CA3073991A1 - Use of neuropeptide drug for treatment of cadasil - Google Patents
Use of neuropeptide drug for treatment of cadasil Download PDFInfo
- Publication number
- CA3073991A1 CA3073991A1 CA3073991A CA3073991A CA3073991A1 CA 3073991 A1 CA3073991 A1 CA 3073991A1 CA 3073991 A CA3073991 A CA 3073991A CA 3073991 A CA3073991 A CA 3073991A CA 3073991 A1 CA3073991 A1 CA 3073991A1
- Authority
- CA
- Canada
- Prior art keywords
- cerebrolysin
- cadasil
- use according
- treated
- concentrate
- 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
- 208000010482 CADASIL Diseases 0.000 title claims abstract description 79
- 208000033221 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 title claims abstract description 79
- 238000011282 treatment Methods 0.000 title claims description 20
- 208000033935 Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy Diseases 0.000 title claims 10
- 208000016886 cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 title claims 10
- 239000003814 drug Substances 0.000 title description 3
- 108090000189 Neuropeptides Proteins 0.000 title description 2
- 229940079593 drug Drugs 0.000 title description 2
- 102000003797 Neuropeptides Human genes 0.000 title 1
- 239000012141 concentrate Substances 0.000 claims description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 230000035772 mutation Effects 0.000 claims description 10
- 238000001802 infusion Methods 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 101150103623 NOTCH3 gene Proteins 0.000 claims description 4
- 239000012895 dilution Substances 0.000 claims description 3
- 238000010790 dilution Methods 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 201000010099 disease Diseases 0.000 description 12
- 210000004885 white matter Anatomy 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 102000001760 Notch3 Receptor Human genes 0.000 description 10
- 108010029756 Notch3 Receptor Proteins 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 230000001717 pathogenic effect Effects 0.000 description 8
- 201000004810 Vascular dementia Diseases 0.000 description 7
- 210000000877 corpus callosum Anatomy 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000006907 apoptotic process Effects 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 208000019695 Migraine disease Diseases 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 206010027599 migraine 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 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 210000003668 pericyte Anatomy 0.000 description 4
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000002739 subcortical effect Effects 0.000 description 4
- 210000003934 vacuole Anatomy 0.000 description 4
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 206010072731 White matter lesion Diseases 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127218 antiplatelet drug Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229960002989 glutamic acid Drugs 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002537 thrombolytic effect Effects 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 229960004799 tryptophan Drugs 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000027647 Cerebral Cortical Thinning Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 208000004552 Lacunar Stroke Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 239000006035 Tryptophane Substances 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000009598 prenatal testing Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 102200063959 rs367543285 Human genes 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000003478 temporal lobe Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000010981 turquoise Substances 0.000 description 2
- 230000002477 vacuolizing effect Effects 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000004429 Calibre Substances 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000577202 Homo sapiens Neurogenic locus notch homolog protein 3 Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000002867 adherens junction Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000003140 astrocytic effect Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 230000006736 behavioral deficit Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 208000011142 cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Diseases 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000003788 cerebral perfusion Effects 0.000 description 1
- 230000010456 cerebrovascular autoregulation Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 230000007577 cortical microinfarct Effects 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 238000002598 diffusion tensor imaging Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 208000022059 functional hyperemia Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000011686 genetic mapping animal model Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 238000013427 histology analysis Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 201000011489 infantile myofibromatosis Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000002482 lateral meningocele syndrome Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010060 microvascular dysfunction Effects 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000008529 pathological progression Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229940084026 sodium valproate Drugs 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 230000037436 splice-site mutation Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000009861 stroke prevention Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000010246 ultrastructural analysis Methods 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
-
- 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
- A61P25/28—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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/48—Nerve growth factor [NGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Ophthalmology & Optometry (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Marine Sciences & Fisheries (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17188180.8A EP3449931B1 (en) | 2017-08-28 | 2017-08-28 | Use of cerebrolysin |
| EP17188180.8 | 2017-08-28 | ||
| PCT/EP2018/073106 WO2019042983A1 (en) | 2017-08-28 | 2018-08-28 | USE OF CERBROLYSINE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3073991A1 true CA3073991A1 (en) | 2019-03-07 |
Family
ID=59745228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3073991A Pending CA3073991A1 (en) | 2017-08-28 | 2018-08-28 | Use of neuropeptide drug for treatment of cadasil |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20200376040A1 (enExample) |
| EP (2) | EP3449931B1 (enExample) |
| JP (1) | JP7281450B2 (enExample) |
| KR (1) | KR102676274B1 (enExample) |
| CN (1) | CN111050780B (enExample) |
| AU (1) | AU2018326339A1 (enExample) |
| CA (1) | CA3073991A1 (enExample) |
| EA (1) | EA202090108A1 (enExample) |
| ES (2) | ES2767070T3 (enExample) |
| HR (1) | HRP20200031T1 (enExample) |
| MX (1) | MX2020002267A (enExample) |
| PH (1) | PH12020500376A1 (enExample) |
| PL (2) | PL3449931T3 (enExample) |
| UA (1) | UA129400C2 (enExample) |
| WO (1) | WO2019042983A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220168325A1 (en) * | 2019-03-25 | 2022-06-02 | The University Of Vermont | Methods to promote cerebral blood flow in the brain |
| ES2964145T3 (es) | 2020-07-13 | 2024-04-04 | Ever Neuro Pharma Gmbh | Método para producir un hidrolizado de proteína de cerebro de mamífero |
| EP4347634A1 (en) * | 2021-06-02 | 2024-04-10 | Regeneron Pharmaceuticals, Inc. | Treatment of cerebrovascular disease with neurogenic locus notch homolog protein 3 (notch3) agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69126563T2 (de) | 1990-04-12 | 1998-02-05 | Ebewe Arzneimittel | Verwendung einer Mischung von Peptiden and Aminosäuren für die Prophylaxis oder Behandlung von Dementia |
| JP2012501967A (ja) | 2008-08-20 | 2012-01-26 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 調節放出型多粒子のホットメルト押出成形 |
-
2017
- 2017-08-28 ES ES17188180T patent/ES2767070T3/es active Active
- 2017-08-28 EP EP17188180.8A patent/EP3449931B1/en active Active
- 2017-08-28 PL PL17188180T patent/PL3449931T3/pl unknown
-
2018
- 2018-08-28 AU AU2018326339A patent/AU2018326339A1/en not_active Abandoned
- 2018-08-28 UA UAA202001881A patent/UA129400C2/uk unknown
- 2018-08-28 WO PCT/EP2018/073106 patent/WO2019042983A1/en not_active Ceased
- 2018-08-28 CN CN201880055542.5A patent/CN111050780B/zh active Active
- 2018-08-28 EP EP18759322.3A patent/EP3675879B1/en active Active
- 2018-08-28 MX MX2020002267A patent/MX2020002267A/es unknown
- 2018-08-28 PL PL18759322T patent/PL3675879T3/pl unknown
- 2018-08-28 ES ES18759322T patent/ES2901508T3/es active Active
- 2018-08-28 CA CA3073991A patent/CA3073991A1/en active Pending
- 2018-08-28 EA EA202090108A patent/EA202090108A1/ru unknown
- 2018-08-28 JP JP2020512835A patent/JP7281450B2/ja active Active
- 2018-08-28 US US16/642,307 patent/US20200376040A1/en active Pending
- 2018-08-28 KR KR1020207007069A patent/KR102676274B1/ko active Active
-
2020
- 2020-01-09 HR HRP20200031TT patent/HRP20200031T1/hr unknown
- 2020-02-26 PH PH12020500376A patent/PH12020500376A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN111050780A (zh) | 2020-04-21 |
| AU2018326339A1 (en) | 2020-03-05 |
| KR20200045503A (ko) | 2020-05-04 |
| PH12020500376A1 (en) | 2020-12-07 |
| JP2020531568A (ja) | 2020-11-05 |
| HRP20200031T1 (hr) | 2020-03-20 |
| US20200376040A1 (en) | 2020-12-03 |
| PL3449931T3 (pl) | 2020-06-01 |
| CN111050780B (zh) | 2023-11-03 |
| KR102676274B1 (ko) | 2024-06-18 |
| EA202090108A1 (ru) | 2020-03-31 |
| EP3449931A1 (en) | 2019-03-06 |
| UA129400C2 (uk) | 2025-04-16 |
| ES2767070T3 (es) | 2020-06-16 |
| WO2019042983A1 (en) | 2019-03-07 |
| JP7281450B2 (ja) | 2023-05-25 |
| ES2901508T3 (es) | 2022-03-22 |
| EP3675879A1 (en) | 2020-07-08 |
| EP3675879B1 (en) | 2021-09-15 |
| EP3449931B1 (en) | 2019-10-16 |
| MX2020002267A (es) | 2020-10-22 |
| PL3675879T3 (pl) | 2022-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jana et al. | Fibrillar amyloid-β peptides activate microglia via TLR2: implications for Alzheimer’s disease | |
| RU2733464C2 (ru) | Препараты tpp1 и способы лечения заболевания cln2 | |
| EP3675879B1 (en) | Cerebrolysin for use in the treatment of cadasil | |
| BR112020010916A2 (pt) | moduladores da atividade do complemento | |
| Broussalis et al. | Current therapies in ischemic stroke. Part B. Future candidates in stroke therapy and experimental studies | |
| Gentile et al. | Cluster headache attacks and multiple sclerosis | |
| Khan et al. | Fingolimod-associated macular edema in the treatment of multiple sclerosis | |
| Dhapola et al. | Exploring Retinal Neurodegeneration in Alzheimer’s Disease: A Molecular and Cellular Perspective | |
| HK40026040B (en) | Cerebrolysin for use in the treatment of cadasil | |
| US20210330757A1 (en) | Methods and compositions for inducing neural plasticity | |
| EA040978B1 (ru) | Применение церебролизина | |
| HRP20220370A1 (hr) | Postupci liječenja cln2 bolesti kod pedijatrijskih subjekata | |
| WO2022061812A1 (zh) | 醋酸格拉替雷在制备Aβ42毒性抑制剂和清除剂中的应用 | |
| Wang et al. | Age-and Sex-Specific Regulation of Serine Racemase in the Retina of an Alzheimer's Disease Mouse | |
| Ramos Pérez et al. | Inflammation in the anterior visual pathway in multiple sclerosis: what do the animal models teach us? | |
| Kogo et al. | Transient Retinal Vessel Whitening After Whole-Ventricle Radiotherapy | |
| Corey-Bloom et al. | O1-05-01 The safety and efficacy of an extended-release formulation of galantamine (reminyl ER) in the treatment of Alzheimer's disease | |
| Cordano et al. | USA. 4Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa 16132, Italy. 5IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy. 6Department of Neurology, S. Paolo Hospital, Savona 17100, Italy. | |
| BR122025005065A2 (pt) | Formulações e composições de tpp1, bem como uso no tratamento de doença lcn2 | |
| BR112017023805B1 (pt) | Formulações e composições de tpp1, bem como uso no tratamento de doença lcn2 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220916 |
|
| EEER | Examination request |
Effective date: 20220916 |
|
| EEER | Examination request |
Effective date: 20220916 |
|
| EEER | Examination request |
Effective date: 20220916 |
|
| EEER | Examination request |
Effective date: 20220916 |
|
| EEER | Examination request |
Effective date: 20220916 |