DK3137093T3 - TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE (AD) - Google Patents
TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE (AD) Download PDFInfo
- Publication number
- DK3137093T3 DK3137093T3 DK15720059.3T DK15720059T DK3137093T3 DK 3137093 T3 DK3137093 T3 DK 3137093T3 DK 15720059 T DK15720059 T DK 15720059T DK 3137093 T3 DK3137093 T3 DK 3137093T3
- Authority
- DK
- Denmark
- Prior art keywords
- hydroxide
- patient
- administered
- use according
- aluminum
- Prior art date
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims description 152
- 238000011282 treatment Methods 0.000 title claims description 41
- 230000002265 prevention Effects 0.000 title claims description 8
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 30
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 6
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 239000008139 complexing agent Substances 0.000 claims description 4
- 239000003599 detergent Substances 0.000 claims description 4
- 229960001484 edetic acid Drugs 0.000 claims description 4
- 229910021645 metal ion Inorganic materials 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 239000007983 Tris buffer Substances 0.000 claims description 3
- FAHBNUUHRFUEAI-UHFFFAOYSA-M hydroxidooxidoaluminium Chemical compound O[Al]=O FAHBNUUHRFUEAI-UHFFFAOYSA-M 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- 150000005846 sugar alcohols Chemical class 0.000 claims description 3
- 150000008163 sugars Chemical class 0.000 claims description 3
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 claims description 3
- 229960004906 thiomersal Drugs 0.000 claims description 3
- 229910052593 corundum Inorganic materials 0.000 claims description 2
- 229940071643 prefilled syringe Drugs 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 229910001845 yogo sapphire Inorganic materials 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 11
- VXAUWWUXCIMFIM-UHFFFAOYSA-M aluminum;oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Al+3] VXAUWWUXCIMFIM-UHFFFAOYSA-M 0.000 claims 7
- 229910018404 Al2 O3 Inorganic materials 0.000 claims 1
- -1 aluminium-oxyhydroxide Chemical compound 0.000 description 127
- 229940037003 alum Drugs 0.000 description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 201000010099 disease Diseases 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 22
- 210000004556 brain Anatomy 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 20
- 239000002131 composite material Substances 0.000 description 19
- 229960005486 vaccine Drugs 0.000 description 18
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 16
- 239000004411 aluminium Substances 0.000 description 16
- 229910052782 aluminium Inorganic materials 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 239000000825 pharmaceutical preparation Substances 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- 102000013498 tau Proteins Human genes 0.000 description 15
- 108010026424 tau Proteins Proteins 0.000 description 15
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 238000002595 magnetic resonance imaging Methods 0.000 description 13
- 239000000090 biomarker Substances 0.000 description 12
- 210000001320 hippocampus Anatomy 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 230000000051 modifying effect Effects 0.000 description 11
- 230000008859 change Effects 0.000 description 10
- 230000001149 cognitive effect Effects 0.000 description 10
- 230000007423 decrease Effects 0.000 description 10
- 238000007920 subcutaneous administration Methods 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 208000010877 cognitive disease Diseases 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000002490 cerebral effect Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 208000037259 Amyloid Plaque Diseases 0.000 description 7
- 230000003920 cognitive function Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
- 159000000013 aluminium salts Chemical class 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 208000022120 Jeavons syndrome Diseases 0.000 description 5
- 229910000329 aluminium sulfate Inorganic materials 0.000 description 5
- 230000019771 cognition Effects 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000000971 hippocampal effect Effects 0.000 description 5
- 230000015654 memory Effects 0.000 description 5
- 238000002600 positron emission tomography Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- 206010024769 Local reaction Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000006999 cognitive decline Effects 0.000 description 4
- 230000003750 conditioning effect Effects 0.000 description 4
- 229940031670 conjugate vaccine Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 210000000689 upper leg Anatomy 0.000 description 4
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
- 206010003694 Atrophy Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000029749 Microtubule Human genes 0.000 description 3
- 108091022875 Microtubule Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 3
- 230000003941 amyloidogenesis Effects 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 210000003140 lateral ventricle Anatomy 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000004688 microtubule Anatomy 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 206010033675 panniculitis Diseases 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
- 108010060123 Conjugate Vaccines Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
- 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 2
- 102000000874 Pyrin Domain-Containing 3 Protein NLR Family Human genes 0.000 description 2
- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 2
- 229940001007 aluminium phosphate Drugs 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000006933 amyloid-beta aggregation Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000001353 entorhinal cortex Anatomy 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 230000006951 hyperphosphorylation Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 238000010984 neurological examination Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000001991 pathophysiological effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012301 transgenic model Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- PKXWXXPNHIWQHW-RCBQFDQVSA-N (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide Chemical compound C1CN(C)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](O)C(C)C)C2=CC=CC=C21 PKXWXXPNHIWQHW-RCBQFDQVSA-N 0.000 description 1
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 1
- 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 1
- 229940124596 AChE inhibitor Drugs 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- XEAOPVUAMONVLA-QGZVFWFLSA-N Avagacestat Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)N([C@H](CCC(F)(F)F)C(=O)N)CC(C(=C1)F)=CC=C1C=1N=CON=1 XEAOPVUAMONVLA-QGZVFWFLSA-N 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 206010021034 Hypometabolism Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 235000011126 aluminium potassium sulphate Nutrition 0.000 description 1
- 230000007791 alzheimer disease like pathology Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940027999 antiseptic and disinfectant aluminium agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 229950008567 avagacestat Drugs 0.000 description 1
- 230000008335 axon cargo transport Effects 0.000 description 1
- 229950001863 bapineuzumab Drugs 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 210000001947 dentate gyrus Anatomy 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000001073 episodic memory Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000007496 glass forming Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 101150042363 hemH gene Proteins 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 210000001981 hip bone Anatomy 0.000 description 1
- 230000004694 hippocampus damage Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 230000007388 microgliosis Effects 0.000 description 1
- 102000021160 microtubule binding proteins Human genes 0.000 description 1
- 108091011150 microtubule binding proteins Proteins 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- CAMWVBRDIKKGII-UHFFFAOYSA-M n,n-dimethyl-4-(1-methylpyridin-1-ium-4-yl)aniline;iodide Chemical compound [I-].C1=CC(N(C)C)=CC=C1C1=CC=[N+](C)C=C1 CAMWVBRDIKKGII-UHFFFAOYSA-M 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000003959 neuroinflammation Effects 0.000 description 1
- 230000002314 neuroinflammatory effect Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007121 neuropathological change Effects 0.000 description 1
- 238000010855 neuropsychological testing Methods 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 210000001152 parietal lobe Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 229940050271 potassium alum Drugs 0.000 description 1
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000007101 progressive neurodegeneration Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 229950001900 semagacestat Drugs 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229950007874 solanezumab Drugs 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000003325 tomography Methods 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
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000011240 wet gel Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
-
- 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
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- 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
- A61K9/08—Solutions
-
- 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
Landscapes
- Health & Medical Sciences (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)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14166355 | 2014-04-29 | ||
| EP14166354 | 2014-04-29 | ||
| PCT/EP2015/059339 WO2015165966A1 (en) | 2014-04-29 | 2015-04-29 | Treatment and prevention of alzheimer's disease (ad) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3137093T3 true DK3137093T3 (en) | 2017-12-11 |
Family
ID=53039896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15720059.3T DK3137093T3 (en) | 2014-04-29 | 2015-04-29 | TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE (AD) |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US10478454B2 (enExample) |
| EP (2) | EP3269376B1 (enExample) |
| JP (1) | JP6692755B2 (enExample) |
| KR (1) | KR102388363B1 (enExample) |
| CN (1) | CN106659738B (enExample) |
| AU (1) | AU2015254663B2 (enExample) |
| CA (1) | CA2946928C (enExample) |
| CY (1) | CY1119674T1 (enExample) |
| DK (1) | DK3137093T3 (enExample) |
| ES (2) | ES2824763T3 (enExample) |
| HR (1) | HRP20171896T1 (enExample) |
| HU (1) | HUE037501T2 (enExample) |
| LT (1) | LT3137093T (enExample) |
| NO (1) | NO3137093T3 (enExample) |
| PL (1) | PL3137093T3 (enExample) |
| PT (1) | PT3137093T (enExample) |
| SI (1) | SI3137093T1 (enExample) |
| WO (1) | WO2015165966A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106535924A (zh) | 2014-04-29 | 2017-03-22 | 阿费里斯股份公司 | 阿尔茨海默病(ad)的治疗和预防 |
| KR102506460B1 (ko) * | 2014-04-29 | 2023-03-03 | 어드밴티지 테라퓨틱스, 인코포레이티드 | 알츠하이머병（ａｄ）의 치료 및 예방 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994016327A1 (en) * | 1993-01-14 | 1994-07-21 | Pollard Harvey B | Methods and compositions for blocking amyloid protein ion channels |
| EP1007040B1 (en) * | 1997-08-21 | 2002-05-08 | P.N. Gerolymatos S.A. | Use of phanquinone for the treatment of alzheimer's disease |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| CN104436212A (zh) * | 2010-03-29 | 2015-03-25 | 诺华股份有限公司 | 包含与病毒样颗粒偶联的淀粉样β1-6肽及佐剂的组合物 |
| CN106535924A (zh) * | 2014-04-29 | 2017-03-22 | 阿费里斯股份公司 | 阿尔茨海默病(ad)的治疗和预防 |
| KR102506460B1 (ko) * | 2014-04-29 | 2023-03-03 | 어드밴티지 테라퓨틱스, 인코포레이티드 | 알츠하이머병（ａｄ）의 치료 및 예방 |
-
2015
- 2015-04-29 WO PCT/EP2015/059339 patent/WO2015165966A1/en not_active Ceased
- 2015-04-29 PT PT157200593T patent/PT3137093T/pt unknown
- 2015-04-29 AU AU2015254663A patent/AU2015254663B2/en active Active
- 2015-04-29 DK DK15720059.3T patent/DK3137093T3/en active
- 2015-04-29 HU HUE15720059A patent/HUE037501T2/hu unknown
- 2015-04-29 US US15/307,082 patent/US10478454B2/en active Active
- 2015-04-29 SI SI201530145T patent/SI3137093T1/en unknown
- 2015-04-29 ES ES17189527T patent/ES2824763T3/es active Active
- 2015-04-29 EP EP17189527.9A patent/EP3269376B1/en active Active
- 2015-04-29 LT LTEP15720059.3T patent/LT3137093T/lt unknown
- 2015-04-29 ES ES15720059.3T patent/ES2651537T3/es active Active
- 2015-04-29 CA CA2946928A patent/CA2946928C/en active Active
- 2015-04-29 NO NO15720059A patent/NO3137093T3/no unknown
- 2015-04-29 EP EP15720059.3A patent/EP3137093B1/en active Active
- 2015-04-29 KR KR1020167033332A patent/KR102388363B1/ko active Active
- 2015-04-29 JP JP2016565267A patent/JP6692755B2/ja active Active
- 2015-04-29 CN CN201580029861.5A patent/CN106659738B/zh active Active
- 2015-04-29 HR HRP20171896TT patent/HRP20171896T1/hr unknown
- 2015-04-29 PL PL15720059T patent/PL3137093T3/pl unknown
-
2017
- 2017-12-13 CY CY20171101303T patent/CY1119674T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3269376A1 (en) | 2018-01-17 |
| ES2824763T3 (es) | 2021-05-13 |
| AU2015254663A1 (en) | 2016-11-10 |
| CN106659738B (zh) | 2021-02-09 |
| HRP20171896T1 (hr) | 2018-02-23 |
| PL3137093T3 (pl) | 2018-06-29 |
| CA2946928A1 (en) | 2015-11-05 |
| KR20160145822A (ko) | 2016-12-20 |
| ES2651537T3 (es) | 2018-01-29 |
| KR102388363B1 (ko) | 2022-04-19 |
| AU2015254663B2 (en) | 2020-04-02 |
| CN106659738A (zh) | 2017-05-10 |
| SI3137093T1 (en) | 2018-01-31 |
| PT3137093T (pt) | 2017-12-19 |
| EP3137093B1 (en) | 2017-09-13 |
| HUE037501T2 (hu) | 2018-08-28 |
| EP3137093A1 (en) | 2017-03-08 |
| CY1119674T1 (el) | 2018-04-04 |
| JP2017518275A (ja) | 2017-07-06 |
| JP6692755B2 (ja) | 2020-05-13 |
| CA2946928C (en) | 2023-01-31 |
| LT3137093T (lt) | 2017-12-11 |
| WO2015165966A1 (en) | 2015-11-05 |
| EP3269376B1 (en) | 2020-07-15 |
| NO3137093T3 (enExample) | 2018-02-10 |
| US20170049812A1 (en) | 2017-02-23 |
| US10478454B2 (en) | 2019-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240148782A1 (en) | Treatment and prevention of alzheimer's disease (ad) | |
| US20220062412A1 (en) | Treatment of alzheimer's disease (ad) with an aluminum salt | |
| DK3137093T3 (en) | TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE (AD) | |
| WO2015165971A1 (en) | Treatment and prevention of alzheimer's disease (ad) |