JP2009510084A - 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 - Google Patents
自己免疫及び神経変性疾患及び障害のためのエストリオール療法 Download PDFInfo
- Publication number
- JP2009510084A JP2009510084A JP2008533586A JP2008533586A JP2009510084A JP 2009510084 A JP2009510084 A JP 2009510084A JP 2008533586 A JP2008533586 A JP 2008533586A JP 2008533586 A JP2008533586 A JP 2008533586A JP 2009510084 A JP2009510084 A JP 2009510084A
- Authority
- JP
- Japan
- Prior art keywords
- treatment
- disease
- mice
- eae
- estriol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 101
- 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 title claims abstract description 67
- 229960001348 estriol Drugs 0.000 title claims abstract description 67
- 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 title claims abstract description 62
- 208000015122 neurodegenerative disease Diseases 0.000 title claims abstract description 39
- 230000004770 neurodegeneration Effects 0.000 title claims abstract description 30
- 208000035475 disorder Diseases 0.000 title claims abstract description 8
- 230000001363 autoimmune Effects 0.000 title abstract description 8
- 208000023275 Autoimmune disease Diseases 0.000 title description 41
- 238000002560 therapeutic procedure Methods 0.000 title description 13
- 201000010099 disease Diseases 0.000 claims abstract description 88
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 67
- 239000000262 estrogen Substances 0.000 claims abstract description 65
- 229940011871 estrogen Drugs 0.000 claims abstract description 65
- 208000024891 symptom Diseases 0.000 claims abstract description 53
- 108010038795 estrogen receptors Proteins 0.000 claims abstract description 26
- 239000012190 activator Substances 0.000 claims abstract description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 208000006011 Stroke Diseases 0.000 claims abstract description 5
- 201000011240 Frontotemporal dementia Diseases 0.000 claims abstract description 4
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 4
- 208000024777 Prion disease Diseases 0.000 claims abstract description 3
- 102000015694 estrogen receptors Human genes 0.000 claims abstract description 3
- 238000011282 treatment Methods 0.000 claims description 307
- 239000003795 chemical substances by application Substances 0.000 claims description 88
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 80
- 229960005309 estradiol Drugs 0.000 claims description 69
- 229930182833 estradiol Natural products 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 49
- 230000035935 pregnancy Effects 0.000 claims description 46
- 230000002829 reductive effect Effects 0.000 claims description 45
- 230000003247 decreasing effect Effects 0.000 claims description 38
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 37
- 208000016192 Demyelinating disease Diseases 0.000 claims description 31
- 206010012305 Demyelination Diseases 0.000 claims description 31
- 239000002552 dosage form Substances 0.000 claims description 21
- 210000002966 serum Anatomy 0.000 claims description 19
- 229960003387 progesterone Drugs 0.000 claims description 18
- 239000000186 progesterone Substances 0.000 claims description 18
- 230000001537 neural effect Effects 0.000 claims description 14
- 230000003376 axonal effect Effects 0.000 claims description 13
- 230000001747 exhibiting effect Effects 0.000 claims description 10
- 125000000251 estriol group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 229960003399 estrone Drugs 0.000 claims description 6
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 claims description 5
- 239000003862 glucocorticoid Substances 0.000 claims description 5
- 208000014644 Brain disease Diseases 0.000 claims description 4
- 208000032274 Encephalopathy Diseases 0.000 claims description 4
- 229940123177 Estrogen receptor beta agonist Drugs 0.000 claims description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 4
- 230000005856 abnormality Effects 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 231100000331 toxic Toxicity 0.000 claims description 4
- 230000002588 toxic effect Effects 0.000 claims description 4
- 210000001185 bone marrow Anatomy 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010061296 Motor dysfunction Diseases 0.000 claims description 2
- 206010034010 Parkinsonism Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 230000003412 degenerative effect Effects 0.000 claims description 2
- 229960003836 estriol succinate Drugs 0.000 claims description 2
- 125000003719 estrone group Chemical group 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 230000002503 metabolic effect Effects 0.000 claims description 2
- 230000000626 neurodegenerative effect Effects 0.000 claims description 2
- 229940053934 norethindrone Drugs 0.000 claims description 2
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical group O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229960003604 testosterone Drugs 0.000 claims description 2
- 230000001990 hyperexcitatory effect Effects 0.000 claims 2
- 239000002148 ERα-agonist Substances 0.000 claims 1
- VGHIBOFCBWMZNZ-ZXXIGWHRSA-N NS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 Chemical compound NS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 VGHIBOFCBWMZNZ-ZXXIGWHRSA-N 0.000 claims 1
- 208000010886 Peripheral nerve injury Diseases 0.000 claims 1
- 208000029028 brain injury Diseases 0.000 claims 1
- 210000001525 retina Anatomy 0.000 claims 1
- 239000003270 steroid hormone Substances 0.000 abstract description 10
- 241000124008 Mammalia Species 0.000 abstract description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 abstract description 2
- 108010023813 estriol receptor Proteins 0.000 abstract 1
- 201000002491 encephalomyelitis Diseases 0.000 description 221
- 241000699670 Mus sp. Species 0.000 description 218
- 239000003446 ligand Substances 0.000 description 135
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 129
- 239000003981 vehicle Substances 0.000 description 124
- 108010041356 Estrogen Receptor beta Proteins 0.000 description 108
- IOTXSIGGFRQYKW-UHFFFAOYSA-N 4,4',4''-(4-propylpyrazole-1,3,5-triyl)trisphenol Chemical compound CCCC=1C(C=2C=CC(O)=CC=2)=NN(C=2C=CC(O)=CC=2)C=1C1=CC=C(O)C=C1 IOTXSIGGFRQYKW-UHFFFAOYSA-N 0.000 description 98
- 102000007594 Estrogen Receptor alpha Human genes 0.000 description 90
- 102000000509 Estrogen Receptor beta Human genes 0.000 description 90
- 150000008364 diarylpropionitriles Chemical class 0.000 description 74
- 210000000278 spinal cord Anatomy 0.000 description 69
- 102100038595 Estrogen receptor Human genes 0.000 description 62
- 210000004885 white matter Anatomy 0.000 description 56
- 230000000694 effects Effects 0.000 description 51
- 210000004027 cell Anatomy 0.000 description 49
- 210000004884 grey matter Anatomy 0.000 description 44
- 238000010186 staining Methods 0.000 description 44
- 230000003902 lesion Effects 0.000 description 34
- 230000001404 mediated effect Effects 0.000 description 34
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 33
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 33
- 230000007423 decrease Effects 0.000 description 33
- 206010061218 Inflammation Diseases 0.000 description 29
- 230000006698 induction Effects 0.000 description 29
- 230000004054 inflammatory process Effects 0.000 description 29
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 210000003050 axon Anatomy 0.000 description 26
- 238000002474 experimental method Methods 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 22
- 210000000115 thoracic cavity Anatomy 0.000 description 21
- 238000001727 in vivo Methods 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 20
- 230000004044 response Effects 0.000 description 20
- 102100029951 Estrogen receptor beta Human genes 0.000 description 19
- 102000006386 Myelin Proteins Human genes 0.000 description 19
- 108010083674 Myelin Proteins Proteins 0.000 description 19
- 210000005012 myelin Anatomy 0.000 description 19
- 238000011813 knockout mouse model Methods 0.000 description 18
- 102000004127 Cytokines Human genes 0.000 description 17
- 108090000695 Cytokines Proteins 0.000 description 17
- 102000008763 Neurofilament Proteins Human genes 0.000 description 17
- 108010088373 Neurofilament Proteins Proteins 0.000 description 17
- 210000005044 neurofilament Anatomy 0.000 description 17
- 210000002569 neuron Anatomy 0.000 description 16
- 230000000324 neuroprotective effect Effects 0.000 description 16
- 239000013641 positive control Substances 0.000 description 16
- 238000011002 quantification Methods 0.000 description 16
- 150000003431 steroids Chemical class 0.000 description 16
- 230000016396 cytokine production Effects 0.000 description 15
- 238000012744 immunostaining Methods 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- 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 14
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 14
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 14
- 238000000540 analysis of variance Methods 0.000 description 14
- 230000028993 immune response Effects 0.000 description 14
- 230000006872 improvement Effects 0.000 description 14
- 238000002595 magnetic resonance imaging Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 102000047918 Myelin Basic Human genes 0.000 description 12
- 101710107068 Myelin basic protein Proteins 0.000 description 12
- 101710202239 Tubulin beta-3 chain Proteins 0.000 description 12
- 230000003110 anti-inflammatory effect Effects 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 11
- 239000000556 agonist Substances 0.000 description 11
- 238000002203 pretreatment Methods 0.000 description 11
- 230000004224 protection Effects 0.000 description 11
- 230000005951 type IV hypersensitivity Effects 0.000 description 11
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 11
- 108010072051 Glatiramer Acetate Proteins 0.000 description 10
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 230000001681 protective effect Effects 0.000 description 10
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 9
- 108010002616 Interleukin-5 Proteins 0.000 description 9
- 102000000743 Interleukin-5 Human genes 0.000 description 9
- 230000009286 beneficial effect Effects 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 108010074328 Interferon-gamma Proteins 0.000 description 8
- 102000004889 Interleukin-6 Human genes 0.000 description 8
- 108090001005 Interleukin-6 Proteins 0.000 description 8
- 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 8
- 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 229940088597 hormone Drugs 0.000 description 8
- 239000005556 hormone Substances 0.000 description 8
- 238000010254 subcutaneous injection Methods 0.000 description 8
- 239000007929 subcutaneous injection Substances 0.000 description 8
- 229910052688 Gadolinium Inorganic materials 0.000 description 7
- 102000008070 Interferon-gamma Human genes 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 229940038717 copaxone Drugs 0.000 description 7
- 208000033068 episodic angioedema with eosinophilia Diseases 0.000 description 7
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 7
- 229960003130 interferon gamma Drugs 0.000 description 7
- 210000000274 microglia Anatomy 0.000 description 7
- 229940127234 oral contraceptive Drugs 0.000 description 7
- 239000003539 oral contraceptive agent Substances 0.000 description 7
- 230000000770 proinflammatory effect Effects 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 230000007480 spreading Effects 0.000 description 7
- 238000003892 spreading Methods 0.000 description 7
- 210000004291 uterus Anatomy 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000001135 Friedman test Methods 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 230000008512 biological response Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 230000007171 neuropathology Effects 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 201000004569 Blindness Diseases 0.000 description 5
- LUWJPTVQOMUZLW-UHFFFAOYSA-N Luxol fast blue MBS Chemical compound [Cu++].Cc1ccccc1N\C(N)=N\c1ccccc1C.Cc1ccccc1N\C(N)=N\c1ccccc1C.OS(=O)(=O)c1cccc2c3nc(nc4nc([n-]c5[n-]c(nc6nc(n3)c3ccccc63)c3c(cccc53)S(O)(=O)=O)c3ccccc43)c12 LUWJPTVQOMUZLW-UHFFFAOYSA-N 0.000 description 5
- 206010033799 Paralysis Diseases 0.000 description 5
- 206010043376 Tetanus Diseases 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 230000003190 augmentative effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 101150107911 eae gene Proteins 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000003364 immunohistochemistry Methods 0.000 description 5
- 210000004969 inflammatory cell Anatomy 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000000653 nervous system Anatomy 0.000 description 5
- 230000027758 ovulation cycle Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000004393 visual impairment Effects 0.000 description 5
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 4
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 208000004044 Hypesthesia Diseases 0.000 description 4
- 108010005716 Interferon beta-1a Proteins 0.000 description 4
- 108010005714 Interferon beta-1b Proteins 0.000 description 4
- 108090000467 Interferon-beta Proteins 0.000 description 4
- 102000003996 Interferon-beta Human genes 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 4
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 230000002357 endometrial effect Effects 0.000 description 4
- 208000028327 extreme fatigue Diseases 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000034783 hypoesthesia Diseases 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 229960002725 isoflurane Drugs 0.000 description 4
- 208000018769 loss of vision Diseases 0.000 description 4
- 231100000864 loss of vision Toxicity 0.000 description 4
- 230000007659 motor function Effects 0.000 description 4
- 231100000862 numbness Toxicity 0.000 description 4
- 238000009806 oophorectomy Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000032696 parturition Effects 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000011268 retreatment Methods 0.000 description 4
- 238000010825 rotarod performance test Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 210000004988 splenocyte Anatomy 0.000 description 4
- MQIMZDXIAHJKQP-UHFFFAOYSA-N 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol Chemical compound N=1C2=CC(O)=CC(C=C)=C2OC=1C1=CC=C(O)C(F)=C1 MQIMZDXIAHJKQP-UHFFFAOYSA-N 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 3
- 108010010974 Proteolipids Proteins 0.000 description 3
- 102000016202 Proteolipids Human genes 0.000 description 3
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 108090000704 Tubulin Proteins 0.000 description 3
- 102000004243 Tubulin Human genes 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000006472 autoimmune response Effects 0.000 description 3
- 229940003504 avonex Drugs 0.000 description 3
- 229940021459 betaseron Drugs 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000001739 density measurement Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000009699 differential effect Effects 0.000 description 3
- 210000004696 endometrium Anatomy 0.000 description 3
- 229960003776 glatiramer acetate Drugs 0.000 description 3
- 239000003163 gonadal steroid hormone Substances 0.000 description 3
- 230000003054 hormonal effect Effects 0.000 description 3
- 230000004727 humoral immunity Effects 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960001810 meprednisone Drugs 0.000 description 3
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 229960004618 prednisone Drugs 0.000 description 3
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000003637 steroidlike Effects 0.000 description 3
- 229940037128 systemic glucocorticoids Drugs 0.000 description 3
- MCYMLYCMBFUHBL-UHFFFAOYSA-N 4-(1h-indol-2-yl)benzene-1,3-dicarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=CC(C(=N)N)=CC=C1C1=CC2=CC=CC=C2N1 MCYMLYCMBFUHBL-UHFFFAOYSA-N 0.000 description 2
- LHYQAEFVHIZFLR-UHFFFAOYSA-L 4-(4-diazonio-3-methoxyphenyl)-2-methoxybenzenediazonium;dichloride Chemical compound [Cl-].[Cl-].C1=C([N+]#N)C(OC)=CC(C=2C=C(OC)C([N+]#N)=CC=2)=C1 LHYQAEFVHIZFLR-UHFFFAOYSA-L 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 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 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 206010022004 Influenza like illness Diseases 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 101710116771 Lysosome-associated membrane glycoprotein 2 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 206010072731 White matter lesion Diseases 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000002025 microglial effect Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 210000003007 myelin sheath Anatomy 0.000 description 2
- 229960005027 natalizumab Drugs 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 238000002610 neuroimaging Methods 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000008823 permeabilization Effects 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102100024341 10 kDa heat shock protein, mitochondrial Human genes 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- JFUAWXPBHXKZGA-IBGZPJMESA-N 4-fluoro-2-[(4r)-5,5,5-trifluoro-4-hydroxy-2-methyl-4-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-yl]phenol Chemical compound C([C@@](O)(CC=1NC2=CN=CC=C2C=1)C(F)(F)F)C(C)(C)C1=CC(F)=CC=C1O JFUAWXPBHXKZGA-IBGZPJMESA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010068051 Chimerism Diseases 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100025537 ERI1 exoribonuclease 3 Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101001056896 Homo sapiens ERI1 exoribonuclease 3 Proteins 0.000 description 1
- 101001010910 Homo sapiens Estrogen receptor beta Proteins 0.000 description 1
- 101000604993 Homo sapiens Lysosome-associated membrane glycoprotein 2 Proteins 0.000 description 1
- 101000848653 Homo sapiens Tripartite motif-containing protein 26 Proteins 0.000 description 1
- 206010021002 Hypoglycaemic encephalopathy Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 208000034702 Multiple pregnancies Diseases 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 101000708422 Podarcis siculus Tissue- and phase-specific nuclear protein Proteins 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 229940121912 Progesterone receptor agonist Drugs 0.000 description 1
- 229940123788 Progesterone receptor antagonist Drugs 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 238000009171 T-cell vaccination Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010043994 Tonic convulsion Diseases 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- ZOVABFBGAYSQTL-AECPDVIXSA-N [(8r,9s,13s,14s,16r,17r)-3-hexanoyloxy-16-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] hexanoate Chemical compound C1CC2=CC(OC(=O)CCCCC)=CC=C2[C@@H]2[C@@H]1[C@@H]1C[C@@H](O)[C@H](OC(=O)CCCCC)[C@@]1(C)CC2 ZOVABFBGAYSQTL-AECPDVIXSA-N 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002502 anti-myelin effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 201000004982 autoimmune uveitis Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- -1 cyclosporin A) ) Chemical compound 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 108010046025 early pregnancy factor Proteins 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002166 estriols Chemical class 0.000 description 1
- 238000009164 estrogen replacement therapy Methods 0.000 description 1
- 150000002167 estrones Chemical class 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- HZHFFEYYPYZMNU-UHFFFAOYSA-K gadodiamide Chemical compound [Gd+3].CNC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC(=O)NC HZHFFEYYPYZMNU-UHFFFAOYSA-K 0.000 description 1
- 229940124750 glucocorticoid receptor agonist Drugs 0.000 description 1
- 229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 102000046101 human AFP Human genes 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000009802 hysterectomy Methods 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 229960004461 interferon beta-1a Drugs 0.000 description 1
- 229960003161 interferon beta-1b Drugs 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 230000017307 interleukin-4 production Effects 0.000 description 1
- 230000022023 interleukin-5 production Effects 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 230000007991 neuronal integrity Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000002661 non steroidal estrogen Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 108091008589 nuclear estrogen receptors Proteins 0.000 description 1
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 229940087854 solu-medrol Drugs 0.000 description 1
- VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 description 1
- 229960000488 tizanidine Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229940079023 tysabri Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000001836 utereotrophic effect Effects 0.000 description 1
- 230000002477 vacuolizing effect Effects 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000011816 wild-type C57Bl6 mouse Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/34—Gestagens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/40—Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72097205P | 2005-09-26 | 2005-09-26 | |
| US83352706P | 2006-07-26 | 2006-07-26 | |
| PCT/US2006/037752 WO2007038636A2 (en) | 2005-09-26 | 2006-09-26 | Estriol therapy for autoimmune and neurodegenerataive diseases and disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009510084A true JP2009510084A (ja) | 2009-03-12 |
| JP2009510084A5 JP2009510084A5 (enExample) | 2011-01-27 |
Family
ID=37900442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008533586A Pending JP2009510084A (ja) | 2005-09-26 | 2006-09-26 | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 |
Country Status (5)
| Country | Link |
|---|---|
| EP (3) | EP1929291A4 (enExample) |
| JP (1) | JP2009510084A (enExample) |
| AU (1) | AU2006294662A1 (enExample) |
| CA (1) | CA2623839C (enExample) |
| WO (1) | WO2007038636A2 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009510070A (ja) * | 2005-09-26 | 2009-03-12 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 |
| JP2014508809A (ja) * | 2011-03-22 | 2014-04-10 | ザ・ポピュレイション・カウンシル，インコーポレイテッド | アンドロゲンを用いたミエリン再生 |
| JPWO2015199195A1 (ja) * | 2014-06-27 | 2017-04-20 | 国立大学法人名古屋大学 | 標本作製用包埋剤、硬化性基材非浸透標本の作製方法、硬化性基材浸透標本の作製方法、硬化性基材非浸透標本、凍結包埋剤の薄切性改善剤、及び凍結包埋剤 |
| JP2019526612A (ja) * | 2016-09-12 | 2019-09-19 | スティーブン・ホフマン | 認知症を治療するための組成物 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6936599B2 (en) | 2001-04-25 | 2005-08-30 | The Regents Of The University Of California | Estriol therapy for multiple sclerosis and other autoimmune diseases |
| US20130203722A1 (en) | 2006-09-26 | 2013-08-08 | Rhonda R. Voskuhl | Estriol therapy for autoimmune and neurodegenerative disease and disorders |
| WO2010050916A1 (en) * | 2008-10-31 | 2010-05-06 | The Regents Of The University Of California | Estrogen receptor ligand treatment for neurodegenerative diseases |
| EP2164498A4 (en) * | 2007-06-04 | 2010-09-08 | Univ California | PREGNANCY HORMONE ASSOCIATION FOR THE TREATMENT OF AUTOIMMUNE DISEASES |
| US20100239528A1 (en) * | 2007-07-20 | 2010-09-23 | Stem Cell Therapeutics Corp. | Treating or Ameliorating a Neuroinflammatory or Demyelinating Disorder with Prolactin and Interferon-Beta |
| CA2700210C (en) | 2007-10-26 | 2015-12-22 | Acadia Pharmaceuticals Inc. | Condensed compounds with activity at estrogen receptors |
| HUP0800414A2 (en) * | 2008-07-04 | 2010-10-28 | Pecsi Tudomanyegyetem | Pharmaceutical combination |
| US9808470B2 (en) | 2012-04-19 | 2017-11-07 | Universite De Liege | Estrogenic components for use in the treatment of neurological disorders |
| EP2653163A1 (en) * | 2012-04-19 | 2013-10-23 | Université de Liège | Estrogenic components for use in the treatment of neurological disorders |
| WO2015168000A1 (en) | 2014-04-28 | 2015-11-05 | The Regents Of The University Of California | Estrogen combination for treatment of multiple sclerosis |
| WO2015168002A1 (en) | 2014-04-28 | 2015-11-05 | The Regents Of The University Of California | Pharmaceutical packaging for estriol therapy |
| WO2016036719A1 (en) | 2014-09-02 | 2016-03-10 | The Regents Of The University Of California | Estrogen therapy for brain gray matter atrophy and associated disability |
| EP3189026B1 (en) * | 2014-09-02 | 2020-07-22 | The Regents of The University of California | Estrogen receptor ligand treatment for neurodegenerative diseases |
| WO2016053946A1 (en) | 2014-09-29 | 2016-04-07 | The Regents Of The University Of California | Compositions and methods for maintaining cognitive function |
| WO2016160832A1 (en) | 2015-03-30 | 2016-10-06 | The Regents Of The University Of California | Methods of monitoring estriol therapy |
| EP3541279B1 (en) * | 2016-11-15 | 2023-09-06 | The Regents of the University of California | Apparatuses for improving peripheral nerve function |
| EP3787633A1 (en) | 2018-05-02 | 2021-03-10 | Pantarhei Oncology B.V. | Treatment of advanced estrogen receptor positive breast cancer |
| TW202124418A (zh) * | 2019-12-20 | 2021-07-01 | 比利時商埃斯特拉有限責任公司 | 壞死性凋亡調節劑、篩選方法及醫藥組成物 |
| CN113243332B (zh) * | 2020-02-07 | 2023-07-28 | 上海市东方医院（同济大学附属东方医院） | 一种广泛脑区神经元树突发育障碍动物模型的制备与应用 |
| US12186564B2 (en) | 2021-02-09 | 2025-01-07 | The Regents Of The University Of California | Methods and apparatuses for treating stroke using low-frequency stimulation |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11514327A (ja) * | 1993-11-05 | 1999-12-07 | ユニバーシティ・オブ・フロリダ・リサーチ・ファウンデーション・インコーポレーテッド | エストロゲン組成物及び神経保護の方法 |
| US20010016325A1 (en) * | 1999-12-01 | 2001-08-23 | Mobley William C. | Activation of novel estrogen receptor supports and neuronal viability and function |
| WO2002085374A1 (en) * | 2001-04-25 | 2002-10-31 | The Regents Of The University Of California | Estriol therapy for multiple sclerosis and other autoimmune diseases |
| US20020164314A1 (en) * | 2001-03-02 | 2002-11-07 | Neurostasis, Inc. | Ovarian hormone induced neural stem cell increase |
| JP2003522737A (ja) * | 1999-11-05 | 2003-07-29 | ワイエス | アミロイド阻害化合物を同定しそして使用するための方法 |
| JP2003246736A (ja) * | 2002-02-25 | 2003-09-02 | Noritake Co Ltd | 自己免疫疾患発病抑制薬 |
| JP2009510070A (ja) * | 2005-09-26 | 2009-03-12 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9502921D0 (sv) | 1995-08-23 | 1995-08-23 | Astra Ab | New compounds |
| US6734211B1 (en) * | 1999-07-09 | 2004-05-11 | Oregon Health & Sciences University | Compositions and methods for promoting nerve regeneration |
| US20050209208A1 (en) * | 2001-04-25 | 2005-09-22 | The Regents Of The University Of California | Use of estriol and other estranes, estrogens and estrogen receptor active compositions in the treatment of psoriasis and other autoimmune disorders |
| EP1358881A1 (en) * | 2002-04-30 | 2003-11-05 | Schering Aktiengesellschaft | Use of biogenic estriol diester prodrugs for the treatment of autoimmune diseases |
-
2006
- 2006-09-26 EP EP06815626A patent/EP1929291A4/en not_active Ceased
- 2006-09-26 CA CA2623839A patent/CA2623839C/en not_active Expired - Fee Related
- 2006-09-26 EP EP16000349.7A patent/EP3045177A1/en not_active Withdrawn
- 2006-09-26 AU AU2006294662A patent/AU2006294662A1/en not_active Abandoned
- 2006-09-26 WO PCT/US2006/037752 patent/WO2007038636A2/en not_active Ceased
- 2006-09-26 JP JP2008533586A patent/JP2009510084A/ja active Pending
- 2006-09-26 EP EP13005320.0A patent/EP2698167A3/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11514327A (ja) * | 1993-11-05 | 1999-12-07 | ユニバーシティ・オブ・フロリダ・リサーチ・ファウンデーション・インコーポレーテッド | エストロゲン組成物及び神経保護の方法 |
| JP2003522737A (ja) * | 1999-11-05 | 2003-07-29 | ワイエス | アミロイド阻害化合物を同定しそして使用するための方法 |
| US20010016325A1 (en) * | 1999-12-01 | 2001-08-23 | Mobley William C. | Activation of novel estrogen receptor supports and neuronal viability and function |
| US20020164314A1 (en) * | 2001-03-02 | 2002-11-07 | Neurostasis, Inc. | Ovarian hormone induced neural stem cell increase |
| WO2002085374A1 (en) * | 2001-04-25 | 2002-10-31 | The Regents Of The University Of California | Estriol therapy for multiple sclerosis and other autoimmune diseases |
| JP2003246736A (ja) * | 2002-02-25 | 2003-09-02 | Noritake Co Ltd | 自己免疫疾患発病抑制薬 |
| JP2009510070A (ja) * | 2005-09-26 | 2009-03-12 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 |
Non-Patent Citations (8)
| Title |
|---|
| JPN5007024041; ＫＩＭ Ｓ: ＮＥＵＲＯＬＯＧＹ Ｖｏｌ．５２ Ｎｏ．１, 19990412, ｐｐ．１２３０-１２３８, ＬＩＰＰＩＮＣＯＴＴ ＷＩＬＬＩＡＭＳ ＆ ＷＩＬＫＩＮＳ * |
| JPN5008015192; ＳＯＬＤＡＮ: ＴＨＥ ＪＯＵＲＮＡＬ ＯＦ ＩＭＭＵＮＯＬＯＧＹ Ｖｏｌ．１７１ Ｎｏ．１１, 200312, ｐｐ．６２６７-６２７４ * |
| JPN6012025498; Ｏｆｆｎｅｒ Ｈ: 'Ｎｅｕｒｏｉｍｍｕｎｏｐｒｏｔｅｃｔｉｖｅ ｅｆｆｅｃｔｓ ｏｆ ｅｓｔｒｏｇｅｎ ａｎｄ ｄｅｒｉｖａｔｉｖｅｓ ｉｎ ｅｘｐｅｒｉｍｅｎｔａｌ ａｕｔｏｉｍｍｕｎｅ ｅｎｃｅｐｈａｌｏｍｙｅｌｉｔ' Ｊ Ｎｅｕｒｏｓｃｉ Ｒｅｓ． Ｖｏｌ．７８ Ｎｏ．５, 20041201, ｐｐ．６０３-６２４ * |
| JPN6012025501; Ｋｕｒｍａｎ ＲＪ ｅｔ ａｌ．: 'Ｎｏｒｅｔｈｉｎｄｒｏｎｅ ａｃｅｔａｔｅ ａｎｄ ｅｓｔｒａｄｉｏｌ-ｉｎｄｕｃｅｄ ｅｎｄｏｍｅｔｒｉａｌ ｈｙｐｅｒｐｌａｓｉａ．' Ｏｂｓｔｅｔ Ｇｙｎｅｃｏｌ． Ｖｏｌ．９６ Ｎｏ．３, 200009, ｐｐ．３７３-３７９ * |
| JPN6012025504; メルクマニュアル日本語版 第１７版, 19991210, ｐｐ．１４７７-１４７９, 日経ＢＰ社 * |
| JPN6012025507; Ｋｕｉｐｅｒ ＧＧ ｅｔ ａｌ．: 'Ｃｏｍｐａｒｉｓｏｎ ｏｆ ｔｈｅ ｌｉｇａｎｄ ｂｉｎｄｉｎｇ ｓｐｅｃｉｆｉｃｉｔｙ ａｎｄ ｔｒａｎｓｃｒｉｐｔ ｔｉｓｓｕｅ ｄｉｓｔｒｉｂｕｔｉｏｎ ｏｆ ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ' Ｅｎｄｏｃｒｉｎｏｌｏｇｙ Ｖｏｌ．１３８ Ｎｏ．３, 199703, ｐｐ．８６３-８７０ * |
| JPN6013005494; Ｈａｒｒｉｎｇｔｏｎ ＷＲ ｅｔ ａｌ．: 'Ａｃｔｉｖｉｔｉｅｓ ｏｆ ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ ａｌｐｈａ- ａｎｄ ｂｅｔａ-ｓｅｌｅｃｔｉｖｅ ｌｉｇａｎｄｓ ａｔ ｄｉｖｅｒｓｅ ｅｓｔｒｏｇｅｎ ｒｅｓｐｏｎｓｉｖｅ ｇｅｎ' Ｍｏｌ Ｃｅｌｌ Ｅｎｄｏｃｒｉｎｏｌ． Ｖｏｌ．２０６ Ｎｏ．１-２, 20030829, ｐｐ．１３-２２ * |
| JPN6013005495; Ｃａｒｓｗｅｌｌ ＨＶ ｅｔ ａｌ．: 'Ｎｅｕｒｏｐｒｏｔｅｃｔｉｏｎ ｂｙ ａ ｓｅｌｅｃｔｉｖｅ ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ ｂｅｔａ ａｇｏｎｉｓｔ ｉｎ ａ ｍｏｕｓｅ ｍｏｄｅｌ ｏｆ ｇｌｏｂａｌ ｉｓｃｈｅｍｉａ．' Ａｍ Ｊ Ｐｈｙｓｉｏｌ Ｈｅａｒｔ Ｃｉｒｃ Ｐｈｙｓｉｏｌ． Ｖｏｌ．２８７ Ｎｏ．４, 20040520, ｐｐ．１５０１-１５０４ * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009510070A (ja) * | 2005-09-26 | 2009-03-12 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 |
| JP2014508809A (ja) * | 2011-03-22 | 2014-04-10 | ザ・ポピュレイション・カウンシル，インコーポレイテッド | アンドロゲンを用いたミエリン再生 |
| US9364488B2 (en) | 2011-03-22 | 2016-06-14 | The Population Council, Inc. | Myelin regeneration with androgens |
| JPWO2015199195A1 (ja) * | 2014-06-27 | 2017-04-20 | 国立大学法人名古屋大学 | 標本作製用包埋剤、硬化性基材非浸透標本の作製方法、硬化性基材浸透標本の作製方法、硬化性基材非浸透標本、凍結包埋剤の薄切性改善剤、及び凍結包埋剤 |
| JP2019526612A (ja) * | 2016-09-12 | 2019-09-19 | スティーブン・ホフマン | 認知症を治療するための組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007038636A3 (en) | 2007-12-27 |
| EP3045177A1 (en) | 2016-07-20 |
| EP2698167A2 (en) | 2014-02-19 |
| EP2698167A3 (en) | 2014-03-05 |
| EP1929291A4 (en) | 2010-12-22 |
| EP1929291A2 (en) | 2008-06-11 |
| CA2623839C (en) | 2013-12-17 |
| AU2006294662A1 (en) | 2007-04-05 |
| CA2623839A1 (en) | 2007-04-05 |
| WO2007038636A2 (en) | 2007-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009510084A (ja) | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 | |
| US9168262B2 (en) | Estriol therapy for multiple sclerosis and other autoimmune diseases | |
| US10610535B2 (en) | Diarylpropionitrile therapy for treatment of multiple sclerosis | |
| US20090131385A1 (en) | Estriol Therapy for Autoimmune and Neurodegenerative Diseases and Disorders | |
| US9452175B2 (en) | Pregnancy hormone combination for treatment of autoimmune diseases | |
| Sicotte et al. | Treatment of multiple sclerosis with the pregnancy hormone estriol | |
| US20210137943A1 (en) | Estrogen combination for treatment of multiple sclerosis | |
| US20110236350A1 (en) | Estrogen receptor ligand treatment for neurodegenerative diseases | |
| WO2006053172A2 (en) | The use of estriol and other estranes, estrogens and estrogen receptor active compositions in the treatment of psoriasis and other autoimmune diseases | |
| US20110256096A1 (en) | Estrogen receptor ligand and/or interferon beta treatment for neurodegenerative diseases | |
| JP2009510070A (ja) | 自己免疫及び神経変性疾患及び障害のためのエストリオール療法 | |
| US20090297477A1 (en) | Estriol Therapy for Autoimmune and Neurodegenerative Disease and Disorders | |
| Perdhana et al. | Patients with secondary amenorrhea due to tuberculosis endometritis towards the induced anti-tuberculosis drug category 1 | |
| Du et al. | Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis | |
| Harrison-Woolrych | Breast and pelvic examination in women taking HRT. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090928 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090928 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101130 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110913 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120518 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120817 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120824 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120910 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120918 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120925 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121017 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121024 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121119 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130206 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130430 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130509 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130924 |