JP2019502716A - 神経発達障害療法 - Google Patents
神経発達障害療法 Download PDFInfo
- Publication number
- JP2019502716A JP2019502716A JP2018536130A JP2018536130A JP2019502716A JP 2019502716 A JP2019502716 A JP 2019502716A JP 2018536130 A JP2018536130 A JP 2018536130A JP 2018536130 A JP2018536130 A JP 2018536130A JP 2019502716 A JP2019502716 A JP 2019502716A
- Authority
- JP
- Japan
- Prior art keywords
- syndrome
- mice
- day
- treatment
- disorder
- 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.)
- Granted
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 8
- 208000035475 disorder Diseases 0.000 title description 7
- 238000002560 therapeutic procedure Methods 0.000 title description 3
- 230000007472 neurodevelopment Effects 0.000 title 1
- 208000006289 Rett Syndrome Diseases 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 16
- 208000029560 autism spectrum disease Diseases 0.000 claims abstract description 12
- 208000009575 Angelman syndrome Diseases 0.000 claims abstract description 9
- 201000001388 Smith-Magenis syndrome Diseases 0.000 claims abstract description 7
- 206010049644 Williams syndrome Diseases 0.000 claims abstract description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 7
- 206010008129 cerebral palsy Diseases 0.000 claims abstract description 6
- 208000012202 Pervasive developmental disease Diseases 0.000 claims abstract description 3
- 208000024825 childhood disintegrative disease Diseases 0.000 claims abstract description 3
- AMVCMSPVJGQNFF-UHFFFAOYSA-N 1-(5,5-diphenyloxolan-3-yl)-n,n-dimethylmethanamine Chemical compound C1C(CN(C)C)COC1(C=1C=CC=CC=1)C1=CC=CC=C1 AMVCMSPVJGQNFF-UHFFFAOYSA-N 0.000 claims abstract 2
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 5
- 230000001123 neurodevelopmental effect Effects 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 238000011282 treatment Methods 0.000 abstract description 29
- FEQOLYDPQKHFTD-UHFFFAOYSA-N 1-(2,2-diphenyloxolan-3-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1CCOC1(C=1C=CC=CC=1)C1=CC=CC=C1 FEQOLYDPQKHFTD-UHFFFAOYSA-N 0.000 abstract description 7
- 208000029726 Neurodevelopmental disease Diseases 0.000 abstract description 6
- 241000699670 Mus sp. Species 0.000 description 51
- 239000003981 vehicle Substances 0.000 description 26
- 230000006977 prepulse inhibition Effects 0.000 description 14
- 238000012360 testing method Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 101150083522 MECP2 gene Proteins 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 206010010904 Convulsion Diseases 0.000 description 7
- -1 dextranolphan Chemical compound 0.000 description 7
- 230000007774 longterm Effects 0.000 description 7
- 230000024188 startle response Effects 0.000 description 6
- 102100039124 Methyl-CpG-binding protein 2 Human genes 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- 208000033808 peripheral neuropathy Diseases 0.000 description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 208000016285 Movement disease Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000005021 gait Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 208000019116 sleep disease Diseases 0.000 description 4
- 206010052804 Drug tolerance Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 3
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000026781 habituation Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 208000022925 sleep disturbance Diseases 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- BGKFPRIGXAVYNX-UHFFFAOYSA-N 5,7-dichloro-4-oxo-1H-quinoline-2-carboxylic acid Chemical compound ClC1=CC(Cl)=CC2=NC(C(=O)O)=CC(O)=C21 BGKFPRIGXAVYNX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910052688 Gadolinium Inorganic materials 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000007658 neurological function Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 230000008775 paternal effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000011422 pharmacological therapy Methods 0.000 description 2
- 230000036278 prepulse Effects 0.000 description 2
- 230000001107 psychogenic effect Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000011808 rodent model Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- QEXADSRMRUUCQJ-CABCVRRESA-N (4ar,8ar)-8a-phenyl-2,3,4,4a,5,6,7,8-octahydro-1h-quinoline Chemical compound C1([C@@]23CCCC[C@@H]2CCCN3)=CC=CC=C1 QEXADSRMRUUCQJ-CABCVRRESA-N 0.000 description 1
- DRCWOKJLSQUJPZ-DZGCQCFKSA-N (4ar,9as)-n-ethyl-1,4,9,9a-tetrahydrofluoren-4a-amine Chemical compound C1C2=CC=CC=C2[C@]2(NCC)[C@H]1CC=CC2 DRCWOKJLSQUJPZ-DZGCQCFKSA-N 0.000 description 1
- JQWJJJYHVHNXJH-UHFFFAOYSA-N 1-(1,2-diphenylethyl)piperidine Chemical compound C=1C=CC=CC=1CC(C=1C=CC=CC=1)N1CCCCC1 JQWJJJYHVHNXJH-UHFFFAOYSA-N 0.000 description 1
- MZIQKELNJVAZDS-UHFFFAOYSA-N 1-(5,5-diphenyloxolan-3-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.C1C(CN(C)C)COC1(C=1C=CC=CC=1)C1=CC=CC=C1 MZIQKELNJVAZDS-UHFFFAOYSA-N 0.000 description 1
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 1
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 101710103504 CXXC-type zinc finger protein 1 Proteins 0.000 description 1
- 102100036168 CXXC-type zinc finger protein 1 Human genes 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000012848 Dextrorphan Substances 0.000 description 1
- 101150026630 FOXG1 gene Proteins 0.000 description 1
- 102100020871 Forkhead box protein G1 Human genes 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000945692 Homo sapiens Cyclin-dependent kinase-like 5 Proteins 0.000 description 1
- 101001008429 Homo sapiens Nucleobindin-2 Proteins 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 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 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 102100027441 Nucleobindin-2 Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102100028656 Sigma non-opioid intracellular receptor 1 Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- VOXIUXZAOFEFBL-UHFFFAOYSA-N Voacangin Natural products CCC1CC2CN3CC1C(C2)(OC(=O)C)c4[nH]c5ccc(OC)cc5c4C3 VOXIUXZAOFEFBL-UHFFFAOYSA-N 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000004641 brain development Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 238000007418 data mining Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- JAQUASYNZVUNQP-PVAVHDDUSA-N dextrorphan Chemical compound C1C2=CC=C(O)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 JAQUASYNZVUNQP-PVAVHDDUSA-N 0.000 description 1
- 229950006878 dextrorphan Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
- 229950004794 dizocilpine Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000000550 effect on aging Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000006718 epigenetic regulation Effects 0.000 description 1
- INOYCBNLWYEPSB-XHSDSOJGSA-N etoxadrol Chemical compound C([C@H]1[C@H]2CO[C@](O2)(CC)C=2C=CC=CC=2)CCCN1 INOYCBNLWYEPSB-XHSDSOJGSA-N 0.000 description 1
- 229950011255 etoxadrol Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 206010016165 failure to thrive Diseases 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- DKFAAPPUYWQKKF-GOEBONIOSA-N gacyclidine Chemical compound C[C@H]1CCCC[C@@]1(C=1SC=CC=1)N1CCCCC1 DKFAAPPUYWQKKF-GOEBONIOSA-N 0.000 description 1
- 229950003638 gacyclidine Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 230000009599 head growth Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- HSIBGVUMFOSJPD-CFDPKNGZSA-N ibogaine Chemical compound N1([C@@H]2[C@H]3C[C@H](C1)C[C@@H]2CC)CCC1=C3NC2=CC=C(OC)C=C12 HSIBGVUMFOSJPD-CFDPKNGZSA-N 0.000 description 1
- OLOCMRXSJQJJPL-UHFFFAOYSA-N ibogaine Natural products CCC1CC2CC3C1N(C2)C=Cc4c3[nH]c5ccc(OC)cc45 OLOCMRXSJQJJPL-UHFFFAOYSA-N 0.000 description 1
- AREITJMUSRHSBK-UHFFFAOYSA-N ibogamine Natural products CCC1CC2C3CC1CN2CCc4c3[nH]c5ccccc45 AREITJMUSRHSBK-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 229960002623 lacosamide Drugs 0.000 description 1
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- FWUQWDCOOWEXRY-ZDUSSCGKSA-N lanicemine Chemical compound C([C@H](N)C=1C=CC=CC=1)C1=CC=CC=N1 FWUQWDCOOWEXRY-ZDUSSCGKSA-N 0.000 description 1
- 230000013016 learning Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- LPKTWLVEGBNOOX-UHFFFAOYSA-N methoxetamine Chemical compound C=1C=CC(OC)=CC=1C1(NCC)CCCCC1=O LPKTWLVEGBNOOX-UHFFFAOYSA-N 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- OGZQTTHDGQBLBT-UHFFFAOYSA-N neramexane Chemical compound CC1(C)CC(C)(C)CC(C)(N)C1 OGZQTTHDGQBLBT-UHFFFAOYSA-N 0.000 description 1
- 229950004543 neramexane Drugs 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 206010039722 scoliosis Diseases 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 108010085082 sigma receptors Proteins 0.000 description 1
- 108010080097 sigma-1 receptor Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- OLGOYYOHTNZCEO-GBESFXJTSA-N wms-2539 Chemical compound C1[C@@H](F)CCN[C@@H]1[C@@H]1OC(C=2C=CC=CC=2)(C=2C=CC=CC=2)OC1 OLGOYYOHTNZCEO-GBESFXJTSA-N 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、神経発達障害に対する処置方法におけるテトラヒドロ−N,N−ジメチル−2,2−ジフェニル−3−フランメタンアミン塩酸塩(ANAVEX(商標)2−73、AV2−73、またはA2−73)に関する。特に、自閉症スペクトラム障害、脳性麻痺、レット症候群、アンジェルマン症候群、ウィリアムズ症候群、特定不能の広汎性発達障害(PDD−NOS)、小児期崩壊性障害、およびスミス−マゲニス症候群の処置について言及する。さらに、多発性硬化症療法について言及する。
神経発達障害は通常、早期の脳発達における変化を伴う障害に類別される。これらは、典型的にはそれら自身が感覚系および運動系、発話、ならびに言語における行動および認知の変容として現れる。特に、自閉症スペクトラム障害、脳性麻痺、レット症候群、アンジェルマン症候群、ウィリアムズ症候群、およびスミス−マゲニス症候群について言及する。
1.「Rett Syndrome Fact Sheet. NIH Publication No. 09-4863」、National Institute of Neurological Disorders and Stroke (NINDS)、2009年11月
2.Guyら、(2007年)、「Reversal of Neurological Defects in a Mouse Model of Rett Syndrome」、Science、315巻(5815号):1143〜7頁、doi:10.1126/science.1138389. PMID 17289941
3.Trappeら、「MECP2 Mutations in Sporadic Cases of Rett Syndrome Are Almost Exclusively of Paternal Origin」、The American Journal of Human Genetics、68巻(5号):1093〜101頁
4.Fitzgeraldら(1990年)「Rett syndrome and associated movement disorders」、Movement Disorders、5巻(3号):195〜202頁
5.Ricceriら、(2008年)、「Mouse models of Rett syndrome: From behavioural phenotyping to preclinical evaluation of new therapeutic approaches」、Behavioural Pharmacology 19巻(5〜6号):501〜17頁、doi:10.1097/FBP.0b013e32830c3645. PMID 18690105.
6.Lombardiら、「MECP2 disorders: from the clinic to mice and back」、J Clin Invest.、2015年8月3日;125巻(8号):2914〜23頁、doi: 10.1172/JCI78167. Epub2015年8月3日、総説
7.Pohodichら、「Rett syndrome: disruption of epigenetic control of postnatal neurological functions」、Hum Mol Genet.、2015年10月15日;24巻(R1号):Epub2015年6月9日
8.Lotanら、Rett Syndrome: Therapeutic Interventions (Disability Studies)、第1版(Nova Science Publishers, Inc、2011年)、PMID: 26060191
9.Vamvakides、米国特許第9,180,106号、「Sigma receptors ligands with anti-apoptotic and/or pro-apoptotic properties, over cellular mechanisms, exhibiting prototypical cytoprotective and also anti-cancer activity」
10.Mallonら、「EuroPhenome and EMPReSS: online mouse phenotyping resource」、Nucleic Acids Res.、2008年1月;36巻(データベース号):D715〜8頁、Epub2007年9月28日
11.Morganら、「EuroPhenome: a repository for high-throughput mouse phenotyping data」、Nucleic Acids Res.、2010年1月;38巻(データベース号):D577〜85頁、doi: 10.1093/nar/gkp1007. Epub2009年11月23日
12.Tropeaら、「Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice」、Proceedings of the National Academy of Sciences、106巻(6号):2029〜34頁(2009年)
13.Tanら、「Pharmacological therapies for Angelman syndrome」、Wien Med Wochenschr.、2016年1月12日[Epub、冊子掲載前]
14.Kreigら、米国特許出願公開第2015/0152410号、名称「Compositions And Methods For Modulating Mecp2 Expression」
15.Rouxら、米国特許出願公開第2015/0265554号、「Treatment of MeCP-2 Associated Disorders」
16.Surら、米国特許第7,994,127号、Treatment of Rett Syndrome And Other Disorders
特許請求の範囲に記載された発明は、対象におけるレット症候群などの神経発達障害を、前記対象に治療有効量のA2−73を投与することによって処置する方法に関する。特定の実施形態では、本発明は、治療量のA2−73を含む剤形を含む。A2−73の投与量は約0.5〜約500mgであることが記載されている。本発明は、自閉症スペクトラム障害、脳性麻痺、レット症候群、アンジェルマン症候群、ウィリアムズ症候群、およびスミス−マゲニス症候群などの神経発達障害を処置する治療方法をさらに含む。A2−73を使用する多発性硬化症治療もさらに述べられている。
本明細書で使用されるように、「治療有効量」の薬剤または薬剤の組合せは、所望の治療または薬理効果を実現するために十分な量である。特に、メチル化CpG結合タンパク質2(MeCP2)をコードする遺伝子の機能喪失型突然変異を伴う生化学的および機能的異常を改善することができる量について言及する。治療有効量の薬剤または組合せ療法は、対象の病状、年齢、および体重、ならびに薬剤が対象において所望の応答を誘発する能力などの要因に応じて変動し得ると理解されるべきである。投与計画は、最適な治療応答を実現するように調整することができる。治療有効量は、活性化合物のいかなる毒性または有害効果も治療上有益な効果が上回る量でもある。
約8週齢および約12週齢でのMecp2雌の試験
20 WT−ビヒクル(0.25%MC/dH2O)
20 HET−ビヒクル(0.25%MC/dH2O)
20 HET−A2−733(10mg/kg)
20 HET−A2−733(30mg/kg)
体重
ビヒクル処置野生型マウスと変異対照マウスとの間で体重における差は観察されなかった。図1。有意な処置×年齢効果(p<0.001)があり、投与を始めてから6.5週間後、A2−733(30mg/kg)で処置したマウスはビヒクル処置変異マウスより軽量であった。
ロータロッド能力試験は、通常齧歯動物による強制運動活動が加えられた回転するロッドに基づく能力試験である。この試験によって、乗っている時間(秒)または持久力などのパラメータが測定される。試験の機能の一部は、特に実験的薬物の効果を試験する際にまたは外傷性脳傷害後に、対象のバランス、握力、および運動協調性の評価を含む。
ビヒクル処置変異マウスは、ビヒクル処置WTマウスと比較して速やかにかつ低速で落下した。有意な処置効果はいずれの測定についても観察されなかった。
ビヒクル処置変異マウスは、ビヒクル処置WTマウスと比較して速やかにかつ低速で落下した。A2−733処置マウスは両用量とも、ビヒクル処置変異マウスと比較してロッドから落下するまでの時間が長く、高速で落下した。外れ値なしに、高用量の落下測定における速度に対する効果は消失した。変異マウスは、8週齢と12週齢のどちらにおいても、野生型対照と比較して遅く、急速に落下した。
前肢を表面に残したまま、尾部をもって、マウスを穏やかに持ち上げる。後脚の屈曲が指摘される(正常は、後脚が伸びた状態になる)。
ビヒクル処置変異マウスは、ビヒクル処置野生型マウスより屈曲した。A2−733(30mg/kg)で処置したマウスは、ビヒクル処置変異マウスより屈曲しなかった。
聴覚驚愕によって、外部からの音刺激に対する無条件反射応答を測定する。マウスを、5分間の白色雑音(70dB)慣れセッションのためにプレパルス阻害(PPI)チャンバーに入れる。次いで、セッションは、驚愕刺激単独の6つの提示の慣れブロックで始まり、各ブロック内にランダムに提示される異なる6種の試行[なし(刺激なし)、驚愕(120dB)、驚愕+プレパルス(暗騒音を超える4、8および12dB、すなわち74、78または82dB)およびプレパルス単独(82dB)]のPPIブロック10個が続く。正常な驚愕の阻害量が決定され、第1の慣れブロックの驚愕応答を除いて、(驚愕単独の試行から)基本的な驚愕応答の百分率として表される。
ビヒクル処置変異マウスは、ビヒクル処置WTマウスと比較して驚愕しなかったが、PPI応答では差を示さなかった。A2−733(30mg/kg)処置マウスは、ビヒクル処置変異マウスと比較して増加した驚愕応答を示した。処置による差は、PPIでは観察されなかった。
ビヒクル処置変異マウスは、ビヒクル処置WTマウスと比較して驚愕しなかったが、PPI応答では差を示さなかった。驚愕応答において処置効果の傾向があった(p<0.08)。外れ値を除去すると、この傾向は有意になり、A2−733(30mg/kg)マウスが、ビヒクル処置変異マウスと比較して増加した驚愕を示した(p<0.01)。PPI処置相互作用(p<0.05)は、有意ないかなる事後の差も明らかにしなかった。
8週齢におけるニューロキューブによる歩調分析を表1(下記)に提示する。
呼吸変動性の低減
レット症候群の状態を呈する6歳の女児に、A2−73を4mg、毎日、10日間経口投与する。症状について、女児の呼吸は異常である。女児の1分当たりの平均呼吸数を算出して、呼吸変動性を評価する。A2−73投与10日後に、Δ(呼吸数/分)は有意に低減した(変動性の低下を暗示する)。
(実施例2)
心臓の脈拍数
(実施例3)
てんかん発作の低減
(実施例4)
摂食および息詰まり
(実施例5)
アンジェルマン−睡眠およびてんかん発作
(実施例6)
ウィリアムズ症候群−体重増加
(実施例7)
スミス−マゲニス症候群−睡眠
(実施例8)
多発性硬化症
(実施例9)
多発性硬化症
Claims (8)
- 対象における神経発達性の自閉症スペクトラム障害を処置する方法であって、前記対象に、A2−73、ANAVEX1−41、Anavex19−144またはそれらの組合せからなる群から選択される治療剤の治療有効量を投与することによる、方法。
- 前記神経発達性の自閉症スペクトラム障害がレット症候群である、請求項1に記載の方法。
- 前記治療剤がA2−73である、請求項1に記載の方法。
- 前記治療有効量のA2−73が、約0.5mg/日〜約100mg/日の投与量である、請求項3に記載の方法。
- 前記投与量が約1〜約60mg/日である、請求項3または4に記載の方法。
- 前記投与量が約20〜約50mg/日である、請求項3から5に記載の方法。
- 前記投与量が少なくとも約10日間毎日投与される、請求項1から6に記載の方法。
- 前記神経発達性の自閉症スペクトラム障害が、脳性麻痺、アンジェルマン症候群、ウィリアムズ症候群、特定不能の広汎性発達障害(PDD−NOS)、小児期崩壊性障害、スミス−マゲニス症候群または多発性硬化症からなる群から選択される、請求項1に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662287062P | 2016-01-26 | 2016-01-26 | |
US62/287,062 | 2016-01-26 | ||
PCT/US2017/014702 WO2017132127A1 (en) | 2016-01-26 | 2017-01-24 | Neurodevelopmental disorder therapy |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021010835A Division JP7153950B2 (ja) | 2016-01-26 | 2021-01-27 | 神経発達障害療法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2019502716A true JP2019502716A (ja) | 2019-01-31 |
JP2019502716A5 JP2019502716A5 (ja) | 2020-03-05 |
JP6866379B2 JP6866379B2 (ja) | 2021-04-28 |
Family
ID=57966177
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018536130A Active JP6866379B2 (ja) | 2016-01-26 | 2017-01-24 | 神経発達障害療法 |
JP2021010835A Active JP7153950B2 (ja) | 2016-01-26 | 2021-01-27 | 神経発達障害療法 |
JP2022153402A Pending JP2022173373A (ja) | 2016-01-26 | 2022-09-27 | 神経発達障害療法 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021010835A Active JP7153950B2 (ja) | 2016-01-26 | 2021-01-27 | 神経発達障害療法 |
JP2022153402A Pending JP2022173373A (ja) | 2016-01-26 | 2022-09-27 | 神経発達障害療法 |
Country Status (5)
Country | Link |
---|---|
US (5) | US10507196B2 (ja) |
EP (2) | EP4104831A1 (ja) |
JP (3) | JP6866379B2 (ja) |
CA (1) | CA3012199C (ja) |
WO (1) | WO2017132127A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10507196B2 (en) | 2016-01-26 | 2019-12-17 | Anavex Life Sciences Corp. | Neurodevelopmental disorder therapy |
CA3032299C (en) | 2016-07-27 | 2024-03-05 | Anavex Life Sciences Corp. | A2-73 as a therapeutic for insomnia, anxiety and agitation |
CN112105349A (zh) * | 2018-04-12 | 2020-12-18 | 阿纳韦克斯生命科学公司 | A2-73结晶多晶型物质组合物及其使用方法 |
JP2021524741A (ja) | 2018-05-18 | 2021-09-16 | アナベックス ライフ サイエンス コーポレイション | レスポンダ選択および治療の最適化されたsigma−1アゴニスト方法 |
EP3990114A4 (en) * | 2019-06-26 | 2023-08-02 | The Regents of the University of California | METHODS AND COMPOSITIONS FOR THE TREATMENT OF SMITH-MAGENIS SYNDROME |
US20220249427A1 (en) * | 2019-07-22 | 2022-08-11 | Anavex Life Sciences Corp. | Anavex2-73 for the treatment of genetic neurodevelopmental disorders |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100069484A1 (en) * | 2007-01-17 | 2010-03-18 | Alexandre Vamvakides | SIGMA(s)-RECEPTOR LIGANDS WITH ANTI-APOPTOTIC AND/OR PRO-APOPTOTIC PROPERTIES OVER CELLULAR BIOCHEMICAL MECHANISMS, WITH NEUROPROTECTIVE, ANTI-CANCER, ANTI-METASTATIC AND ANTI-(CHRONIC) INFLAMMATORY ACTION |
US20150359759A1 (en) * | 2013-01-25 | 2015-12-17 | Case Western Reserve University | Compositions and methods for the treatment of pervasive development disorders |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GR1002616B (el) * | 1996-02-21 | 1997-02-20 | Συνθεση και μεθοδος συνθεσης μοριου: τετραυδρο-ν,ν-διμεθυλο-2,2-διφαινυλο-3-φουρανομεθαναμινης (αε 37), αντισπασμωδικης, αντικαταθλιπτικης και νοοτροπικης δρασης. | |
GR1004208B (en) * | 2001-10-15 | 2003-04-04 | Αλεξανδρος Βαμβακιδης | Aminotetrahydrofuran derivatives, muscarinic/sigma/sodium channel ligands, with synergic sigma/muscarinic (neuroactivating) and sigma/sodium channel (neuroprotective) components, as prototypical activating - neuroprotectors and neuroregenerative drugs |
FR2897535B1 (fr) | 2006-02-21 | 2012-07-20 | Alexandre Vamvakides | Les sigma ligands : (mono- ou di-alkylaminoalkyl)-y- butyrolactones, leurs analogues aminotetrodrafuranes et les (1-adamantyl) benzene(s) alkylamines en tant que modulateurs prototypiques des recepteurs cellulaires |
AU2008262387A1 (en) | 2007-06-08 | 2008-12-18 | Massachusetts Institute Of Technology | IGF for the treatment of Rett Syndrome and synaptic disorders |
GR1006794B (el) | 2009-02-26 | 2010-06-04 | Αλεξανδρος Βαμβακιδης | Προσδετες των σιγμα υποδοχεων, αντι-αποπτωτικες και προ-αποπτωτικες ιδιοτητες επι των κυτταρικων μηχανισμων, και με πρωτοτυπη κυτταρο-προστατευτικη αλλα και αντικαρκινικη δραση |
WO2012055826A1 (en) | 2010-10-25 | 2012-05-03 | Universite De La Mediterranee (Aix-Marseille Ii) | TREATMENT OF MeCP2-ASSOCIATED DISORDERS |
EA201492116A1 (ru) | 2012-05-16 | 2015-05-29 | Рана Терапьютикс, Инк. | Композиции и способы для модулирования экспрессии mecp2 |
US10507196B2 (en) * | 2016-01-26 | 2019-12-17 | Anavex Life Sciences Corp. | Neurodevelopmental disorder therapy |
-
2017
- 2017-01-24 US US16/068,703 patent/US10507196B2/en active Active
- 2017-01-24 CA CA3012199A patent/CA3012199C/en active Active
- 2017-01-24 EP EP22189051.0A patent/EP4104831A1/en active Pending
- 2017-01-24 WO PCT/US2017/014702 patent/WO2017132127A1/en active Application Filing
- 2017-01-24 EP EP17703579.7A patent/EP3407880B1/en active Active
- 2017-01-24 JP JP2018536130A patent/JP6866379B2/ja active Active
-
2019
- 2019-12-17 US US16/717,921 patent/US10888543B2/en active Active
-
2021
- 2021-01-08 US US17/145,073 patent/US11446275B2/en active Active
- 2021-01-27 JP JP2021010835A patent/JP7153950B2/ja active Active
-
2022
- 2022-08-17 US US17/890,083 patent/US11839600B2/en active Active
- 2022-09-27 JP JP2022153402A patent/JP2022173373A/ja active Pending
-
2023
- 2023-10-30 US US18/497,850 patent/US20240066003A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100069484A1 (en) * | 2007-01-17 | 2010-03-18 | Alexandre Vamvakides | SIGMA(s)-RECEPTOR LIGANDS WITH ANTI-APOPTOTIC AND/OR PRO-APOPTOTIC PROPERTIES OVER CELLULAR BIOCHEMICAL MECHANISMS, WITH NEUROPROTECTIVE, ANTI-CANCER, ANTI-METASTATIC AND ANTI-(CHRONIC) INFLAMMATORY ACTION |
US20150359759A1 (en) * | 2013-01-25 | 2015-12-17 | Case Western Reserve University | Compositions and methods for the treatment of pervasive development disorders |
Also Published As
Publication number | Publication date |
---|---|
JP2021063136A (ja) | 2021-04-22 |
US20200246303A1 (en) | 2020-08-06 |
EP4104831A1 (en) | 2022-12-21 |
CA3012199A1 (en) | 2017-08-03 |
US20190022052A1 (en) | 2019-01-24 |
CA3012199C (en) | 2024-05-07 |
US10507196B2 (en) | 2019-12-17 |
EP3407880B1 (en) | 2022-08-17 |
EP3407880A1 (en) | 2018-12-05 |
JP2022173373A (ja) | 2022-11-18 |
US20210228532A1 (en) | 2021-07-29 |
JP6866379B2 (ja) | 2021-04-28 |
US11446275B2 (en) | 2022-09-20 |
US11839600B2 (en) | 2023-12-12 |
US20240066003A1 (en) | 2024-02-29 |
US20220387373A1 (en) | 2022-12-08 |
US10888543B2 (en) | 2021-01-12 |
WO2017132127A1 (en) | 2017-08-03 |
JP7153950B2 (ja) | 2022-10-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6866379B2 (ja) | 神経発達障害療法 | |
JP5875191B2 (ja) | Cmt及び関連障害を処置するための新たな組成物 | |
JP5923459B2 (ja) | 女性性的機能不全の治療における薬学的製剤およびその使用方法 | |
US20120225949A1 (en) | Compositions and methods for treating bipolar disorder | |
US20200323823A1 (en) | Methods for the treatment of depression | |
JP2008513491A (ja) | 自閉症、強迫神経症、および衝動性の治療のためのメマンチン(ナメンダ)の使用 | |
WO2011107583A1 (en) | Substituted 4-phenyl-n-alkyl-piperidines for preventing onset or slowing progression of neurodegenerative disorders | |
EP3970706A1 (en) | Use of cannabidiolic acid in the treatment of cognitive disorders | |
McDOUGLE et al. | Risperidone in adults with autism or pervasive developmental disorder | |
JP2010534628A (ja) | 神経変性障害を治療するためのネラメキサンの新規組合せ | |
CN114901270A (zh) | 治疗自闭症谱系障碍的症状的方法 | |
JP2011121976A (ja) | 線維筋痛症に伴う口腔乾燥症を改善するための線維筋痛症に伴う口腔乾燥症改善用医薬組成物 | |
US20170007596A1 (en) | Treatment of multiple sclerosis with combination of laquinimod and flupirtine | |
TW202308653A (zh) | 以神經活性類固醇進行治療的方法 | |
US20190151294A1 (en) | Treatment of alcoholism and depression and/or dysphoric mood using ibudilast | |
Hill et al. | Prevalence of sleep apnoea, sleepiness and behavioural/emotional disturbances in adults with Down's syndrome in Scotland |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200121 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200121 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20201124 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210127 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210309 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210407 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6866379 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |