ES2740127T3 - Tratamiento de subpoblaciones con enfermedad de Alzheimer con inmunoglobulina G combinada - Google Patents
Tratamiento de subpoblaciones con enfermedad de Alzheimer con inmunoglobulina G combinada Download PDFInfo
- Publication number
- ES2740127T3 ES2740127T3 ES14730660T ES14730660T ES2740127T3 ES 2740127 T3 ES2740127 T3 ES 2740127T3 ES 14730660 T ES14730660 T ES 14730660T ES 14730660 T ES14730660 T ES 14730660T ES 2740127 T3 ES2740127 T3 ES 2740127T3
- Authority
- ES
- Spain
- Prior art keywords
- subject
- weeks
- igg
- alzheimer
- administration
- 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.)
- Active
Links
- 229940027941 immunoglobulin g Drugs 0.000 title claims abstract description 277
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 171
- 238000011282 treatment Methods 0.000 title claims abstract description 157
- 239000000203 mixture Substances 0.000 claims abstract description 82
- 230000037396 body weight Effects 0.000 claims abstract description 54
- 108700028369 Alleles Proteins 0.000 claims abstract description 49
- 229940098197 human immunoglobulin g Drugs 0.000 claims abstract description 35
- 238000011285 therapeutic regimen Methods 0.000 claims abstract description 26
- 238000001990 intravenous administration Methods 0.000 claims description 17
- 238000007920 subcutaneous administration Methods 0.000 claims description 6
- 230000003442 weekly effect Effects 0.000 claims description 6
- 238000007918 intramuscular administration Methods 0.000 claims description 5
- 230000003340 mental effect Effects 0.000 claims description 5
- 238000000185 intracerebroventricular administration Methods 0.000 claims description 4
- 238000007913 intrathecal administration Methods 0.000 claims description 4
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 230000006996 mental state Effects 0.000 abstract description 52
- 238000000034 method Methods 0.000 description 94
- 239000000902 placebo Substances 0.000 description 91
- 229940068196 placebo Drugs 0.000 description 91
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 58
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 56
- 230000008859 change Effects 0.000 description 50
- 206010012289 Dementia Diseases 0.000 description 41
- 239000003814 drug Substances 0.000 description 32
- 108090000765 processed proteins & peptides Proteins 0.000 description 32
- 238000011156 evaluation Methods 0.000 description 31
- 210000003169 central nervous system Anatomy 0.000 description 29
- 210000002381 plasma Anatomy 0.000 description 29
- 238000002560 therapeutic procedure Methods 0.000 description 29
- 210000004556 brain Anatomy 0.000 description 27
- 230000000694 effects Effects 0.000 description 27
- 108060003951 Immunoglobulin Proteins 0.000 description 26
- 102000018358 immunoglobulin Human genes 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
- 208000037259 Amyloid Plaque Diseases 0.000 description 24
- 201000010099 disease Diseases 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 23
- 230000001149 cognitive effect Effects 0.000 description 23
- YNDIAUKFXKEXSV-CRYLGTRXSA-N florbetapir F-18 Chemical compound C1=CC(NC)=CC=C1\C=C\C1=CC=C(OCCOCCOCC[18F])N=C1 YNDIAUKFXKEXSV-CRYLGTRXSA-N 0.000 description 20
- 229940079593 drug Drugs 0.000 description 19
- 210000004086 maxillary sinus Anatomy 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- 239000000843 powder Substances 0.000 description 18
- 108010003272 Hyaluronate lyase Proteins 0.000 description 16
- 102000001974 Hyaluronidases Human genes 0.000 description 16
- 229960002773 hyaluronidase Drugs 0.000 description 16
- 102000013498 tau Proteins Human genes 0.000 description 16
- 108010026424 tau Proteins Proteins 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 230000008901 benefit Effects 0.000 description 15
- 239000000969 carrier Substances 0.000 description 14
- 238000002595 magnetic resonance imaging Methods 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- 101150037123 APOE gene Proteins 0.000 description 12
- 210000003928 nasal cavity Anatomy 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000000090 biomarker Substances 0.000 description 11
- 238000003384 imaging method Methods 0.000 description 11
- 229940072221 immunoglobulins Drugs 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 210000003901 trigeminal nerve Anatomy 0.000 description 11
- 230000007423 decrease Effects 0.000 description 10
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 10
- 238000001802 infusion Methods 0.000 description 10
- 230000036470 plasma concentration Effects 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 230000002861 ventricular Effects 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 9
- 238000002600 positron emission tomography Methods 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 230000002490 cerebral effect Effects 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 229950001863 bapineuzumab Drugs 0.000 description 7
- 210000002850 nasal mucosa Anatomy 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000007921 spray Substances 0.000 description 7
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 230000008499 blood brain barrier function Effects 0.000 description 5
- 210000001218 blood-brain barrier Anatomy 0.000 description 5
- 230000002354 daily effect Effects 0.000 description 5
- 230000004153 glucose metabolism Effects 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000002483 medication Methods 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 210000000118 neural pathway Anatomy 0.000 description 5
- 230000010004 neural pathway Effects 0.000 description 5
- 230000000926 neurological effect Effects 0.000 description 5
- 210000001706 olfactory mucosa Anatomy 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 108010025628 Apolipoproteins E Proteins 0.000 description 4
- 102000013918 Apolipoproteins E Human genes 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000006866 deterioration Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 4
- 229960004640 memantine Drugs 0.000 description 4
- 238000001050 pharmacotherapy Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 229960001685 tacrine Drugs 0.000 description 4
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- AOYNUTHNTBLRMT-MXWOLSILSA-N 2-Deoxy-2(F-18)fluoro-2-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H]([18F])C=O AOYNUTHNTBLRMT-MXWOLSILSA-N 0.000 description 3
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 3
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 3
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 3
- 206010003694 Atrophy Diseases 0.000 description 3
- 206010008096 Cerebral atrophy Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 208000029462 Immunodeficiency disease Diseases 0.000 description 3
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000000133 brain stem Anatomy 0.000 description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229960003530 donepezil Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 206010020718 hyperplasia Diseases 0.000 description 3
- 230000007813 immunodeficiency Effects 0.000 description 3
- 210000000274 microglia Anatomy 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 210000000196 olfactory nerve Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001671 psychotherapy Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229950007874 solanezumab Drugs 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000000982 vasogenic effect Effects 0.000 description 3
- 230000001755 vocal effect Effects 0.000 description 3
- 238000010176 18-FDG-positron emission tomography Methods 0.000 description 2
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 102100034112 Alkyldihydroxyacetonephosphate synthase, peroxisomal Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 102100029470 Apolipoprotein E Human genes 0.000 description 2
- 101710095339 Apolipoprotein E Proteins 0.000 description 2
- 108010060219 Apolipoprotein E2 Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010063045 Effusion Diseases 0.000 description 2
- 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 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 101000799143 Homo sapiens Alkyldihydroxyacetonephosphate synthase, peroxisomal Proteins 0.000 description 2
- 206010021034 Hypometabolism Diseases 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 102000012547 Olfactory receptors Human genes 0.000 description 2
- 108050002069 Olfactory receptors Proteins 0.000 description 2
- 238000012879 PET imaging Methods 0.000 description 2
- 208000031951 Primary immunodeficiency Diseases 0.000 description 2
- 206010067275 Vasogenic cerebral oedema Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003941 amyloidogenesis Effects 0.000 description 2
- 238000000848 angular dependent Auger electron spectroscopy Methods 0.000 description 2
- 229940039856 aricept Drugs 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 210000005080 cortical synaptosome Anatomy 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000002451 diencephalon Anatomy 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 229940108366 exelon Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 229960003980 galantamine Drugs 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 210000005230 lumbar spinal cord Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000001259 mesencephalon Anatomy 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 238000002625 monoclonal antibody therapy Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000000492 nasalseptum Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 210000000956 olfactory bulb Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000002360 prefrontal effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 210000004129 prosencephalon Anatomy 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229940051845 razadyne Drugs 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 210000001202 rhombencephalon Anatomy 0.000 description 2
- 229960004136 rivastigmine Drugs 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000022099 Alzheimer disease 2 Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 108010060215 Apolipoprotein E3 Proteins 0.000 description 1
- 102000008128 Apolipoprotein E3 Human genes 0.000 description 1
- 230000007082 Aβ accumulation Effects 0.000 description 1
- 108010027740 BHT 3009 Proteins 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 201000010717 Bruton-type agammaglobulinemia Diseases 0.000 description 1
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 108091005944 Cerulean Proteins 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 108010017480 Hemosiderin Proteins 0.000 description 1
- 101000887490 Homo sapiens Guanine nucleotide-binding protein G(z) subunit alpha Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 102100021102 Hyaluronidase PH-20 Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 208000007924 IgA Deficiency Diseases 0.000 description 1
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010016230 MBP-8298 Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 102000012412 Presenilin-1 Human genes 0.000 description 1
- 108010036908 Presenilin-2 Proteins 0.000 description 1
- 102000012419 Presenilin-2 Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 101150096148 Psen2 gene Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- BKRGVLQUQGGVSM-KBXCAEBGSA-N Revanil Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 BKRGVLQUQGGVSM-KBXCAEBGSA-N 0.000 description 1
- 101150055528 SPAM1 gene Proteins 0.000 description 1
- 206010054979 Secondary immunodeficiency Diseases 0.000 description 1
- 206010039915 Selective IgA immunodeficiency Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 208000002667 Subdural Hematoma Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010047295 Ventricular hypertrophy Diseases 0.000 description 1
- 208000016349 X-linked agammaglobulinemia Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001896 anti-amyloidogenic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000004208 basal nucleus of meynert Anatomy 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 210000001052 bipolar neuron Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960004596 cabergoline Drugs 0.000 description 1
- 229940112129 campath Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005800 cardiovascular problem Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 210000004289 cerebral ventricle Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001448 chloropyramine Drugs 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000006998 cognitive state Effects 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- RCTCWZRPYFBGLQ-WMCRPSJMSA-N dirucotide Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 RCTCWZRPYFBGLQ-WMCRPSJMSA-N 0.000 description 1
- 229950003050 dirucotide Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 101150097231 eg gene Proteins 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000003619 fibrillary effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 102000052301 human GNAZ Human genes 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 201000007156 immunoglobulin alpha deficiency Diseases 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000008449 language Effects 0.000 description 1
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 description 1
- 229960004577 laquinimod Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229960003587 lisuride Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 210000002698 mandibular nerve Anatomy 0.000 description 1
- 210000001352 masseter muscle Anatomy 0.000 description 1
- 210000004228 maxillary nerve Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 229960001165 modafinil Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000001703 neuroimmune Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 238000010855 neuropsychological testing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 210000004273 ophthalmic nerve Anatomy 0.000 description 1
- 208000025661 ovarian cyst Diseases 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960004851 pergolide Drugs 0.000 description 1
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000003446 pia mater Anatomy 0.000 description 1
- 238000001470 plasma protein fractionation Methods 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229950003486 ponezumab Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229940098458 powder spray Drugs 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000009290 primary effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- -1 pyribedil Chemical compound 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 208000029138 selective IgA deficiency disease Diseases 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 229960003946 selegiline Drugs 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002330 subarachnoid space Anatomy 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 210000001738 temporomandibular joint Anatomy 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000001944 turbinate Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000007497 verbal memory Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003936 working memory Effects 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
- A61K39/39516—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum from serum, plasma
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Mycology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361855062P | 2013-05-06 | 2013-05-06 | |
| US201361833447P | 2013-06-10 | 2013-06-10 | |
| US201361844732P | 2013-07-10 | 2013-07-10 | |
| US201361886464P | 2013-10-03 | 2013-10-03 | |
| PCT/US2014/036848 WO2014182631A1 (en) | 2013-05-06 | 2014-05-05 | Treatment of alzheimer's disease subpopulations with pooled immunoglobulin g |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2740127T3 true ES2740127T3 (es) | 2020-02-05 |
Family
ID=50943566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14730660T Active ES2740127T3 (es) | 2013-05-06 | 2014-05-05 | Tratamiento de subpoblaciones con enfermedad de Alzheimer con inmunoglobulina G combinada |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20140328856A1 (enExample) |
| EP (2) | EP2994160B1 (enExample) |
| JP (1) | JP6424210B2 (enExample) |
| AU (4) | AU2014262890B2 (enExample) |
| DK (1) | DK2994160T3 (enExample) |
| ES (1) | ES2740127T3 (enExample) |
| HR (1) | HRP20191383T1 (enExample) |
| HU (1) | HUE044737T2 (enExample) |
| LT (1) | LT2994160T (enExample) |
| PL (1) | PL2994160T3 (enExample) |
| PT (1) | PT2994160T (enExample) |
| WO (1) | WO2014182631A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4289820A3 (en) | 2014-03-21 | 2024-03-13 | Alzheon, Inc. | Compounds for use in treating alzheimer's disease in apoe4+/+ patients |
| WO2016033382A1 (en) * | 2014-08-27 | 2016-03-03 | Capnia, Inc. | Methods for immune globulin administration |
| MA41115A (fr) | 2014-12-02 | 2017-10-10 | Biogen Int Neuroscience Gmbh | Procédé de traitement de la maladie d'alzheimer |
| JP6789579B2 (ja) * | 2015-09-10 | 2020-11-25 | アルジオン， インコーポレイテッド | 特定の患者集団において神経変性障害を処置する方法 |
| CN114019170A (zh) * | 2016-01-20 | 2022-02-08 | 基因泰克公司 | 用于阿尔茨海默氏病的高剂量治疗 |
| HRP20211628T1 (hr) * | 2016-08-18 | 2022-02-04 | Alkahest, Inc. | Frakcije krvne plazme kao tretman za kongitivne poremećaje povezane sa starenjem |
| BR112019022402A2 (pt) * | 2017-04-26 | 2020-05-19 | Alkahest Inc | regime de dosagem para tratamento de comprometimentos cognitivo e motor com plasma sanguíneo e produtos de plasma sanguíneo |
| AU2018308088B2 (en) | 2017-07-25 | 2025-05-29 | Truebinding, Inc. | Treating cancer by blocking the interaction of TIM-3 and its ligand |
| SI3672631T1 (sl) | 2017-08-22 | 2023-06-30 | Biogen Ma Inc. | Farmacevtski sestavki, ki vsebujejo protitelesa proti beta amiloidu |
| FI128916B (en) * | 2018-02-05 | 2021-03-15 | Vetcare Oy | Health-promoting composition and method for its preparation |
| KR102276545B1 (ko) * | 2019-09-05 | 2021-07-15 | 고려대학교 산학협력단 | Ct 영상 기반 부위별 대뇌 피질 수축율 예측 방법 및 장치 |
| NL2024431B1 (en) | 2019-12-11 | 2021-09-07 | Sulfateq Bv | Compounds for treatment of alzheimer’s disease |
| US12281166B2 (en) | 2020-05-26 | 2025-04-22 | Truebinding, Inc. | Methods of treating inflammatory diseases by blocking Galectin-3 |
| CA3198827A1 (en) * | 2020-10-30 | 2022-05-05 | Rush University Medical Center | Intranasal immunotherapy for the treatment of alzheimer's disease |
| EP4472679A1 (en) * | 2022-02-03 | 2024-12-11 | Eli Lilly and Company | Regional tau imaging for diagnosing and treating alzheimer's disease |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE348942B (enExample) | 1970-06-02 | 1972-09-18 | Statens Bakteriologiska Labor | |
| US5624898A (en) | 1989-12-05 | 1997-04-29 | Ramsey Foundation | Method for administering neurologic agents to the brain |
| US6585957B1 (en) | 2000-01-25 | 2003-07-01 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
| WO2003028668A2 (en) | 2001-10-04 | 2003-04-10 | Protein Therapeutics, Inc. | Gammaglobulin treatment of immune disorders |
| US20090136505A1 (en) | 2005-02-23 | 2009-05-28 | Johanna Bentz | Intranasal Administration of Active Agents to the Central Nervous System |
| WO2006091332A2 (en) | 2005-02-23 | 2006-08-31 | Alza Corporation | Intranasal administration of active agents to the central nervous system |
| PL1981540T3 (pl) * | 2006-01-30 | 2013-08-30 | Grifols Therapeutics Inc | Sposób leczenia i profilaktyki chorób związanych z odkładaniem się amyloidu z zastosowaniem IgM |
| JO3076B1 (ar) * | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
| TWI489994B (zh) | 2008-03-17 | 2015-07-01 | Baxter Healthcare Sa | 供免疫球蛋白及玻尿酸酶之皮下投藥之用的組合及方法 |
| US9084743B2 (en) | 2009-09-17 | 2015-07-21 | Baxter International Inc. | Stable co-formulation of hyaluronidase and immunoglobulin, and methods of use thereof |
| US8622993B2 (en) | 2009-12-18 | 2014-01-07 | Healthpartners Research Foundation | Device and method for delivering therapeutic substances to the maxillary sinus of a patient |
| SG184820A1 (en) * | 2010-04-13 | 2012-11-29 | Baxter Int | Use of ventricular enlargement rate in intravenous immunoglobulin treatment of alzheimer's disease |
| WO2011142778A1 (en) * | 2010-05-13 | 2011-11-17 | The University Of Kentucky Research Foundation | Treatment of mci and alzheimer's disease |
| JP6055412B2 (ja) * | 2010-09-17 | 2016-12-27 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のｐＨにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
| KR20130139153A (ko) * | 2011-01-18 | 2013-12-20 | 백스터 인터내셔널 인코포레이티드 | 인간 혈액 중 항-베타 아밀로이드 항체의 측정 |
| US20120251524A1 (en) * | 2011-04-01 | 2012-10-04 | Baxter Healthcare S.A. | Use of cytokine levels in intravenous immunoglobulin treatment of alzheimer's disease |
| ES2714999T3 (es) * | 2011-09-24 | 2019-05-31 | Csl Behring Gmbh | Terapia de combinación que usa inmunoglobulina e inhibidor de C1 |
-
2014
- 2014-05-05 AU AU2014262890A patent/AU2014262890B2/en active Active
- 2014-05-05 EP EP14730660.9A patent/EP2994160B1/en active Active
- 2014-05-05 ES ES14730660T patent/ES2740127T3/es active Active
- 2014-05-05 PL PL14730660T patent/PL2994160T3/pl unknown
- 2014-05-05 WO PCT/US2014/036848 patent/WO2014182631A1/en not_active Ceased
- 2014-05-05 LT LTEP14730660.9T patent/LT2994160T/lt unknown
- 2014-05-05 HR HRP20191383TT patent/HRP20191383T1/hr unknown
- 2014-05-05 US US14/270,192 patent/US20140328856A1/en not_active Abandoned
- 2014-05-05 JP JP2016512995A patent/JP6424210B2/ja active Active
- 2014-05-05 HU HUE14730660 patent/HUE044737T2/hu unknown
- 2014-05-05 EP EP19175106.4A patent/EP3552624A1/en active Pending
- 2014-05-05 DK DK14730660.9T patent/DK2994160T3/da active
- 2014-05-05 PT PT14730660T patent/PT2994160T/pt unknown
-
2019
- 2019-01-14 US US16/247,141 patent/US20190144530A1/en not_active Abandoned
- 2019-04-09 AU AU2019202459A patent/AU2019202459B2/en active Active
-
2020
- 2020-10-19 AU AU2020257034A patent/AU2020257034A1/en not_active Abandoned
-
2021
- 2021-04-19 US US17/234,658 patent/US20210238267A1/en not_active Abandoned
-
2024
- 2024-02-19 AU AU2024201051A patent/AU2024201051A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014262890A1 (en) | 2015-11-26 |
| PL2994160T3 (pl) | 2019-10-31 |
| JP6424210B2 (ja) | 2018-11-14 |
| AU2019202459A1 (en) | 2019-05-02 |
| AU2024201051A1 (en) | 2024-03-14 |
| HRP20191383T1 (hr) | 2020-02-07 |
| LT2994160T (lt) | 2019-08-26 |
| DK2994160T3 (da) | 2019-08-12 |
| US20140328856A1 (en) | 2014-11-06 |
| US20210238267A1 (en) | 2021-08-05 |
| EP2994160B1 (en) | 2019-07-03 |
| AU2020257034A1 (en) | 2020-11-12 |
| WO2014182631A1 (en) | 2014-11-13 |
| EP3552624A1 (en) | 2019-10-16 |
| EP2994160A1 (en) | 2016-03-16 |
| AU2014262890B2 (en) | 2019-01-31 |
| JP2016518411A (ja) | 2016-06-23 |
| US20190144530A1 (en) | 2019-05-16 |
| HUE044737T2 (hu) | 2019-11-28 |
| AU2019202459B2 (en) | 2020-07-23 |
| PT2994160T (pt) | 2019-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2740127T3 (es) | Tratamiento de subpoblaciones con enfermedad de Alzheimer con inmunoglobulina G combinada | |
| US11851481B2 (en) | Treatment of central nervous system disorders by intranasal administration of immunoglobulin g | |
| AU2021200093B2 (en) | Treatment and prevention of alzheimer's disease (ad) | |
| US20240148782A1 (en) | Treatment and prevention of alzheimer's disease (ad) | |
| HK40015677A (en) | Treatment of alzheimer's disease subpopulations with pooled immunoglobulin g |