MXPA04005537A - Vacuna y metodo para el tratamiento de enfermedades de las neuronas motoras. - Google Patents
Vacuna y metodo para el tratamiento de enfermedades de las neuronas motoras.Info
- Publication number
- MXPA04005537A MXPA04005537A MXPA04005537A MXPA04005537A MXPA04005537A MX PA04005537 A MXPA04005537 A MX PA04005537A MX PA04005537 A MXPA04005537 A MX PA04005537A MX PA04005537 A MXPA04005537 A MX PA04005537A MX PA04005537 A MXPA04005537 A MX PA04005537A
- Authority
- MX
- Mexico
- Prior art keywords
- ala ala
- cop
- vaccine
- mice
- als
- Prior art date
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 47
- 208000026072 Motor neurone disease Diseases 0.000 title claims abstract description 22
- 238000011282 treatment Methods 0.000 title claims description 25
- 238000000034 method Methods 0.000 title description 22
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 89
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 74
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 44
- 229930195712 glutamate Natural products 0.000 claims abstract description 43
- 229920001184 polypeptide Polymers 0.000 claims abstract description 35
- 239000002671 adjuvant Substances 0.000 claims abstract description 30
- 231100000419 toxicity Toxicity 0.000 claims abstract description 24
- 230000001988 toxicity Effects 0.000 claims abstract description 24
- 239000013543 active substance Substances 0.000 claims abstract description 20
- 230000004224 protection Effects 0.000 claims abstract description 20
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 18
- 206010056677 Nerve degeneration Diseases 0.000 claims abstract description 9
- 208000005264 motor neuron disease Diseases 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 27
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 15
- 229960004181 riluzole Drugs 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 230000000750 progressive effect Effects 0.000 claims description 12
- 229940047712 aluminum hydroxyphosphate Drugs 0.000 claims description 7
- 208000034189 Sclerosis Diseases 0.000 claims description 6
- 206010028289 Muscle atrophy Diseases 0.000 claims description 4
- 101100273635 Rattus norvegicus Ccn5 gene Proteins 0.000 claims description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 4
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 4
- 201000000585 muscular atrophy Diseases 0.000 claims description 4
- 201000002241 progressive bulbar palsy Diseases 0.000 claims description 4
- 206010006542 Bulbar palsy Diseases 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 3
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 3
- 230000020763 muscle atrophy Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 206010061818 Disease progression Diseases 0.000 abstract description 4
- 230000005750 disease progression Effects 0.000 abstract description 4
- 241000699670 Mus sp. Species 0.000 description 110
- 210000002161 motor neuron Anatomy 0.000 description 45
- 229920001577 copolymer Polymers 0.000 description 35
- 210000003994 retinal ganglion cell Anatomy 0.000 description 32
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 27
- 235000001014 amino acid Nutrition 0.000 description 27
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 25
- 230000000694 effects Effects 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 230000003053 immunization Effects 0.000 description 23
- 239000004472 Lysine Substances 0.000 description 22
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 21
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 21
- 235000004279 alanine Nutrition 0.000 description 21
- 238000002649 immunization Methods 0.000 description 21
- 235000018977 lysine Nutrition 0.000 description 21
- 235000013922 glutamic acid Nutrition 0.000 description 20
- 239000004220 glutamic acid Substances 0.000 description 20
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 238000011830 transgenic mouse model Methods 0.000 description 20
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 20
- 235000002374 tyrosine Nutrition 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 238000002255 vaccination Methods 0.000 description 19
- 241000699660 Mus musculus Species 0.000 description 18
- 229920001897 terpolymer Polymers 0.000 description 18
- 210000003169 central nervous system Anatomy 0.000 description 17
- 230000004083 survival effect Effects 0.000 description 17
- 230000033001 locomotion Effects 0.000 description 16
- 230000007850 degeneration Effects 0.000 description 15
- 210000003205 muscle Anatomy 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 210000003135 vibrissae Anatomy 0.000 description 14
- 210000000256 facial nerve Anatomy 0.000 description 13
- 210000001744 T-lymphocyte Anatomy 0.000 description 12
- VCXWRWYFJLXITF-AUTRQRHGSA-N Tyr-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VCXWRWYFJLXITF-AUTRQRHGSA-N 0.000 description 12
- 230000006378 damage Effects 0.000 description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 10
- 230000004770 neurodegeneration Effects 0.000 description 10
- 241000282412 Homo Species 0.000 description 9
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000001815 facial effect Effects 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 201000008752 progressive muscular atrophy Diseases 0.000 description 7
- 208000002320 spinal muscular atrophy Diseases 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 239000004475 Arginine Substances 0.000 description 6
- 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 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 210000005036 nerve Anatomy 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 210000001525 retina Anatomy 0.000 description 6
- 108010072051 Glatiramer Acetate Proteins 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 206010033799 Paralysis Diseases 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- 230000001363 autoimmune Effects 0.000 description 5
- 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 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 201000010901 lateral sclerosis Diseases 0.000 description 5
- 230000037023 motor activity Effects 0.000 description 5
- 210000004940 nucleus Anatomy 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- -1 superoxide anions Chemical class 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 4
- 102100032047 Alsin Human genes 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000010428 Muscle Weakness Diseases 0.000 description 4
- 206010028372 Muscular weakness Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 4
- 108010012715 Superoxide dismutase Proteins 0.000 description 4
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000013532 laser treatment Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 229920005604 random copolymer Polymers 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 4
- FJVAQLJNTSUQPY-CIUDSAMLSA-N Ala-Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN FJVAQLJNTSUQPY-CIUDSAMLSA-N 0.000 description 3
- 150000008574 D-amino acids Chemical class 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 102000006354 HLA-DR Antigens Human genes 0.000 description 3
- 108010058597 HLA-DR Antigens Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000000763 evoking effect Effects 0.000 description 3
- 230000003492 excitotoxic effect Effects 0.000 description 3
- 231100000063 excitotoxicity Toxicity 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 208000013094 juvenile primary lateral sclerosis Diseases 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000007512 neuronal protection Effects 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 210000001328 optic nerve Anatomy 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- YLOCGHYTXIINAI-XKUOMLDTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLOCGHYTXIINAI-XKUOMLDTSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 2
- HMRWQTHUDVXMGH-GUBZILKMSA-N Ala-Glu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HMRWQTHUDVXMGH-GUBZILKMSA-N 0.000 description 2
- 101710187109 Alsin Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102100031562 Excitatory amino acid transporter 2 Human genes 0.000 description 2
- JJKKWYQVHRUSDG-GUBZILKMSA-N Glu-Ala-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O JJKKWYQVHRUSDG-GUBZILKMSA-N 0.000 description 2
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 2
- HRBYTAIBKPNZKQ-AVGNSLFASA-N Glu-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O HRBYTAIBKPNZKQ-AVGNSLFASA-N 0.000 description 2
- AQNYKMCFCCZEEL-JYJNAYRXSA-N Glu-Lys-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AQNYKMCFCCZEEL-JYJNAYRXSA-N 0.000 description 2
- 101000776160 Homo sapiens Alsin Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000011823 Juvenile amyotrophic lateral sclerosis Diseases 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 229930195714 L-glutamate Natural products 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
- GJJQCBVRWDGLMQ-GUBZILKMSA-N Lys-Glu-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O GJJQCBVRWDGLMQ-GUBZILKMSA-N 0.000 description 2
- ODUQLUADRKMHOZ-JYJNAYRXSA-N Lys-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)O ODUQLUADRKMHOZ-JYJNAYRXSA-N 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- IELISNUVHBKYBX-XDTLVQLUSA-N Tyr-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IELISNUVHBKYBX-XDTLVQLUSA-N 0.000 description 2
- NQJDICVXXIMMMB-XDTLVQLUSA-N Tyr-Glu-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O NQJDICVXXIMMMB-XDTLVQLUSA-N 0.000 description 2
- JAGGEZACYAAMIL-CQDKDKBSSA-N Tyr-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JAGGEZACYAAMIL-CQDKDKBSSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 2
- 108010028939 alanyl-alanyl-lysyl-alanine Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 201000008266 amyotrophic lateral sclerosis type 2 Diseases 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 208000019995 familial amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229940042385 glatiramer Drugs 0.000 description 2
- 229960003776 glatiramer acetate Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 208000032799 juvenile amyotrophic lateral sclerosis type 2 Diseases 0.000 description 2
- 230000002197 limbic effect Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004112 neuroprotection Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000001575 pathological effect 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
- 235000008729 phenylalanine Nutrition 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000001374 small-angle light scattering Methods 0.000 description 2
- 101150062190 sod1 gene Proteins 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 238000010972 statistical evaluation Methods 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 230000001360 synchronised effect Effects 0.000 description 2
- 238000013417 toxicology model Methods 0.000 description 2
- 210000004127 vitreous body Anatomy 0.000 description 2
- KNCHTBNNSQSLRV-YFKPBYRVSA-N (2s)-6-amino-2-[(2,2,2-trifluoroacetyl)amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)C(F)(F)F KNCHTBNNSQSLRV-YFKPBYRVSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- 101150001232 ALS gene Proteins 0.000 description 1
- 101150036028 ALS2 gene Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 1
- ROLXPVQSRCPVGK-XDTLVQLUSA-N Ala-Glu-Tyr Chemical compound N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O ROLXPVQSRCPVGK-XDTLVQLUSA-N 0.000 description 1
- QUIGLPSHIFPEOV-CIUDSAMLSA-N Ala-Lys-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O QUIGLPSHIFPEOV-CIUDSAMLSA-N 0.000 description 1
- VCSABYLVNWQYQE-SRVKXCTJSA-N Ala-Lys-Lys Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O VCSABYLVNWQYQE-SRVKXCTJSA-N 0.000 description 1
- VCSABYLVNWQYQE-UHFFFAOYSA-N Ala-Lys-Lys Natural products NCCCCC(NC(=O)C(N)C)C(=O)NC(CCCCN)C(O)=O VCSABYLVNWQYQE-UHFFFAOYSA-N 0.000 description 1
- KQESEZXHYOUIIM-CQDKDKBSSA-N Ala-Lys-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KQESEZXHYOUIIM-CQDKDKBSSA-N 0.000 description 1
- AENHOIXXHKNIQL-AUTRQRHGSA-N Ala-Tyr-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]([NH3+])C)CC1=CC=C(O)C=C1 AENHOIXXHKNIQL-AUTRQRHGSA-N 0.000 description 1
- XAXMJQUMRJAFCH-CQDKDKBSSA-N Ala-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 XAXMJQUMRJAFCH-CQDKDKBSSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 229920001453 Arcel Polymers 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 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
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 1
- 102000034575 Glutamate transporters Human genes 0.000 description 1
- 108091006151 Glutamate transporters Proteins 0.000 description 1
- 108010067218 Guanine Nucleotide Exchange Factors Proteins 0.000 description 1
- 102000016285 Guanine Nucleotide Exchange Factors Human genes 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 101000866287 Homo sapiens Excitatory amino acid transporter 2 Proteins 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 101000664887 Homo sapiens Superoxide dismutase [Cu-Zn] Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000001393 Lathyrism Diseases 0.000 description 1
- BXPHMHQHYHILBB-BZSNNMDCSA-N Lys-Lys-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BXPHMHQHYHILBB-BZSNNMDCSA-N 0.000 description 1
- MYTOTTSMVMWVJN-STQMWFEESA-N Lys-Tyr Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 MYTOTTSMVMWVJN-STQMWFEESA-N 0.000 description 1
- XYLSGAWRCZECIQ-JYJNAYRXSA-N Lys-Tyr-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 XYLSGAWRCZECIQ-JYJNAYRXSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000019430 Motor disease Diseases 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010028293 Muscle contractions involuntary Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 208000030768 Optic nerve injury Diseases 0.000 description 1
- 241000566145 Otus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
- 229960005054 acepromazine Drugs 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 210000002226 anterior horn cell Anatomy 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- FLASNYPZGWUPSU-SICDJOISSA-N chitosan Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)N)O[C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)N)O[C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)N)O[C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)N)O[C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)N)O[C@H]1[C@H](O)[C@H]([C@@H](O[C@@H]1CO)O[C@@H]1[C@H](O[C@@H](O[C@@H]2[C@H](O[C@@H](O)[C@H](N)[C@H]2O)CO)[C@H](N)[C@H]1O)CO)NC(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1N FLASNYPZGWUPSU-SICDJOISSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 229940038717 copaxone Drugs 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000013628 high molecular weight specie Substances 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 102000056070 human SOD1 Human genes 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007658 neurological function Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 238000011859 neuroprotective therapy Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940069575 rompun Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 230000025185 skeletal muscle atrophy Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000005809 status epilepticus Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- WGTODYJZXSJIAG-UHFFFAOYSA-N tetramethylrhodamine chloride Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C(O)=O WGTODYJZXSJIAG-UHFFFAOYSA-N 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0007—Nervous system antigens; Prions
-
- 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
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33613901P | 2001-12-06 | 2001-12-06 | |
| PCT/IL2002/000979 WO2003047500A2 (en) | 2001-12-06 | 2002-12-05 | Vaccine and method for treatment of motor neurone diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04005537A true MXPA04005537A (es) | 2004-11-01 |
Family
ID=23314742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04005537A MXPA04005537A (es) | 2001-12-06 | 2002-12-05 | Vacuna y metodo para el tratamiento de enfermedades de las neuronas motoras. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7351686B2 (enExample) |
| EP (1) | EP1429800B1 (enExample) |
| JP (1) | JP4542339B2 (enExample) |
| KR (1) | KR20040081431A (enExample) |
| CN (2) | CN1617736A (enExample) |
| AT (1) | ATE422362T1 (enExample) |
| AU (1) | AU2002353486B2 (enExample) |
| CA (1) | CA2469092C (enExample) |
| CY (1) | CY1109044T1 (enExample) |
| DE (1) | DE60231131D1 (enExample) |
| DK (1) | DK1429800T3 (enExample) |
| ES (1) | ES2322566T3 (enExample) |
| HU (1) | HU228207B1 (enExample) |
| IL (1) | IL160105A0 (enExample) |
| IS (1) | IS2670B (enExample) |
| MX (1) | MXPA04005537A (enExample) |
| NO (1) | NO336231B1 (enExample) |
| NZ (1) | NZ533356A (enExample) |
| PL (1) | PL205469B1 (enExample) |
| PT (1) | PT1429800E (enExample) |
| RU (1) | RU2303996C2 (enExample) |
| SI (1) | SI1429800T1 (enExample) |
| WO (1) | WO2003047500A2 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7399740B2 (en) | 2001-06-28 | 2008-07-15 | Yeda Research And Development Co. Ltd. | Poly-Glu,Tyr for neuroprotective therapy |
| WO2004060265A2 (en) * | 2003-01-07 | 2004-07-22 | Yeda Research And Development Co. Ltd. | Eye-drop vaccine containing copolymer 1 for therapeutic immunization |
| CA2546077C (en) | 2003-11-12 | 2016-07-05 | Yeda Research And Development Co. Ltd. | Vaccine and method for treatment of neurodegenerative diseases |
| DK1701730T3 (da) | 2003-12-09 | 2013-11-25 | Yeda Res & Dev | Fremgangsmåde og vaccine omfattende copolymer 1 til behandling af psykiatriske forstyrrelser |
| EP1778286A4 (en) * | 2004-03-03 | 2009-04-08 | Teva Pharma | COMBINATION THERAPY WITH ACETATE OF GLATIRAMER AND RILUZOLE |
| US7655221B2 (en) | 2004-05-07 | 2010-02-02 | Peptimmune, Inc. | Methods of treating disease with random copolymers |
| CA2565819A1 (en) * | 2004-05-07 | 2005-12-01 | Peptimmune, Inc. | Methods of treating disease with random copolymers |
| JP5241012B2 (ja) * | 2005-07-15 | 2013-07-17 | ノバルティス アーゲー | Pamps、病原体関連分子パターン |
| CN100448481C (zh) * | 2006-06-22 | 2009-01-07 | 中国科学院遗传与发育生物学研究所 | xCT蛋白及其编码基因的新用途 |
| WO2009040814A1 (en) | 2007-09-24 | 2009-04-02 | Hadasit Medical Research Services & Development Ltd | Use of copolymer 1 for treatment of muscular dystrophy |
| USRE49251E1 (en) | 2010-01-04 | 2022-10-18 | Mapi Pharma Ltd. | Depot systems comprising glatiramer or pharmacologically acceptable salt thereof |
| US8759302B2 (en) * | 2010-03-16 | 2014-06-24 | Teva Pharmaceutical Industries, Ltd. | Methods of treating a subject afflicted with an autoimmune disease using predictive biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis |
| EA025780B1 (ru) | 2010-10-11 | 2017-01-30 | Тева Фармасьютикал Индастриз Лтд. | Цитокиновые биомаркеры в качестве биомаркеров, прогнозирующих клинический ответ на глатирамер ацетат |
| ES2601892T3 (es) | 2011-04-21 | 2017-02-16 | Mapi Pharma Limited | Pentapolímero aleatorio para el tratamiento de enfermedades autoinmunes |
| MX2014004309A (es) | 2011-10-10 | 2015-07-06 | Teva Pharma | Polimorfismos de nucleotidos individuales utiles para predecir una respuesta clinica para el acetato de glatiramer. |
| US9861686B2 (en) * | 2011-12-05 | 2018-01-09 | Ben-Gurion University Of The Negev Research & Development Authority | Diagnostic and therapeutic methods and their application in amyotrophic lateral sclerosis (ALS) |
| KR20140145173A (ko) * | 2012-03-26 | 2014-12-22 | 예다 리서치 앤드 디벨럽먼트 캄파니 리미티드 | 알츠하이머 질병 진단 및 알츠하이머 질병 진행 진단용 세포 마커 |
| EP2892353A4 (en) | 2012-09-10 | 2016-10-26 | Yeda Res & Dev | INDIVIDUALIZED IMMUNOMODULATION THERAPY FOR NEURODEGENERATIVE ILLNESSES, CNS LESIONS AND AGGREGATIVE DEMENTIA |
| US12097292B2 (en) | 2016-08-28 | 2024-09-24 | Mapi Pharma Ltd. | Process for preparing microparticles containing glatiramer acetate |
| AU2017319728B2 (en) | 2016-08-31 | 2024-09-05 | Mapi Pharma Ltd | Depot systems comprising glatiramer acetate |
| IL316573A (en) | 2017-03-26 | 2024-12-01 | Mapi Pharma Ltd | Storage systems containing glatiramer acetate for the treatment of multiple sclerosis |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL36670A (en) * | 1971-04-21 | 1974-09-10 | Sela M | Therapeutic basic copolymers of amino acids |
| US3849650A (en) | 1973-03-29 | 1974-11-19 | Picker Corp | Automatic x-ray inspection system |
| IL113812A (en) | 1994-05-24 | 2000-06-29 | Yeda Res & Dev | Copolymer-1 pharmaceutical compositions containing it and its use |
| SE505316C2 (sv) * | 1995-10-17 | 1997-08-04 | Kenneth G Haglid | Användning av proteinet S-100b för framställning av läkemedel för nervceller |
| RU2211697C2 (ru) * | 1996-09-27 | 2003-09-10 | Гилфорд Фармасьютикалз Инк. | Способ лечения глутаматных расстройств |
| JP2002503658A (ja) * | 1998-02-13 | 2002-02-05 | オートイミューン インク | COP−1及びTh−2促進性サイトカインを使用した、多発性硬化症の治療 |
| US20030108528A1 (en) | 1998-05-19 | 2003-06-12 | Michal Eisenbach-Schwartz | Activated t-cells, nervous system-specific antigens and their uses |
| US20020072493A1 (en) | 1998-05-19 | 2002-06-13 | Yeda Research And Development Co. Ltd. | Activated T cells, nervous system-specific antigens and their uses |
| WO1999060021A2 (en) | 1998-05-19 | 1999-11-25 | Yeda Research And Development Co. Ltd. | Use of activated t cells, nervous system-specific antigens for treating disorders of the nevrous system |
| EP1039929A1 (en) | 1998-07-21 | 2000-10-04 | YEDA RESEARCH AND DEVELOPMENT Co. Ltd. | Activated t-cells and their uses |
| JP2003521448A (ja) | 1998-07-23 | 2003-07-15 | ザ・プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ | 合成ペプチドおよび自己免疫疾患治療のための使用方法 |
| RU2155063C1 (ru) * | 1999-10-20 | 2000-08-27 | Санкт-Петербургская общественная организация "Институт биорегуляции и геронтологии" | Тетрапептид, стимулирующий функциональную активность нейронов, фармакологическое средство на его основе и способ его применения |
| HK1054507B (zh) * | 2000-01-20 | 2008-10-31 | 耶达研究及发展有限公司 | 共聚物1和相关肽和多肽及其处理过的t细胞在神经保护性治疗中的用途 |
| DE60116467T2 (de) | 2000-06-07 | 2006-11-02 | Yeda Research And Development Co., Ltd. | Verwendung des Copolymer-1 Peptids sowie von damit verwandten Peptiden und Polypeptiden und von damit behandelten T-Zellen zur Neuroprotektion gegen die Toxizität von Glutamat |
| WO2002076503A1 (en) * | 2000-06-20 | 2002-10-03 | Mayo Foundation For Medical Education And Research | Treatment of central nervous system diseases by antibodies against glatiramer acetate |
| US6835711B2 (en) * | 2001-06-28 | 2004-12-28 | Yeda Research And Development Co. Ltd. | Use of poly-Glu,Tyr for neuroprotective therapy |
| US7399740B2 (en) * | 2001-06-28 | 2008-07-15 | Yeda Research And Development Co. Ltd. | Poly-Glu,Tyr for neuroprotective therapy |
-
2002
- 2002-12-05 US US10/485,576 patent/US7351686B2/en not_active Expired - Lifetime
- 2002-12-05 EP EP02788511A patent/EP1429800B1/en not_active Expired - Lifetime
- 2002-12-05 HU HU0500039A patent/HU228207B1/hu not_active IP Right Cessation
- 2002-12-05 DE DE60231131T patent/DE60231131D1/de not_active Expired - Lifetime
- 2002-12-05 KR KR10-2004-7008780A patent/KR20040081431A/ko not_active Ceased
- 2002-12-05 DK DK02788511T patent/DK1429800T3/da active
- 2002-12-05 AU AU2002353486A patent/AU2002353486B2/en not_active Ceased
- 2002-12-05 PL PL370070A patent/PL205469B1/pl unknown
- 2002-12-05 WO PCT/IL2002/000979 patent/WO2003047500A2/en not_active Ceased
- 2002-12-05 JP JP2003548761A patent/JP4542339B2/ja not_active Expired - Fee Related
- 2002-12-05 SI SI200230800T patent/SI1429800T1/sl unknown
- 2002-12-05 CN CNA028277015A patent/CN1617736A/zh active Pending
- 2002-12-05 RU RU2004120536/14A patent/RU2303996C2/ru not_active IP Right Cessation
- 2002-12-05 CN CN201110056639.8A patent/CN102151330B/zh not_active Expired - Fee Related
- 2002-12-05 AT AT02788511T patent/ATE422362T1/de active
- 2002-12-05 NZ NZ533356A patent/NZ533356A/en not_active IP Right Cessation
- 2002-12-05 MX MXPA04005537A patent/MXPA04005537A/es active IP Right Grant
- 2002-12-05 IL IL16010502A patent/IL160105A0/xx unknown
- 2002-12-05 CA CA2469092A patent/CA2469092C/en not_active Expired - Fee Related
- 2002-12-05 PT PT02788511T patent/PT1429800E/pt unknown
- 2002-12-05 ES ES02788511T patent/ES2322566T3/es not_active Expired - Lifetime
-
2004
- 2004-06-03 IS IS7296A patent/IS2670B/is unknown
- 2004-07-05 NO NO20042833A patent/NO336231B1/no not_active IP Right Cessation
-
2009
- 2009-05-06 CY CY20091100485T patent/CY1109044T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7351686B2 (en) | Method for neuronal protection in amyotrophic lateral sclerosis by a vaccine comprising Copolymer-1 or Copolymer-1 related peptides | |
| US9517256B2 (en) | Vaccine and method for treatment of neurodegenerative diseases | |
| JP2005515198A6 (ja) | 運動ニューロン疾患を治療するためのワクチン及び方法 | |
| ES2315371T3 (es) | Uso de poli-glu,tyr para terapia neuroprotectora del snc o snp. | |
| JP5291878B2 (ja) | 治療的免疫のためのコポリマー1を含む点眼ワクチン | |
| JP2005515198A5 (enExample) | ||
| US7399740B2 (en) | Poly-Glu,Tyr for neuroprotective therapy | |
| HK1067043B (en) | Vaccine and use thereof for treatment of amyotrophic lateral sclerosis | |
| IL160105A (en) | Vaccine for treatment of amyotrophic lateral sclerosis (als) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |