128 Homo sapiens Ropporin-1B Proteins 0.000 description 1
- 101000766253 Homo sapiens TLR4 interactor with leucine rich repeats Proteins 0.000 description 1
- 101000634866 Homo sapiens TRAF-type zinc finger domain-containing protein 1 Proteins 0.000 description 1
- 101000976250 Homo sapiens Zinc finger protein 804A Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical group OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical group C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Chemical group CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102100031741 Lysophospholipid acyltransferase LPCAT4 Human genes 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 101000824301 Mus musculus Protocadherin Fat 2 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 101150066297 NPR3 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100029494 Neutrophil defensin 1 Human genes 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 102000016304 Origin Recognition Complex Human genes 0.000 description 1
- 108010067244 Origin Recognition Complex Proteins 0.000 description 1
- 102100040591 Origin recognition complex subunit 1 Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100026069 Outer dense fiber protein 2 Human genes 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 208000032860 Partial vision loss Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 102100037765 Periostin Human genes 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 201000007902 Primary cutaneous amyloidosis Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 1
- 102100032225 Ropporin-1B Human genes 0.000 description 1
- 102000000395 SH3 domains Human genes 0.000 description 1
- 108050008861 SH3 domains Proteins 0.000 description 1
- 108091079435 SIS family Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102100026308 TLR4 interactor with leucine rich repeats Human genes 0.000 description 1
- 102100029451 TRAF-type zinc finger domain-containing protein 1 Human genes 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 101710130537 Transcriptional-regulating factor 1 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
- 101710100170 Unknown protein Proteins 0.000 description 1
- 102000008790 VE-cadherin Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000001790 Welch's t-test Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 101710180877 Zinc finger protein 6 Proteins 0.000 description 1
- 102100023875 Zinc finger protein 804A Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- 230000030120 acrosome reaction Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 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
- 125000003277 amino group Chemical group 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000007844 axonal damage Effects 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000005821 brain abnormality Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 108010018828 cadherin 5 Proteins 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 239000012504 chromatography matrix Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000022371 chronic pain syndrome Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000003935 denaturing gradient gel electrophoresis Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 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
- 230000009266 disease activity Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000029444 double vision Diseases 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 1
- 229940009600 gammagard Drugs 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 229960003776 glatiramer acetate Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000021158 homophilic cell adhesion Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 108010079515 intersectin 1 Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940124625 intravenous corticosteroids Drugs 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000027291 mitotic cell cycle Effects 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000010369 molecular cloning 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
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 230000010004 neural pathway Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000007826 nucleic acid assay Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 238000002966 oligonucleotide array Methods 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 238000009928 pasteurization Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 108010055837 phosphocarrier protein HPr Proteins 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940096015 polygam s/d Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000035456 regulation of T cell proliferation Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000005067 remediation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 230000012488 skeletal system development Effects 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 230000003238 somatosensory effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 230000021595 spermatogenesis Effects 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- CCEKAJIANROZEO-UHFFFAOYSA-N sulfluramid Chemical group CCNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F CCEKAJIANROZEO-UHFFFAOYSA-N 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 101150041456 zwilch gene Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- General Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Transplantation (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2013276991A AU2013276991C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276992A AU2013276992C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276994A AU2013276994C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276993A AU2013276993B9 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US95561007P | 2007-08-13 | 2007-08-13 | |
| US60/955,610 | 2007-08-13 | ||
| PCT/EP2008/006608 WO2009021708A2 (en) | 2007-08-13 | 2008-08-11 | Ivig modulation of chemokines for treatment of multiple sclerosis, alzheimer's disease, and parkinson's disease |
Related Child Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013276994A Division AU2013276994C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276992A Division AU2013276992C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276991A Division AU2013276991C1 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
| AU2013276993A Division AU2013276993B9 (en) | 2007-08-13 | 2013-12-24 | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008286361A1 AU2008286361A1 (en) | 2009-02-19 |
| AU2008286361B2 true AU2008286361B2 (en) | 2013-09-26 |
Family
ID=40259157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008286361A Ceased AU2008286361B2 (en) | 2007-08-13 | 2008-08-11 | IVIG modulation of chemokines for treatment of multiple sclerosis, Alzheimer's disease, and Parkinson's disease |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7968293B2 (enExample) |
| EP (5) | EP2522753B1 (enExample) |
| JP (1) | JP5555626B2 (enExample) |
| AU (1) | AU2008286361B2 (enExample) |
| CA (1) | CA2695972A1 (enExample) |
| ES (5) | ES2477271T3 (enExample) |
| WO (1) | WO2009021708A2 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090280114A1 (en) * | 2002-04-12 | 2009-11-12 | Ramot At Tel Aviv University Ltd. | Prevention of brain inflammation as a result of induced autoimmune response |
| WO2010112034A2 (en) * | 2009-04-02 | 2010-10-07 | Aarhus Universitet | Compositions and methods for treatment and diagnosis of synucleinopathies |
| BRPI1012082B1 (pt) | 2009-05-27 | 2022-08-16 | Takeda Pharmaceutical Company Limited | Método para preparar uma composição de igg concentrada a partir de plasma |
| SG184820A1 (en) * | 2010-04-13 | 2012-11-29 | Baxter Int | Use of ventricular enlargement rate in intravenous immunoglobulin treatment of alzheimer's disease |
| US8796430B2 (en) | 2010-05-26 | 2014-08-05 | Baxter International Inc. | Method to produce an immunoglobulin preparation with improved yield |
| AU2010202125B1 (en) | 2010-05-26 | 2010-09-02 | Takeda Pharmaceutical Company Limited | A method to produce an immunoglobulin preparation with improved yield |
| WO2011150284A2 (en) | 2010-05-26 | 2011-12-01 | Baxter International Inc. | Removal of serine proteases by treatment with finely divided silicon dioxide |
| EP2477032A1 (en) | 2011-01-18 | 2012-07-18 | Baxter International Inc | Measurement of anti-amyloid antibodies in human blood |
| KR20130139153A (ko) | 2011-01-18 | 2013-12-20 | 백스터 인터내셔널 인코포레이티드 | 인간 혈액 중 항-베타 아밀로이드 항체의 측정 |
| US20120251524A1 (en) * | 2011-04-01 | 2012-10-04 | Baxter Healthcare S.A. | Use of cytokine levels in intravenous immunoglobulin treatment of alzheimer's disease |
| PT2791675T (pt) | 2011-12-13 | 2018-07-27 | Baxalta Inc | Medição de autoanticorpos em condições de baixa condutividade |
| WO2014149067A1 (en) | 2013-03-15 | 2014-09-25 | Momenta Pharmaceuticals, Inc. | Methods related to ctla4-fc fusion proteins |
| US10464996B2 (en) | 2013-05-13 | 2019-11-05 | Momenta Pharmaceuticals, Inc. | Methods for the treatment of neurodegeneration |
| US20160257754A1 (en) | 2013-10-16 | 2016-09-08 | Momenta Pharmaceuticals Inc. | Sialylated glycoproteins |
| WO2017070589A1 (en) * | 2015-10-22 | 2017-04-27 | Duke University | Methods and compositions for the diagnosis and treatment of central nervous system autoimmune diseases |
| EP3920887B1 (en) * | 2019-02-04 | 2024-08-14 | The Regents of the University of California | A phosphatidylinositol-glycan-specific phospholipase d1 (gpld1) polypeptide for use in a method of treating or preventing age-related cognitive dysfunction |
| CA3173539A1 (en) | 2020-03-31 | 2021-10-07 | Takeda Pharmaceutical Company Limited | A method to produce an immunoglobulin preparation from c-1 inhibitor depleted plasma |
| EP4490042A1 (en) | 2022-03-08 | 2025-01-15 | Equashield Medical Ltd. | Fluid transfer station in a robotic pharmaceutical preparation system |
| CN116790745A (zh) * | 2023-07-03 | 2023-09-22 | 复旦大学 | 阿尔茨海默病临床前期疾病转化的标志物及其筛选方法 |
| WO2025068923A2 (en) | 2023-09-26 | 2025-04-03 | Takeda Pharmaceutical Company Limited | IMMUNOGLOBULIN FORMULATIONS DEPLETED IN IgA |
| CN119020481A (zh) * | 2024-08-29 | 2024-11-26 | 河络新图生物科技(上海)有限公司 | 检测xcl2基因表达的物质在制备检测帕金森病产品中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002059604A2 (en) * | 2001-01-26 | 2002-08-01 | Oxford Glycosciences (Uk) Ltd | Diagnosis and treatment of multiple sclerosis |
Family Cites Families (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT376367B (de) | 1983-03-16 | 1984-11-12 | Immuno Ag | Verfahren zur herstellung von therapeutisch verabreichbaren, in endbehaeltern abgefuellten plasmaderivaten |
| DK166763C (da) | 1983-03-16 | 1993-07-12 | Immuno Ag | Immunoglobulin-g-holdig fraktion |
| EP0124506B1 (de) | 1983-05-02 | 1988-08-17 | IMMUNO Aktiengesellschaft für chemisch-medizinische Produkte | Verfahren zur Inaktivierung von vermehrungsfähigen Krankheitserregern |
| AT389815B (de) | 1984-03-09 | 1990-02-12 | Immuno Ag | Verfahren zur inaktivierung von vermehrungsfaehigen filtrierbaren krankheitserregern in blutprodukten |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| AT390560B (de) | 1986-05-30 | 1990-05-25 | Immuno Ag | Verfahren zur inaktivierung von vermehrungsfaehigen filtrierbaren krankheitserregern |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5010175A (en) | 1988-05-02 | 1991-04-23 | The Regents Of The University Of California | General method for producing and selecting peptides with specific properties |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| JP2871709B2 (ja) | 1988-11-21 | 1999-03-17 | 住友製薬株式会社 | 免疫グロブリンｇ結合活性を有する新規な蛋白質プロテインｈ、該蛋白質をコードする遺伝子及び該蛋白質の製造法 |
| US5177194A (en) | 1990-02-01 | 1993-01-05 | Baxter International, Inc. | Process for purifying immune serum globulins |
| IE66205B1 (en) | 1990-06-14 | 1995-12-13 | Paul A Bartlett | Polypeptide analogs |
| US5650489A (en) | 1990-07-02 | 1997-07-22 | The Arizona Board Of Regents | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| AT402891B (de) | 1991-06-20 | 1997-09-25 | Immuno Ag | Verfahren zur herstellung eines inaktivierten blutproduktes |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5885527A (en) | 1992-05-21 | 1999-03-23 | Biosite Diagnostics, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membrances |
| US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
| WO1994013329A1 (de) | 1992-12-16 | 1994-06-23 | Immuno Aktiengesellschaft | Verfahren zur herstellung eines virussicheren biologischen präparates |
| HRP940645A2 (en) | 1993-10-06 | 1996-12-31 | Immuno Ag | Process for virus deactivation in the presence of polyalkylene glycol and the pharmaceutical preparation thus obtained |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5593853A (en) | 1994-02-09 | 1997-01-14 | Martek Corporation | Generation and screening of synthetic drug libraries |
| US5539083A (en) | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
| US6447796B1 (en) | 1994-05-16 | 2002-09-10 | The United States Of America As Represented By The Secretary Of The Army | Sustained release hydrophobic bioactive PLGA microspheres |
| US5525735A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies Nv | Methods for synthesizing diverse collections of pyrrolidine compounds |
| US5549974A (en) | 1994-06-23 | 1996-08-27 | Affymax Technologies Nv | Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof |
| US5569588A (en) | 1995-08-09 | 1996-10-29 | The Regents Of The University Of California | Methods for drug screening |
| US20020114802A1 (en) | 1998-02-10 | 2002-08-22 | Tjellstrom Bo Arthur Einar | Oral immunoglobulin treatment for inflammatory bowel disease |
| EP1159441B8 (en) | 1999-03-10 | 2008-10-29 | Marie Curie Cancer Care | Delivery of nucleic acids and proteins to cells |
| AU2001273661A1 (en) | 2000-06-30 | 2002-01-14 | Duke University | Methods of screening for alzheimer's disease |
| US20020098182A1 (en) | 2000-09-28 | 2002-07-25 | Richard Weisbart | Treatment of immune-mediated diseases by oral administration of plasma fractions enriched in immunoglobulin G |
| US20020130430A1 (en) | 2000-12-29 | 2002-09-19 | Castor Trevor Percival | Methods for making polymer microspheres/nanospheres and encapsulating therapeutic proteins and other products |
| US6905827B2 (en) * | 2001-06-08 | 2005-06-14 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases |
| WO2003028668A2 (en) | 2001-10-04 | 2003-04-10 | Protein Therapeutics, Inc. | Gammaglobulin treatment of immune disorders |
| US7060498B1 (en) | 2001-11-28 | 2006-06-13 | Genta Salus Llc | Polycationic water soluble copolymer and method for transferring polyanionic macromolecules across biological barriers |
| US7442512B2 (en) * | 2001-11-30 | 2008-10-28 | Chemocentryx, Inc. | Compositions and methods for detecting and treating diseases and conditions related to chemokine receptors |
| US7141540B2 (en) | 2001-11-30 | 2006-11-28 | Genta Salus Llc | Cyclodextrin grafted biocompatible amphilphilic polymer and methods of preparation and use thereof |
| US20050222064A1 (en) | 2002-02-20 | 2005-10-06 | Sirna Therapeutics, Inc. | Polycationic compositions for cellular delivery of polynucleotides |
| AU2003214604A1 (en) * | 2002-03-21 | 2003-10-08 | Hadasit Medical Research Services And Development Ltd. | Peripheral blood cell markers useful for diagnosing multiple sclerosis and methods and kits utilizing same |
| US20040014109A1 (en) | 2002-05-23 | 2004-01-22 | Pericak-Vance Margaret A. | Methods and genes associated with screening assays for age at onset and common neurodegenerative diseases |
| AU2003251962A1 (en) | 2002-07-08 | 2004-01-23 | Duke University | Screening for alzheimer's disease |
| US20040204377A1 (en) | 2002-11-26 | 2004-10-14 | University Of Massachusetts | Delivery of siRNAs |
| WO2005027733A2 (en) * | 2003-09-18 | 2005-03-31 | Ppd Biomarker Discovery Sciences, Llc | Biological markers for diagnosing multiple sclerosis |
| WO2005060697A2 (en) | 2003-12-19 | 2005-07-07 | Chiron Corporation | Cell transfecting formulations of small interfering rna, related compositions and methods of making and use |
| JP2007525211A (ja) * | 2004-01-19 | 2007-09-06 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | パーキンソン病の診断検査 |
| EP1773998A2 (en) | 2004-04-20 | 2007-04-18 | Nastech Pharmaceutical Company Inc. | Methods and compositions for enhancing delivery of double-stranded rna or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells |
| US7514530B2 (en) | 2004-04-26 | 2009-04-07 | Centre National De La Recherche Scientifique | Peptide carrier for delivering siRNA into mammalian cells |
| WO2006077126A2 (en) | 2005-01-19 | 2006-07-27 | Bayer Schering Pharma Aktiengesellschaft | Cx3cr1 as a marker which correlates with both disease and disease activity in multiple sclerosis patients |
| WO2006101925A2 (en) * | 2005-03-16 | 2006-09-28 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors |
| US20080045582A1 (en) * | 2006-05-15 | 2008-02-21 | Issam Zineh | ENA-78 Gene Polymorphisms and Protein Concentrations as Diagnostic and Prognostic Tools |
| DE602007013615D1 (de) * | 2006-12-29 | 2011-05-12 | Tel Hashomer Medical Res Infrastructure & Services Ltd | Verfahren und kits zur diagnose von multipler sklerose bei wahrscheinlichen multiple-sklerose-patienten |
| JO3421B1 (ar) | 2011-06-20 | 2019-10-20 | H Lundbeck As | طريقة لإعطاء 1-((1ار.3س)-6-كلورو-3-فينيل-اندان-1-ايل)-1.2.2-ترايميثيل- بيبيرازين واملاجها لمعالجة انفصام الشخصية |
-
2008
- 2008-08-11 EP EP12179739.3A patent/EP2522753B1/en active Active
- 2008-08-11 JP JP2010520478A patent/JP5555626B2/ja not_active Expired - Fee Related
- 2008-08-11 WO PCT/EP2008/006608 patent/WO2009021708A2/en not_active Ceased
- 2008-08-11 ES ES12179736.9T patent/ES2477271T3/es active Active
- 2008-08-11 CA CA2695972A patent/CA2695972A1/en not_active Abandoned
- 2008-08-11 ES ES12179739.3T patent/ES2477292T3/es active Active
- 2008-08-11 ES ES12179740.1T patent/ES2477293T3/es active Active
- 2008-08-11 EP EP12179740.1A patent/EP2522754B1/en active Active
- 2008-08-11 ES ES08785488T patent/ES2416719T3/es active Active
- 2008-08-11 AU AU2008286361A patent/AU2008286361B2/en not_active Ceased
- 2008-08-11 ES ES12179743.5T patent/ES2477294T3/es active Active
- 2008-08-11 EP EP12179743.5A patent/EP2522755B1/en active Active
- 2008-08-11 EP EP12179736.9A patent/EP2522752B1/en active Active
- 2008-08-11 EP EP08785488A patent/EP2191014B1/en active Active
- 2008-08-11 US US12/189,367 patent/US7968293B2/en not_active Expired - Fee Related
-
2011
- 2011-02-11 US US13/026,053 patent/US20110177094A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002059604A2 (en) * | 2001-01-26 | 2002-08-01 | Oxford Glycosciences (Uk) Ltd | Diagnosis and treatment of multiple sclerosis |
Also Published As
| Publication number | Publication date |
|---|---|
| US20090148463A1 (en) | 2009-06-11 |
| US7968293B2 (en) | 2011-06-28 |
| EP2522754B1 (en) | 2014-04-02 |
| ES2416719T3 (es) | 2013-08-02 |
| ES2477293T3 (es) | 2014-07-16 |
| CA2695972A1 (en) | 2009-02-19 |
| ES2477271T3 (es) | 2014-07-16 |
| EP2522755A1 (en) | 2012-11-14 |
| US20110177094A1 (en) | 2011-07-21 |
| AU2008286361A1 (en) | 2009-02-19 |
| ES2477294T3 (es) | 2014-07-16 |
| JP2010535825A (ja) | 2010-11-25 |
| EP2522754A1 (en) | 2012-11-14 |
| WO2009021708A2 (en) | 2009-02-19 |
| EP2522755B1 (en) | 2014-04-02 |
| EP2522753A1 (en) | 2012-11-14 |
| EP2522752A1 (en) | 2012-11-14 |
| JP5555626B2 (ja) | 2014-07-23 |
| WO2009021708A3 (en) | 2009-05-28 |
| EP2522752B1 (en) | 2014-04-02 |
| EP2191014A2 (en) | 2010-06-02 |
| EP2191014B1 (en) | 2013-04-03 |
| EP2522753B1 (en) | 2014-04-02 |
| ES2477292T3 (es) | 2014-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008286361B2 (en) | IVIG modulation of chemokines for treatment of multiple sclerosis, Alzheimer's disease, and Parkinson's disease | |
| US10889865B2 (en) | Thyroid tumors identified | |
| CN109863251B (zh) | 对肺鳞状细胞癌亚型分型的方法 | |
| ES2374954T3 (es) | Variaciones genéticas asociadas con tumores. | |
| AU2016295347A1 (en) | Gene signature for immune therapies in cancer | |
| AU2018290809B2 (en) | Biomarkers for the diagnosis and treatment of fibrotic lung disease | |
| KR20100095564A (ko) | 항-ｃｄ４０ 항체를 사용한 치료에 대한 ｂ-세포 림프종의 반응성 평가를 위한 방법 및 조성물 | |
| CA2430981A1 (en) | Gene expression profiling of primary breast carcinomas using arrays of candidate genes | |
| KR20120047334A (ko) | 자궁내막암 마커 | |
| CA3067730A1 (en) | Methods for detection of plasma cell dyscrasia | |
| CN101111768A (zh) | 肺癌预后 | |
| CN101778954A (zh) | Egfr抑制剂治疗的预测性标记物 | |
| AU2013276991B2 (en) | IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease | |
| IL270787B2 (en) | Melanoma detection methods | |
| CA2587863A1 (en) | Genes associated with colorectal cancer | |
| KR20120093956A (ko) | 종양 분류를 위한 ｉｒ-ａ 및 ｉｒ-ｂ의 정량 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| PC | Assignment registered |
Owner name: BAXALTA INCORPORATED; BAXALTA GMBH Free format text: FORMER OWNER WAS: BAXTER INTERNATIONAL INC.; BAXTER HEALTHCARE S.A. |
|
| PC | Assignment registered |
Owner name: TAKEDA PHARMACEUTICAL COMPANY LIMITED Free format text: FORMER OWNER(S): BAXALTA GMBH; BAXALTA INCORPORATED |
|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |