CN116966293A - 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 - Google Patents
脑信号蛋白-4d结合分子治疗神经变性疾病的用途 Download PDFInfo
- Publication number
- CN116966293A CN116966293A CN202310282388.8A CN202310282388A CN116966293A CN 116966293 A CN116966293 A CN 116966293A CN 202310282388 A CN202310282388 A CN 202310282388A CN 116966293 A CN116966293 A CN 116966293A
- Authority
- CN
- China
- Prior art keywords
- sema4d
- antibody
- disease
- binding
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000027455 binding Effects 0.000 title claims abstract description 223
- 108010056102 CD100 antigen Proteins 0.000 title claims abstract description 214
- 102100027744 Semaphorin-4D Human genes 0.000 title claims abstract description 212
- 230000004770 neurodegeneration Effects 0.000 title abstract description 72
- 208000015122 neurodegenerative disease Diseases 0.000 title abstract description 72
- 238000011282 treatment Methods 0.000 title description 65
- 102100034384 Plexin-B1 Human genes 0.000 claims abstract description 44
- 101710100559 Plexin-B1 Proteins 0.000 claims abstract description 43
- 101710100551 Plexin-B2 Proteins 0.000 claims abstract description 31
- 102100034383 Plexin-B2 Human genes 0.000 claims abstract description 31
- 210000001130 astrocyte Anatomy 0.000 claims description 113
- 239000000427 antigen Substances 0.000 claims description 107
- 108091007433 antigens Proteins 0.000 claims description 107
- 102000036639 antigens Human genes 0.000 claims description 107
- 239000012634 fragment Substances 0.000 claims description 87
- 241000282414 Homo sapiens Species 0.000 claims description 76
- 208000024827 Alzheimer disease Diseases 0.000 claims description 58
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 39
- 230000011664 signaling Effects 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 230000001404 mediated effect Effects 0.000 claims description 14
- 230000003993 interaction Effects 0.000 claims description 13
- 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 claims description 11
- 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 claims description 11
- 230000000946 synaptic effect Effects 0.000 claims description 8
- 230000016273 neuron death Effects 0.000 claims description 2
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 149
- 208000024891 symptom Diseases 0.000 abstract description 52
- 241000699670 Mus sp. Species 0.000 description 104
- 108090000765 processed proteins & peptides Proteins 0.000 description 56
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 52
- 102000004196 processed proteins & peptides Human genes 0.000 description 51
- 229920001184 polypeptide Polymers 0.000 description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 47
- 201000010099 disease Diseases 0.000 description 46
- 235000001014 amino acid Nutrition 0.000 description 45
- 239000003814 drug Substances 0.000 description 44
- 108020003175 receptors Proteins 0.000 description 44
- 102000005962 receptors Human genes 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 39
- 230000000694 effects Effects 0.000 description 39
- 230000008569 process Effects 0.000 description 34
- 230000004913 activation Effects 0.000 description 32
- 108060003951 Immunoglobulin Proteins 0.000 description 29
- 102000018358 immunoglobulin Human genes 0.000 description 29
- 208000023105 Huntington disease Diseases 0.000 description 28
- 229940024606 amino acid Drugs 0.000 description 28
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 27
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 27
- 150000001413 amino acids Chemical class 0.000 description 27
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 27
- 210000004556 brain Anatomy 0.000 description 26
- 229940124597 therapeutic agent Drugs 0.000 description 26
- 239000000203 mixture Substances 0.000 description 22
- 238000006467 substitution reaction Methods 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- 210000003169 central nervous system Anatomy 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 18
- 230000008499 blood brain barrier function Effects 0.000 description 18
- 210000001218 blood-brain barrier Anatomy 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 241000700159 Rattus Species 0.000 description 17
- 208000010877 cognitive disease Diseases 0.000 description 17
- 210000002569 neuron Anatomy 0.000 description 17
- 201000011240 Frontotemporal dementia Diseases 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 16
- 230000033001 locomotion Effects 0.000 description 16
- 239000003550 marker Substances 0.000 description 16
- 230000035772 mutation Effects 0.000 description 16
- 241001529936 Murinae Species 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 238000002560 therapeutic procedure Methods 0.000 description 15
- 230000006378 damage Effects 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 238000010186 staining Methods 0.000 description 14
- 230000007529 anxiety like behavior Effects 0.000 description 13
- 238000010172 mouse model Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 108010036280 Aquaporin 4 Proteins 0.000 description 12
- 102000012002 Aquaporin 4 Human genes 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 12
- 125000000539 amino acid group Chemical group 0.000 description 11
- 210000003719 b-lymphocyte Anatomy 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 208000015114 central nervous system disease Diseases 0.000 description 11
- 230000036541 health Effects 0.000 description 11
- 230000006886 spatial memory Effects 0.000 description 11
- 101150073415 Aqp4 gene Proteins 0.000 description 10
- 208000018737 Parkinson disease Diseases 0.000 description 10
- 102100038170 Vesicular inhibitory amino acid transporter Human genes 0.000 description 10
- 208000027418 Wounds and injury Diseases 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000002889 endothelial cell Anatomy 0.000 description 10
- 208000014674 injury Diseases 0.000 description 10
- 230000003902 lesion Effects 0.000 description 10
- 239000002243 precursor Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 10
- 108010030503 vesicular GABA transporter Proteins 0.000 description 10
- 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 9
- 206010003591 Ataxia Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 102000002022 plexin Human genes 0.000 description 9
- 108050009312 plexin Proteins 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 108010085238 Actins Proteins 0.000 description 8
- 102000007469 Actins Human genes 0.000 description 8
- 208000028698 Cognitive impairment Diseases 0.000 description 8
- 208000016192 Demyelinating disease Diseases 0.000 description 8
- 201000010374 Down Syndrome Diseases 0.000 description 8
- 101710151321 Melanostatin Proteins 0.000 description 8
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 8
- 102400000064 Neuropeptide Y Human genes 0.000 description 8
- 208000011235 central nervous system lupus Diseases 0.000 description 8
- 230000007850 degeneration Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000002518 glial effect Effects 0.000 description 8
- 210000001320 hippocampus Anatomy 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 208000027061 mild cognitive impairment Diseases 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 8
- 230000001737 promoting effect Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 description 7
- -1 IgM Chemical compound 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 210000004443 dendritic cell Anatomy 0.000 description 7
- 210000001947 dentate gyrus Anatomy 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000835 fiber Substances 0.000 description 7
- 238000002991 immunohistochemical analysis Methods 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000000670 limiting effect Effects 0.000 description 7
- 230000004807 localization Effects 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 210000000278 spinal cord Anatomy 0.000 description 7
- 206010012305 Demyelination Diseases 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 206010061296 Motor dysfunction Diseases 0.000 description 6
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000283984 Rodentia Species 0.000 description 6
- 210000001056 activated astrocyte Anatomy 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 230000006907 apoptotic process Effects 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 210000005210 lymphoid organ Anatomy 0.000 description 6
- 210000000274 microglia Anatomy 0.000 description 6
- 238000010369 molecular cloning Methods 0.000 description 6
- 210000004498 neuroglial cell Anatomy 0.000 description 6
- 230000002314 neuroinflammatory effect Effects 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 210000000225 synapse Anatomy 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 230000003827 upregulation Effects 0.000 description 6
- 208000019901 Anxiety disease Diseases 0.000 description 5
- 101150013553 CD40 gene Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 108050003978 Semaphorin Proteins 0.000 description 5
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 5
- 230000036506 anxiety Effects 0.000 description 5
- 230000003140 astrocytic effect Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000005013 brain tissue Anatomy 0.000 description 5
- 210000003855 cell nucleus Anatomy 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000001054 cortical effect Effects 0.000 description 5
- 230000009260 cross reactivity Effects 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 238000002703 mutagenesis Methods 0.000 description 5
- 231100000350 mutagenesis Toxicity 0.000 description 5
- 210000004248 oligodendroglia Anatomy 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 4
- 101150053137 AIF1 gene Proteins 0.000 description 4
- 108091006151 Glutamate transporters Proteins 0.000 description 4
- 102000034575 Glutamate transporters Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 101000650817 Homo sapiens Semaphorin-4D Proteins 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 101100310048 Mus musculus Sema4d gene Proteins 0.000 description 4
- 108010057466 NF-kappa B Proteins 0.000 description 4
- 102000003945 NF-kappa B Human genes 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 102000014105 Semaphorin Human genes 0.000 description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 description 4
- 230000000890 antigenic effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000003376 axonal effect Effects 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000008482 dysregulation Effects 0.000 description 4
- 238000013401 experimental design Methods 0.000 description 4
- 230000003371 gabaergic effect Effects 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 230000016784 immunoglobulin production Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 210000000535 oligodendrocyte precursor cell Anatomy 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 230000010287 polarization Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 4
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 229960000553 somatostatin Drugs 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 230000002381 testicular Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- 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 3
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 3
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 3
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 3
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 3
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 3
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 3
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 3
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 3
- 102000005157 Somatostatin Human genes 0.000 description 3
- 108010056088 Somatostatin Proteins 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000020411 cell activation Effects 0.000 description 3
- 230000012292 cell migration Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 210000005220 cytoplasmic tail Anatomy 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000001934 delay Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 3
- 229960005542 ethidium bromide Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000004088 microvessel Anatomy 0.000 description 3
- 230000000626 neurodegenerative effect Effects 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 238000012346 open field test Methods 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 230000004797 therapeutic response Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 230000001228 trophic effect Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 230000007730 Akt signaling Effects 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 102000010637 Aquaporins Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 230000009165 GABAergic signaling Effects 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 206010019851 Hepatotoxicity Diseases 0.000 description 2
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 2
- 102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 2
- 238000004497 NIR spectroscopy Methods 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000003435 Optic Neuritis Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 240000007643 Phytolacca americana Species 0.000 description 2
- 235000009074 Phytolacca americana Nutrition 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 101150111584 RHOA gene Proteins 0.000 description 2
- 208000032023 Signs and Symptoms Diseases 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 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
- 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 description 2
- 101710128901 Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241001416177 Vicugna pacos Species 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000037875 astrocytosis Diseases 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000002457 bidirectional effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000006041 cell recruitment Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000000877 corpus callosum Anatomy 0.000 description 2
- 210000003618 cortical neuron Anatomy 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000004041 dendritic cell maturation Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 208000015756 familial Alzheimer disease Diseases 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 230000004914 glial activation Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 230000001378 hepatocarcinogenic effect Effects 0.000 description 2
- 231100000334 hepatotoxic Toxicity 0.000 description 2
- 230000003082 hepatotoxic effect Effects 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 230000007686 hepatotoxicity Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000011005 laboratory method Methods 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 230000014950 maintenance of blood-brain barrier Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 230000017511 neuron migration Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 238000012014 optical coherence tomography Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000010845 search algorithm Methods 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000007470 synaptic degeneration Effects 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 238000007492 two-way ANOVA Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000006888 Agnosia Diseases 0.000 description 1
- 241001047040 Agnosia Species 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 206010051288 Central nervous system inflammation Diseases 0.000 description 1
- 102000034573 Channels Human genes 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 229930195711 D-Serine Natural products 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101100518002 Danio rerio nkx2.2a gene Proteins 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 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
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 102100027886 Homeobox protein Nkx-2.2 Human genes 0.000 description 1
- 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101100460496 Homo sapiens NKX2-2 gene Proteins 0.000 description 1
- 101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 description 1
- 101001067174 Homo sapiens Plexin-B1 Proteins 0.000 description 1
- 101000686246 Homo sapiens Ras-related protein R-Ras Proteins 0.000 description 1
- 101000650814 Homo sapiens Semaphorin-4C Proteins 0.000 description 1
- 101150043003 Htt gene Proteins 0.000 description 1
- 102000016252 Huntingtin Human genes 0.000 description 1
- 108050004784 Huntingtin Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 101100042271 Mus musculus Sema3b gene Proteins 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 101150100944 Nos2 gene Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 101710086070 Plexin-B Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 102100024683 Ras-related protein R-Ras Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 241000271569 Rhea Species 0.000 description 1
- 102100039640 Rho-related GTP-binding protein RhoE Human genes 0.000 description 1
- 108050007494 Rho-related GTP-binding protein RhoE Proteins 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 102100027745 Semaphorin-4C Human genes 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 102000004402 Syntrophin Human genes 0.000 description 1
- 108090000916 Syntrophin Proteins 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000282458 Ursus sp. Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940024548 aluminum oxide Drugs 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006400 anxiety behaviour Effects 0.000 description 1
- 230000010397 anxiety-related behavior Effects 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 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
- 238000003556 assay Methods 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000004009 axon guidance Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 208000025698 brain inflammatory disease Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000028956 calcium-mediated signaling Effects 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 125000001314 canonical amino-acid group Chemical group 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 208000004209 confusion Diseases 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 206010013395 disorientation Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000007277 glial cell activation Effects 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000000020 growth cone Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- KFHHGNBIPJDZPH-UHFFFAOYSA-D pentamagnesium [oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O KFHHGNBIPJDZPH-UHFFFAOYSA-D 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 108010040003 polyglutamine Proteins 0.000 description 1
- 229920000155 polyglutamine Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000007342 reactive astrogliosis Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 108010084272 syntrophin alpha1 Proteins 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000622 toxicogenomics Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000001296 transplacental effect Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361893814P | 2013-10-21 | 2013-10-21 | |
| US61/893,814 | 2013-10-21 | ||
| US201461979384P | 2014-04-14 | 2014-04-14 | |
| US61/979,384 | 2014-04-14 | ||
| US201462012805P | 2014-06-16 | 2014-06-16 | |
| US62/012,805 | 2014-06-16 | ||
| PCT/US2014/061592 WO2015061330A1 (en) | 2013-10-21 | 2014-10-21 | Use of semaphorin-4d binding molecules for treating neurodegenerative disorders |
| CN201480070232.2A CN106029093B (zh) | 2013-10-21 | 2014-10-21 | 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480070232.2A Division CN106029093B (zh) | 2013-10-21 | 2014-10-21 | 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116966293A true CN116966293A (zh) | 2023-10-31 |
Family
ID=52826380
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310282388.8A Pending CN116966293A (zh) | 2013-10-21 | 2014-10-21 | 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 |
| CN201480070232.2A Active CN106029093B (zh) | 2013-10-21 | 2014-10-21 | 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480070232.2A Active CN106029093B (zh) | 2013-10-21 | 2014-10-21 | 脑信号蛋白-4d结合分子治疗神经变性疾病的用途 |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US9598495B2 (enExample) |
| EP (2) | EP3639853A1 (enExample) |
| JP (2) | JP6461944B2 (enExample) |
| KR (4) | KR102602502B1 (enExample) |
| CN (2) | CN116966293A (enExample) |
| AU (3) | AU2014340210B2 (enExample) |
| BR (1) | BR112016009047B1 (enExample) |
| CA (2) | CA3193983A1 (enExample) |
| DK (1) | DK3060252T3 (enExample) |
| EA (1) | EA033072B1 (enExample) |
| ES (1) | ES2773961T3 (enExample) |
| IL (3) | IL275720B (enExample) |
| MX (2) | MX374708B (enExample) |
| NZ (1) | NZ630892A (enExample) |
| PL (1) | PL3060252T3 (enExample) |
| PT (1) | PT3060252T (enExample) |
| SG (2) | SG10201707786QA (enExample) |
| WO (1) | WO2015061330A1 (enExample) |
| ZA (1) | ZA201602686B (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2010245668B2 (en) | 2009-05-08 | 2016-07-14 | Vaccinex, Inc. | Anti-CD100 antibodies and methods for using the same |
| BR112014008885B1 (pt) | 2011-10-11 | 2021-02-17 | Vaccinex, Inc | uso de um anticorpo isolado ou fragmento de ligação ao antígeno do mesmo que se liga especificamente à semaforina-4d para diminuir permeabilidade da barreira hematoencefálica (bbb) em um indivíduo com permeabilidade da bbb aumentada e um transtorno neuroinflamatório |
| US9708601B2 (en) | 2012-04-26 | 2017-07-18 | Vaccinex, Inc. | Fusion proteins to facilitate selection of cells infected with specific immunoglobulin gene recombinant vaccinia virus |
| US10494440B2 (en) | 2012-05-11 | 2019-12-03 | Vaccinex, Inc. | Use of semaphorin-4D binding molecules to promote neurogenesis following stroke |
| WO2014116982A2 (en) * | 2013-01-25 | 2014-07-31 | Brandeis University | Methods of modulating gabaergic inhibitory synapse formation and function |
| EA036591B1 (ru) | 2013-06-25 | 2020-11-26 | Вэксинекс, Инк. | Способ ингибирования, замедления или уменьшения роста раковой опухоли у субъекта |
| NZ630881A (en) | 2013-10-10 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treatment of atherosclerosis |
| NZ630892A (en) | 2013-10-21 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treating neurodegenerative disorders |
| SG11201808554TA (en) | 2016-04-22 | 2018-11-29 | Vaccinex Inc | Integral membrane protein display on poxvirus extracellular enveloped virions |
| RU2747557C2 (ru) | 2016-08-02 | 2021-05-06 | Вэксинекс, Инк. | Улучшенные способы получения библиотек полинуклеотидов в вирусах осповакцины/эукариотических клетках |
| JP7084689B2 (ja) * | 2016-12-08 | 2022-06-15 | 公益財団法人東京都医学総合研究所 | 脳組織の異常を伴う非ヒト動物の作製方法およびその利用 |
| IL267940B2 (en) * | 2017-02-22 | 2025-04-01 | Vaccinex Inc | Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases |
| EP3600419B1 (en) | 2017-03-20 | 2023-08-09 | Vaccinex, Inc. | Treatment of cancer with a semaphorin-4d antibody in combination with an epigenetic modulating agent |
| WO2018204895A1 (en) * | 2017-05-05 | 2018-11-08 | Vaccinex, Inc. | Human anti-semaphorin 4d antibody |
| CN109410218B (zh) * | 2018-10-08 | 2020-08-11 | 百度在线网络技术（北京）有限公司 | 用于生成车辆损伤信息的方法和装置 |
| EP3693380A1 (en) * | 2019-02-11 | 2020-08-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Dual inhibition of plexin-b1 and plexin-b2 |
| JP7610767B2 (ja) * | 2020-06-25 | 2025-01-09 | バクシネックス インコーポレーティッド | レット症候群の処置のためのセマフォリン４ｄ結合分子の使用 |
| WO2022137964A1 (ja) * | 2020-12-23 | 2022-06-30 | 国立大学法人大阪大学 | 軟骨・骨・関節疾患の予防または治療用医薬組成物および軟骨・骨・関節疾患の予防または治療用薬剤のスクリーニング方法 |
| IL311639A (en) * | 2021-09-27 | 2024-05-01 | Vaccinex Inc | Predictive outcome profile for the use of an anti-semaphorin-4D binding compound for the treatment of neurodegenerative diseases |
| WO2023154906A1 (en) | 2022-02-13 | 2023-08-17 | Vaccinex, Inc. | Combination therapy with semaphorin-4d blockade and htt-lowering agent for treatment of huntington's disease |
| WO2024210462A1 (ko) * | 2023-04-03 | 2024-10-10 | 서울대학교산학협력단 | 재조합 세마포린 4d 차단항체를 유효성분으로 포함하는 쇼그렌 증후군 예방 또는 치료용 약학 조성물 |
| CN117924494B (zh) * | 2024-01-23 | 2025-02-25 | 首都医科大学附属北京积水潭医院 | 特异性结合sema4d的抗原结合蛋白及其应用 |
Family Cites Families (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US5892019A (en) | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
| US5070192A (en) | 1988-03-23 | 1991-12-03 | The Johns Hopkins University | Cloned human topoisomerase i: cdna expression, and use for autoantibody detection |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6497872B1 (en) | 1991-07-08 | 2002-12-24 | Neurospheres Holdings Ltd. | Neural transplantation using proliferated multipotent neural stem cells and their progeny |
| FR2686087A1 (fr) | 1992-01-13 | 1993-07-16 | Inst Nat Sante Rech Med | Nouvel antigene lymphocytaire, anticorps correspondant et leurs applications. |
| US5639856A (en) | 1993-09-13 | 1997-06-17 | The Regents Of The University Of California | Semaphorin gene family |
| US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
| US6576754B2 (en) | 1995-11-09 | 2003-06-10 | Dana-Farber Cancer Institute | CD100 antigen and uses therefor |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| ES2273415T3 (es) | 1997-04-07 | 2007-05-01 | Genentech, Inc. | Anticuerpos anti-vegf. |
| US20020032315A1 (en) | 1997-08-06 | 2002-03-14 | Manuel Baca | Anti-vegf antibodies |
| JP2001516226A (ja) | 1997-04-11 | 2001-09-25 | デンドレオン コーポレイション | 腫瘍関連性の抗原に対する免疫応答を誘導するための組成物および方法 |
| EP0892047A3 (de) | 1997-07-09 | 2000-03-08 | Hoechst Marion Roussel Deutschland GmbH | Humanes und murines Semaphorin L |
| US5968829A (en) | 1997-09-05 | 1999-10-19 | Cytotherapeutics, Inc. | Human CNS neural stem cells |
| US6638501B1 (en) | 1997-09-29 | 2003-10-28 | Neurospheres Holdings Ltd. | Use of multipotent neural stem cell progeny to augment non-neural tissues |
| US5958767A (en) | 1998-08-14 | 1999-09-28 | The Children's Medical Center Corp. | Engraftable human neural stem cells |
| ATE407206T1 (de) | 1998-11-10 | 2008-09-15 | Univ Rochester | Methoden zu herstellung von genbanken |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US6849425B1 (en) | 1999-10-14 | 2005-02-01 | Ixsys, Inc. | Methods of optimizing antibody variable region binding affinity |
| JP3787473B2 (ja) | 1999-11-30 | 2006-06-21 | 独立行政法人科学技術振興機構 | セマフォリン受容体 |
| WO2001046384A2 (en) | 1999-12-23 | 2001-06-28 | Cornell Research Foundation, Inc. | A method for isolating and purifying multipotential neural progenitor cells and multipotential neural progenitor cells |
| US6635742B1 (en) | 2000-01-25 | 2003-10-21 | Nuvelo, Inc. | Antibodies specific for semaphorin-like polypeptides |
| WO2002102973A2 (en) | 2001-06-20 | 2002-12-27 | Prochon Biotech Ltd. | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| EP1365018A1 (en) | 2002-05-23 | 2003-11-26 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | CD100 semaphorin in myelination |
| ATE483472T1 (de) | 2002-05-30 | 2010-10-15 | Macrogenics Inc | Cd16a bindungsproteine und verwendung zur behandlung von immunkrankheiten |
| EP1442749A1 (en) * | 2003-01-31 | 2004-08-04 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Use of anti-CD100 antibodies for the treatment and the diagnosis of inflammatory disorder affecting the central nervous system |
| RS20150135A1 (sr) | 2003-05-30 | 2015-08-31 | Genentech Inc. | Tretman sa anti-vegf antitelima |
| CA2548282A1 (en) | 2003-12-11 | 2005-06-30 | Genentech, Inc. | Methods and compositions for inhibiting c-met dimerization and activation |
| US7476724B2 (en) | 2004-08-05 | 2009-01-13 | Genentech, Inc. | Humanized anti-cmet antibodies |
| US20060147449A1 (en) | 2004-11-15 | 2006-07-06 | Brass Lawrence F | Method of using CD100 (or Sema4D) to mediate platelet activation and inflammatory responses |
| JP2008535856A (ja) | 2005-04-07 | 2008-09-04 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス インコーポレイテッド | 癌の診断、検出および治療におけるｓｅｍａ４ｄ |
| JP2007308465A (ja) | 2006-05-15 | 2007-11-29 | Boehringer Ingelheim Internatl Gmbh | 炎症性疾患、自己免疫疾患又は骨吸収異常の治療方法 |
| DE602008004296D1 (de) | 2007-02-14 | 2011-02-17 | Vaccinex Inc | Humanisierte anti-cd100-antikörper |
| WO2009089461A1 (en) | 2008-01-10 | 2009-07-16 | Genentech, Inc. | Plexind1 agonists and their use |
| AU2010245668B2 (en) * | 2009-05-08 | 2016-07-14 | Vaccinex, Inc. | Anti-CD100 antibodies and methods for using the same |
| ES2679043T3 (es) | 2009-05-15 | 2018-08-21 | Irx Therapeutics, Inc. | Inmunoterapia de vacuna |
| NZ605260A (en) | 2010-06-14 | 2013-12-20 | Joseph King Allan | Anti-vegf antibodies and uses thereof |
| DK2711023T3 (en) | 2011-05-13 | 2017-10-16 | Nat Univ Corp Tokyo Medical & Dental Univ | osteogenesis |
| BR112014008885B1 (pt) * | 2011-10-11 | 2021-02-17 | Vaccinex, Inc | uso de um anticorpo isolado ou fragmento de ligação ao antígeno do mesmo que se liga especificamente à semaforina-4d para diminuir permeabilidade da barreira hematoencefálica (bbb) em um indivíduo com permeabilidade da bbb aumentada e um transtorno neuroinflamatório |
| US8790652B2 (en) | 2011-12-06 | 2014-07-29 | Vaccinex, Inc. | Use of the combination of semaphorin-4D inhibitory molecules and VEGF inhibitory molecules to inhibit angiogenesis |
| US9090709B2 (en) | 2012-03-28 | 2015-07-28 | Vaccinex, Inc. | Anti-SEMA4D antibodies and epitopes |
| US9708601B2 (en) | 2012-04-26 | 2017-07-18 | Vaccinex, Inc. | Fusion proteins to facilitate selection of cells infected with specific immunoglobulin gene recombinant vaccinia virus |
| US10494440B2 (en) * | 2012-05-11 | 2019-12-03 | Vaccinex, Inc. | Use of semaphorin-4D binding molecules to promote neurogenesis following stroke |
| EA036591B1 (ru) | 2013-06-25 | 2020-11-26 | Вэксинекс, Инк. | Способ ингибирования, замедления или уменьшения роста раковой опухоли у субъекта |
| NZ630881A (en) | 2013-10-10 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treatment of atherosclerosis |
| NZ630892A (en) | 2013-10-21 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treating neurodegenerative disorders |
| SG11201808554TA (en) | 2016-04-22 | 2018-11-29 | Vaccinex Inc | Integral membrane protein display on poxvirus extracellular enveloped virions |
| RU2747557C2 (ru) | 2016-08-02 | 2021-05-06 | Вэксинекс, Инк. | Улучшенные способы получения библиотек полинуклеотидов в вирусах осповакцины/эукариотических клетках |
| IL267940B2 (en) | 2017-02-22 | 2025-04-01 | Vaccinex Inc | Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases |
-
2014
- 2014-09-11 NZ NZ630892A patent/NZ630892A/en unknown
- 2014-10-21 BR BR112016009047-0A patent/BR112016009047B1/pt active IP Right Grant
- 2014-10-21 PL PL14855074T patent/PL3060252T3/pl unknown
- 2014-10-21 AU AU2014340210A patent/AU2014340210B2/en active Active
- 2014-10-21 IL IL275720A patent/IL275720B/en unknown
- 2014-10-21 JP JP2016524999A patent/JP6461944B2/ja active Active
- 2014-10-21 EP EP19208515.7A patent/EP3639853A1/en active Pending
- 2014-10-21 KR KR1020227025504A patent/KR102602502B1/ko active Active
- 2014-10-21 EA EA201690813A patent/EA033072B1/ru unknown
- 2014-10-21 SG SG10201707786QA patent/SG10201707786QA/en unknown
- 2014-10-21 MX MX2016005050A patent/MX374708B/es active IP Right Grant
- 2014-10-21 CN CN202310282388.8A patent/CN116966293A/zh active Pending
- 2014-10-21 DK DK14855074.2T patent/DK3060252T3/da active
- 2014-10-21 PT PT148550742T patent/PT3060252T/pt unknown
- 2014-10-21 CA CA3193983A patent/CA3193983A1/en active Pending
- 2014-10-21 SG SG11201603167YA patent/SG11201603167YA/en unknown
- 2014-10-21 KR KR1020167013445A patent/KR102308493B1/ko active Active
- 2014-10-21 WO PCT/US2014/061592 patent/WO2015061330A1/en not_active Ceased
- 2014-10-21 US US14/519,965 patent/US9598495B2/en active Active
- 2014-10-21 KR KR1020217030075A patent/KR20210118246A/ko not_active Ceased
- 2014-10-21 IL IL295045A patent/IL295045B2/en unknown
- 2014-10-21 EP EP14855074.2A patent/EP3060252B1/en active Active
- 2014-10-21 CN CN201480070232.2A patent/CN106029093B/zh active Active
- 2014-10-21 CA CA2927841A patent/CA2927841C/en active Active
- 2014-10-21 ES ES14855074T patent/ES2773961T3/es active Active
- 2014-10-21 KR KR1020237038769A patent/KR20230159633A/ko not_active Ceased
-
2015
- 2015-06-29 US US14/753,882 patent/US9249227B2/en active Active
-
2016
- 2016-04-13 IL IL245089A patent/IL245089B/en active IP Right Grant
- 2016-04-19 ZA ZA201602686A patent/ZA201602686B/en unknown
- 2016-04-19 MX MX2020009260A patent/MX2020009260A/es unknown
-
2017
- 2017-03-21 US US15/465,509 patent/US10385136B2/en active Active
-
2018
- 2018-12-26 JP JP2018241924A patent/JP6875363B2/ja active Active
-
2019
- 2019-07-02 US US16/460,593 patent/US10800853B2/en active Active
- 2019-10-28 AU AU2019257379A patent/AU2019257379B2/en active Active
-
2021
- 2021-04-06 AU AU2021202095A patent/AU2021202095B9/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10800853B2 (en) | Use of semaphorin-4D binding molecules for treating neurodegenerative disorders | |
| RU2766341C2 (ru) | Раннее обнаружение активации глиальных клеток при нейродегенеративных или нейровоспалительных заболеваниях | |
| JP6218810B2 (ja) | 卒中後の神経形成を促進するためのセマフォリン−４ｄ結合分子の使用 | |
| CN117597360A (zh) | 脑信号蛋白-4d结合分子在rett综合征治疗中的应用 | |
| EA044133B1 (ru) | Способ лечения симптомов ранней стадии болезни альцгеймера у субъекта |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |