JP6320931B2 - リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ - Google Patents
リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ Download PDFInfo
- Publication number
- JP6320931B2 JP6320931B2 JP2014547767A JP2014547767A JP6320931B2 JP 6320931 B2 JP6320931 B2 JP 6320931B2 JP 2014547767 A JP2014547767 A JP 2014547767A JP 2014547767 A JP2014547767 A JP 2014547767A JP 6320931 B2 JP6320931 B2 JP 6320931B2
- Authority
- JP
- Japan
- Prior art keywords
- disease
- component
- activity
- ambroxol
- combination
- 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.)
- Expired - Fee Related
Links
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 title claims description 345
- 229960005174 ambroxol Drugs 0.000 title claims description 280
- 150000001875 compounds Chemical class 0.000 title description 224
- 102000004190 Enzymes Human genes 0.000 title description 83
- 108090000790 Enzymes Proteins 0.000 title description 83
- 230000002132 lysosomal effect Effects 0.000 title description 32
- 230000000694 effects Effects 0.000 claims description 434
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 340
- 201000010099 disease Diseases 0.000 claims description 328
- 230000002829 reductive effect Effects 0.000 claims description 261
- 150000003839 salts Chemical class 0.000 claims description 227
- 238000011282 treatment Methods 0.000 claims description 178
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 176
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims description 110
- 108010030291 alpha-Galactosidase Proteins 0.000 claims description 108
- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 claims description 108
- 229960003870 bromhexine Drugs 0.000 claims description 103
- 208000024720 Fabry Disease Diseases 0.000 claims description 97
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims description 80
- 201000004502 glycogen storage disease II Diseases 0.000 claims description 80
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims description 78
- 102000005840 alpha-Galactosidase Human genes 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 55
- 239000002552 dosage form Substances 0.000 claims description 43
- 230000002265 prevention Effects 0.000 claims description 34
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 33
- UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical group CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 24
- 230000001965 increasing effect Effects 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 108010045758 lysosomal proteins Proteins 0.000 description 476
- 108010006519 Molecular Chaperones Proteins 0.000 description 114
- 208000015439 Lysosomal storage disease Diseases 0.000 description 111
- 108090000623 proteins and genes Proteins 0.000 description 100
- 230000035772 mutation Effects 0.000 description 90
- 102000004169 proteins and genes Human genes 0.000 description 89
- 235000018102 proteins Nutrition 0.000 description 88
- 208000018737 Parkinson disease Diseases 0.000 description 85
- 229940088598 enzyme Drugs 0.000 description 78
- 230000000144 pharmacologic effect Effects 0.000 description 78
- LXBIFEVIBLOUGU-DPYQTVNSSA-N migalastat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@H]1O LXBIFEVIBLOUGU-DPYQTVNSSA-N 0.000 description 75
- 229950007469 migalastat Drugs 0.000 description 75
- 208000008955 Mucolipidoses Diseases 0.000 description 73
- 201000008892 GM1 Gangliosidosis Diseases 0.000 description 70
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 65
- 201000008049 fucosidosis Diseases 0.000 description 57
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 description 57
- 206010056893 Mucopolysaccharidosis VII Diseases 0.000 description 54
- 208000021811 Sandhoff disease Diseases 0.000 description 54
- 208000022292 Tay-Sachs disease Diseases 0.000 description 54
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 53
- 208000028226 Krabbe disease Diseases 0.000 description 53
- 206010072927 Mucolipidosis type I Diseases 0.000 description 53
- 201000008977 glycoproteinosis Diseases 0.000 description 51
- 208000011985 sialidosis Diseases 0.000 description 51
- 201000008333 alpha-mannosidosis Diseases 0.000 description 49
- 230000007547 defect Effects 0.000 description 49
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 47
- 102100026277 Alpha-galactosidase A Human genes 0.000 description 46
- 230000006806 disease prevention Effects 0.000 description 46
- 201000006486 beta-mannosidosis Diseases 0.000 description 44
- LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 description 43
- 102000005431 Molecular Chaperones Human genes 0.000 description 43
- 108700001567 Type I Schindler Disease Proteins 0.000 description 43
- LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 description 42
- 208000025923 Mucopolysaccharidosis type 4B Diseases 0.000 description 41
- 208000012091 mucopolysaccharidosis type IVB Diseases 0.000 description 41
- 230000015556 catabolic process Effects 0.000 description 39
- 238000006731 degradation reaction Methods 0.000 description 39
- 239000002253 acid Substances 0.000 description 32
- 208000024891 symptom Diseases 0.000 description 27
- 125000003118 aryl group Chemical group 0.000 description 26
- 208000011580 syndromic disease Diseases 0.000 description 26
- 235000000346 sugar Nutrition 0.000 description 25
- 230000032258 transport Effects 0.000 description 25
- 108010017544 Glucosylceramidase Proteins 0.000 description 24
- 102000004547 Glucosylceramidase Human genes 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 23
- 125000000217 alkyl group Chemical group 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 21
- 230000007812 deficiency Effects 0.000 description 20
- 101710124976 Beta-hexosaminidase A Proteins 0.000 description 18
- 230000006870 function Effects 0.000 description 18
- 102000035160 transmembrane proteins Human genes 0.000 description 17
- 108091005703 transmembrane proteins Proteins 0.000 description 17
- DRHXTSWSUAJOJZ-FMDGEEDCSA-N (3ar,5r,6s,7r,7ar)-5-(hydroxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical group S1C(C)=N[C@H]2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]2O DRHXTSWSUAJOJZ-FMDGEEDCSA-N 0.000 description 16
- 101710124978 Beta-hexosaminidase B Proteins 0.000 description 16
- 229930182830 galactose Natural products 0.000 description 16
- IHKWXDCSAKJQKM-SRQGCSHVSA-N n-[(1s,6s,7r,8r,8ar)-1,7,8-trihydroxy-1,2,3,5,6,7,8,8a-octahydroindolizin-6-yl]acetamide Chemical group O[C@H]1[C@H](O)[C@@H](NC(=O)C)CN2CC[C@H](O)[C@@H]21 IHKWXDCSAKJQKM-SRQGCSHVSA-N 0.000 description 16
- 230000004952 protein activity Effects 0.000 description 16
- -1 imino sugars Chemical class 0.000 description 15
- 150000002632 lipids Chemical class 0.000 description 15
- 210000003712 lysosome Anatomy 0.000 description 15
- 230000001868 lysosomic effect Effects 0.000 description 15
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 14
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 14
- 108010021466 Mutant Proteins Proteins 0.000 description 14
- 102000008300 Mutant Proteins Human genes 0.000 description 14
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 208000001905 GM2 Gangliosidoses Diseases 0.000 description 12
- 201000008905 GM2 gangliosidosis Diseases 0.000 description 12
- 101001045440 Homo sapiens Beta-hexosaminidase subunit alpha Proteins 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 12
- 210000003097 mucus Anatomy 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 102100026189 Beta-galactosidase Human genes 0.000 description 11
- FTSCEGKYKXESFF-LXTVHRRPSA-N N-nonyldeoxynojirimycin Chemical compound CCCCCCCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO FTSCEGKYKXESFF-LXTVHRRPSA-N 0.000 description 11
- QPYJXFZUIJOGNX-HSUXUTPPSA-N afegostat Chemical compound OC[C@H]1CNC[C@@H](O)[C@@H]1O QPYJXFZUIJOGNX-HSUXUTPPSA-N 0.000 description 11
- 108010005774 beta-Galactosidase Proteins 0.000 description 11
- 230000002255 enzymatic effect Effects 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- 150000003408 sphingolipids Chemical class 0.000 description 11
- 229920002527 Glycogen Polymers 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 229940096919 glycogen Drugs 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 208000015872 Gaucher disease Diseases 0.000 description 9
- 102000004157 Hydrolases Human genes 0.000 description 9
- 108090000604 Hydrolases Proteins 0.000 description 9
- 206010072928 Mucolipidosis type II Diseases 0.000 description 9
- 102000012086 alpha-L-Fucosidase Human genes 0.000 description 9
- 108010061314 alpha-L-Fucosidase Proteins 0.000 description 9
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- ZSNFEMNRWFDMNU-CVPUBMOQSA-N (2s,3s,4r,5s,6r)-2-butyl-6-(hydroxymethyl)piperidine-3,4,5-triol Chemical group CCCC[C@@H]1N[C@H](CO)[C@H](O)[C@H](O)[C@H]1O ZSNFEMNRWFDMNU-CVPUBMOQSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- JDVVGAQPNNXQDW-WCMLQCRESA-N Castanospermine Natural products O[C@H]1[C@@H](O)[C@H]2[C@@H](O)CCN2C[C@H]1O JDVVGAQPNNXQDW-WCMLQCRESA-N 0.000 description 8
- JDVVGAQPNNXQDW-TVNFTVLESA-N Castinospermine Chemical compound C1[C@H](O)[C@@H](O)[C@H](O)[C@H]2[C@@H](O)CCN21 JDVVGAQPNNXQDW-TVNFTVLESA-N 0.000 description 8
- 102000053187 Glucuronidase Human genes 0.000 description 8
- 108010060309 Glucuronidase Proteins 0.000 description 8
- 102000003886 Glycoproteins Human genes 0.000 description 8
- 108090000288 Glycoproteins Proteins 0.000 description 8
- ZSNFEMNRWFDMNU-UHFFFAOYSA-N beta-1-C-butyl-deoxygalactonojirimycin Natural products CCCCC1NC(CO)C(O)C(O)C1O ZSNFEMNRWFDMNU-UHFFFAOYSA-N 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical group CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 8
- KNSGUARWFVOEEB-UHFFFAOYSA-N pyrrolo[3,4-d]pyridazin-4-one Chemical group O=C1N=NC=C2C=NC=C12 KNSGUARWFVOEEB-UHFFFAOYSA-N 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- RLJOYSOPEJBIAA-UHFFFAOYSA-N 2-nitro-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C([N+](=O)[O-])CC2=C1 RLJOYSOPEJBIAA-UHFFFAOYSA-N 0.000 description 7
- 208000034012 Acid sphingomyelinase deficiency Diseases 0.000 description 7
- 229920002683 Glycosaminoglycan Polymers 0.000 description 7
- 108010003381 Iduronidase Proteins 0.000 description 7
- 102000004627 Iduronidase Human genes 0.000 description 7
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 description 7
- 125000001931 aliphatic group Chemical group 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 235000012000 cholesterol Nutrition 0.000 description 7
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- UPZUHYMBTUUPML-KBXIAJHMSA-N (1s,2s,3r,6r)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol Chemical compound CCCCCCCCN[C@@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O UPZUHYMBTUUPML-KBXIAJHMSA-N 0.000 description 6
- YRBKDBZXOAEMOT-UHFFFAOYSA-N 6-deoxy-DMDP Natural products CC1NC(CO)C(O)C1O YRBKDBZXOAEMOT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 206010072929 Mucolipidosis type III Diseases 0.000 description 6
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 description 6
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 6
- 102000005348 Neuraminidase Human genes 0.000 description 6
- 108010006232 Neuraminidase Proteins 0.000 description 6
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 6
- 101000718529 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Alpha-galactosidase Proteins 0.000 description 6
- NNISLDGFPWIBDF-MPRBLYSKSA-N alpha-D-Gal-(1->3)-beta-D-Gal-(1->4)-D-GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@@H](CO)O1 NNISLDGFPWIBDF-MPRBLYSKSA-N 0.000 description 6
- 108010012864 alpha-Mannosidase Proteins 0.000 description 6
- 102000019199 alpha-Mannosidase Human genes 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 150000001840 cholesterol esters Chemical class 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 239000007938 effervescent tablet Substances 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 150000004676 glycans Chemical group 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 6
- 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- AXNKITZDVRGIRT-XDQVBPFNSA-N (1R,2S,3S,4S)-1,4-bis(hydroxymethyl)-6-octyl-5-oxa-6-azabicyclo[2.1.1]hexane-2,3-diol Chemical compound C(CCCCCCC)N1[C@]2(CO)[C@@H](O)[C@H](O)[C@]1(O2)CO AXNKITZDVRGIRT-XDQVBPFNSA-N 0.000 description 5
- RMCNETIHECSPMZ-NGQZWQHPSA-N (3s,5r)-piperidine-3,4,5-triol Chemical compound O[C@H]1CNC[C@@H](O)C1O RMCNETIHECSPMZ-NGQZWQHPSA-N 0.000 description 5
- 206010010582 Congenital osteodystrophy Diseases 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 208000007652 Dysostoses Diseases 0.000 description 5
- 201000001324 Dysostosis Diseases 0.000 description 5
- 102100028496 Galactocerebrosidase Human genes 0.000 description 5
- 208000017462 Galactosialidosis Diseases 0.000 description 5
- 102000002464 Galactosidases Human genes 0.000 description 5
- 108010093031 Galactosidases Proteins 0.000 description 5
- 108010042681 Galactosylceramidase Proteins 0.000 description 5
- 206010019842 Hepatomegaly Diseases 0.000 description 5
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 description 5
- 201000000788 Niemann-Pick disease type C1 Diseases 0.000 description 5
- 201000000785 Niemann-Pick disease type C2 Diseases 0.000 description 5
- 201000007100 Pharyngitis Diseases 0.000 description 5
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000012846 protein folding Effects 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 230000006641 stabilisation Effects 0.000 description 5
- 238000011105 stabilization Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 150000008163 sugars Chemical class 0.000 description 5
- 102100032487 Beta-mannosidase Human genes 0.000 description 4
- 208000006029 Cardiomegaly Diseases 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- 206010011777 Cystinosis Diseases 0.000 description 4
- 208000001948 Farber Lipogranulomatosis Diseases 0.000 description 4
- 208000033149 Farber disease Diseases 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 108700037017 Hyaluronidase Deficiency Proteins 0.000 description 4
- 208000005503 Hyaluronidase deficiency Diseases 0.000 description 4
- 108010023320 N-acetylglucosamine-6-sulfatase Proteins 0.000 description 4
- 208000014060 Niemann-Pick disease Diseases 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000027089 Parkinsonian disease Diseases 0.000 description 4
- 206010034010 Parkinsonism Diseases 0.000 description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 4
- 208000024571 Pick disease Diseases 0.000 description 4
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 4
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 description 4
- 206010044565 Tremor Diseases 0.000 description 4
- 108010044965 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase Proteins 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000035508 accumulation Effects 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 108010055059 beta-Mannosidase Proteins 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 4
- 230000003862 health status Effects 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 201000002273 mucopolysaccharidosis II Diseases 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- ZEWFPWKROPWRKE-CQOGJGKDSA-N (2r,3r,4r,5r,6s)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol Chemical compound C[C@@H]1N[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O ZEWFPWKROPWRKE-CQOGJGKDSA-N 0.000 description 3
- YRBKDBZXOAEMOT-DPYQTVNSSA-N (2s,3r,4s,5r)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol Chemical compound C[C@H]1N[C@@H](CO)[C@@H](O)[C@H]1O YRBKDBZXOAEMOT-DPYQTVNSSA-N 0.000 description 3
- YRBKDBZXOAEMOT-VANKVMQKSA-N (2s,3s,4s,5r)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol Chemical compound C[C@H]1N[C@@H](CO)[C@H](O)[C@H]1O YRBKDBZXOAEMOT-VANKVMQKSA-N 0.000 description 3
- LXBIFEVIBLOUGU-FSIIMWSLSA-N 1-Deoxymannojirimycin Natural products OC[C@@H]1NC[C@@H](O)[C@H](O)[C@H]1O LXBIFEVIBLOUGU-FSIIMWSLSA-N 0.000 description 3
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 description 3
- 102100031317 Alpha-N-acetylgalactosaminidase Human genes 0.000 description 3
- 102100034561 Alpha-N-acetylglucosaminidase Human genes 0.000 description 3
- 102100022146 Arylsulfatase A Human genes 0.000 description 3
- 102100031491 Arylsulfatase B Human genes 0.000 description 3
- 108010059081 Cathepsin A Proteins 0.000 description 3
- 102000005572 Cathepsin A Human genes 0.000 description 3
- 102000004171 Cathepsin K Human genes 0.000 description 3
- 108090000625 Cathepsin K Proteins 0.000 description 3
- 108010036867 Cerebroside-Sulfatase Proteins 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001124388 Homo sapiens NPC intracellular cholesterol transporter 1 Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 206010020880 Hypertrophy Diseases 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 description 3
- 102000009565 Lysosomal-Associated Membrane Protein 2 Human genes 0.000 description 3
- 208000027933 Mannosidase Deficiency disease Diseases 0.000 description 3
- 102000001696 Mannosidases Human genes 0.000 description 3
- 108010054377 Mannosidases Proteins 0.000 description 3
- BLOFGONIVNXZME-UHFFFAOYSA-N Mannostatin A Natural products CSC1C(N)C(O)C(O)C1O BLOFGONIVNXZME-UHFFFAOYSA-N 0.000 description 3
- 208000016285 Movement disease Diseases 0.000 description 3
- 206010072930 Mucolipidosis type IV Diseases 0.000 description 3
- 102100026502 Mucolipin-1 Human genes 0.000 description 3
- 206010028372 Muscular weakness Diseases 0.000 description 3
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 3
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 3
- 102000018740 N-Acetylgalactosamine-4-Sulfatase Human genes 0.000 description 3
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 3
- 102100029565 NPC intracellular cholesterol transporter 1 Human genes 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 206010038687 Respiratory distress Diseases 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 102000005262 Sulfatase Human genes 0.000 description 3
- 208000007824 Type A Niemann-Pick Disease Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- DCVWZPYTNWZZIM-UHFFFAOYSA-N alpha-7-deoxyhomonojirimycin Natural products CC1NC(CO)C(O)CC1O DCVWZPYTNWZZIM-UHFFFAOYSA-N 0.000 description 3
- 108010015684 alpha-N-Acetylgalactosaminidase Proteins 0.000 description 3
- 108010009380 alpha-N-acetyl-D-glucosaminidase Proteins 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 238000010322 bone marrow transplantation Methods 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229960002335 bromhexine hydrochloride Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 238000002641 enzyme replacement therapy Methods 0.000 description 3
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical group CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- BLOFGONIVNXZME-YDMGZANHSA-N mannostatin A Chemical compound CS[C@@H]1[C@@H](N)[C@@H](O)[C@@H](O)[C@H]1O BLOFGONIVNXZME-YDMGZANHSA-N 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000003463 organelle Anatomy 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000004043 responsiveness Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 108060007951 sulfatase Proteins 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- FXUAIOOAOAVCGD-UHFFFAOYSA-N swainsonine Natural products C1CCC(O)C2C(O)C(O)CN21 FXUAIOOAOAVCGD-UHFFFAOYSA-N 0.000 description 3
- FXUAIOOAOAVCGD-FKSUSPILSA-N swainsonine Chemical compound C1CC[C@H](O)[C@H]2[C@H](O)[C@H](O)CN21 FXUAIOOAOAVCGD-FKSUSPILSA-N 0.000 description 3
- 229960005566 swainsonine Drugs 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000012096 transfection reagent Substances 0.000 description 3
- 108020005087 unfolded proteins Proteins 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UQRORFVVSGFNRO-XFWSIPNHSA-N (2r,3s,4r,5s)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@@H](O)[C@H]1CO UQRORFVVSGFNRO-XFWSIPNHSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 108020005296 Acid Ceramidase Proteins 0.000 description 2
- 102000006772 Acid Ceramidase Human genes 0.000 description 2
- 108010023546 Aspartylglucosylaminase Proteins 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000027775 Bronchopulmonary disease Diseases 0.000 description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- 230000006782 ER associated degradation Effects 0.000 description 2
- 208000028568 Free sialic acid storage disease Diseases 0.000 description 2
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 208000009796 Gangliosidoses Diseases 0.000 description 2
- 208000020322 Gaucher disease type I Diseases 0.000 description 2
- 208000020916 Gaucher disease type II Diseases 0.000 description 2
- 208000028735 Gaucher disease type III Diseases 0.000 description 2
- 102000004366 Glucosidases Human genes 0.000 description 2
- 108010056771 Glucosidases Proteins 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 229920002971 Heparan sulfate Polymers 0.000 description 2
- 101001122938 Homo sapiens Lysosomal protective protein Proteins 0.000 description 2
- 208000035343 Infantile neurovisceral acid sphingomyelinase deficiency Diseases 0.000 description 2
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-HNFCZKTMSA-N L-idopyranuronic acid Chemical compound OC1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-HNFCZKTMSA-N 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 102000003939 Membrane transport proteins Human genes 0.000 description 2
- 108090000301 Membrane transport proteins Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 102100021003 N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase Human genes 0.000 description 2
- 108010006140 N-sulfoglucosamine sulfohydrolase Proteins 0.000 description 2
- 102100027661 N-sulphoglucosamine sulphohydrolase Human genes 0.000 description 2
- 201000000794 Niemann-Pick disease type A Diseases 0.000 description 2
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 2
- 206010068319 Oropharyngeal pain Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091034057 RNA (poly(A)) Proteins 0.000 description 2
- 102000001424 Ryanodine receptors Human genes 0.000 description 2
- 108091006161 SLC17A5 Proteins 0.000 description 2
- 208000013608 Salla disease Diseases 0.000 description 2
- 208000000828 Sialic Acid Storage Disease Diseases 0.000 description 2
- 208000017460 Sialidosis type 2 Diseases 0.000 description 2
- 201000001828 Sly syndrome Diseases 0.000 description 2
- 206010041660 Splenomegaly Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 2
- 102100038413 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase Human genes 0.000 description 2
- 108010024501 UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase Proteins 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- CLVUFWXGNIFGNC-UHFFFAOYSA-N alpha-homonojirimycin Natural products OCC1NC(CO)C(O)C(O)C1O CLVUFWXGNIFGNC-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- CLVUFWXGNIFGNC-OVHBTUCOSA-N chembl501355 Chemical compound OC[C@H]1N[C@H](CO)[C@H](O)[C@@H](O)[C@@H]1O CLVUFWXGNIFGNC-OVHBTUCOSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 201000006440 gangliosidosis Diseases 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 108010054451 glucosamine acetyltransferase Proteins 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000010370 hearing loss Effects 0.000 description 2
- 231100000888 hearing loss Toxicity 0.000 description 2
- 208000016354 hearing loss disease Diseases 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 201000007769 mucolipidosis Diseases 0.000 description 2
- GBRAQQUMMCVTAV-LXGUWJNJSA-N n-[(3s,4r,5r,6r)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide Chemical compound CC(=O)N[C@H]1CN[C@H](CO)[C@@H](O)[C@@H]1O GBRAQQUMMCVTAV-LXGUWJNJSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 230000008418 synuclein deposition Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- ULBPPCHRAVUQMC-MUMXBIPUSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(3r,4r,5r)-5-(hydroxymethyl)piperidine-3,4-diol Chemical compound OC[C@H]1CNC[C@@H](O)[C@@H]1O.OC(=O)[C@H](O)[C@@H](O)C(O)=O ULBPPCHRAVUQMC-MUMXBIPUSA-N 0.000 description 1
- YIICVSCAKJMMDJ-JTQLQIEISA-N (3s)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-ol Chemical compound C1=CC=C2N=C3[C@@H](O)CCN3CC2=C1 YIICVSCAKJMMDJ-JTQLQIEISA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- HLXHCNWEVQNNKA-UHFFFAOYSA-N 5-methoxy-2,3-dihydro-1h-inden-2-amine Chemical compound COC1=CC=C2CC(N)CC2=C1 HLXHCNWEVQNNKA-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 102100035028 Alpha-L-iduronidase Human genes 0.000 description 1
- 102220486131 Alpha-galactosidase A_E59K_mutation Human genes 0.000 description 1
- 108700023418 Amidases Proteins 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 206010070545 Bacterial translocation Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 240000008564 Boehmeria nivea Species 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010051093 Cardiopulmonary failure Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 208000001573 Cataplexy Diseases 0.000 description 1
- 208000035374 Chronic visceral acid sphingomyelinase deficiency Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 230000009946 DNA mutation Effects 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 208000019749 Eye movement disease Diseases 0.000 description 1
- 108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 description 1
- 102000001390 Fructose-Bisphosphate Aldolase Human genes 0.000 description 1
- 206010056696 Gaze palsy Diseases 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 108010053317 Hexosaminidase A Proteins 0.000 description 1
- 102000016871 Hexosaminidase A Human genes 0.000 description 1
- 102000016870 Hexosaminidase B Human genes 0.000 description 1
- 108010053345 Hexosaminidase B Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101001019502 Homo sapiens Alpha-L-iduronidase Proteins 0.000 description 1
- 101000860415 Homo sapiens Galanin peptides Proteins 0.000 description 1
- 101001004953 Homo sapiens Lysosomal acid lipase/cholesteryl ester hydrolase Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 108010053927 Iduronate Sulfatase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010057180 Liver and spleen enlargement Diseases 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 101710096786 Lysosomal acid alpha-glucosidase Proteins 0.000 description 1
- 102100026001 Lysosomal acid lipase/cholesteryl ester hydrolase Human genes 0.000 description 1
- 208000033868 Lysosomal disease Diseases 0.000 description 1
- 102100028524 Lysosomal protective protein Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
- 208000028781 Mucopolysaccharidosis type 1 Diseases 0.000 description 1
- 208000025915 Mucopolysaccharidosis type 6 Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 108091006036 N-glycosylated proteins Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108700018419 Niemann-Pick C1 Proteins 0.000 description 1
- 201000000791 Niemann-Pick disease type B Diseases 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
- 208000010346 Sphingolipidoses Diseases 0.000 description 1
- 201000001307 Sphingolipidosis Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 208000008291 Type B Niemann-Pick Disease Diseases 0.000 description 1
- 206010069555 Use of accessory respiratory muscles Diseases 0.000 description 1
- 208000026589 Wolman disease Diseases 0.000 description 1
- 108010070626 acid beta-galactosidase Proteins 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 208000016150 acute pharyngitis Diseases 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 description 1
- 102000003802 alpha-Synuclein Human genes 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000002588 alveolar type II cell Anatomy 0.000 description 1
- 229960000985 ambroxol hydrochloride Drugs 0.000 description 1
- 102000005922 amidase Human genes 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000010065 bacterial adhesion Effects 0.000 description 1
- 230000007375 bacterial translocation Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 108010085377 beta-N-Acetylhexosaminidases Proteins 0.000 description 1
- 102000007478 beta-N-Acetylhexosaminidases Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006800 cellular catabolic process Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000010405 clearance mechanism Effects 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000006517 essential tremor Diseases 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 210000001097 facial muscle Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 description 1
- GIVLTTJNORAZON-HDBOBKCLSA-N ganglioside GM2 (18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 GIVLTTJNORAZON-HDBOBKCLSA-N 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 230000002430 glycogenolytic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 238000011850 initial investigation Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960001512 miglustat Drugs 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 208000000690 mucopolysaccharidosis VI Diseases 0.000 description 1
- 238000001964 muscle biopsy Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 208000028780 ocular motility disease Diseases 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 208000026526 progressive weakness Diseases 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 108020001775 protein parts Proteins 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 238000006338 pulse radiolysis reaction Methods 0.000 description 1
- 229960000611 pyrimethamine Drugs 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000003019 respiratory muscle Anatomy 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 230000006829 sphingolipid biosynthesis Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000007855 transport deficit Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229940099072 zavesca Drugs 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11010078.1 | 2011-12-22 | ||
| EP11010078 | 2011-12-22 | ||
| PCT/EP2012/005363 WO2013091897A1 (en) | 2011-12-22 | 2012-12-21 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017248953A Division JP2018076353A (ja) | 2011-12-22 | 2017-12-26 | リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015502964A JP2015502964A (ja) | 2015-01-29 |
| JP2015502964A5 JP2015502964A5 (https=) | 2016-01-28 |
| JP6320931B2 true JP6320931B2 (ja) | 2018-05-09 |
Family
ID=47559375
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014547767A Expired - Fee Related JP6320931B2 (ja) | 2011-12-22 | 2012-12-21 | リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ |
| JP2017248953A Pending JP2018076353A (ja) | 2011-12-22 | 2017-12-26 | リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017248953A Pending JP2018076353A (ja) | 2011-12-22 | 2017-12-26 | リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20150258081A1 (https=) |
| EP (1) | EP2793872B1 (https=) |
| JP (2) | JP6320931B2 (https=) |
| KR (1) | KR102076585B1 (https=) |
| AU (2) | AU2012359165A1 (https=) |
| BR (1) | BR112014014808A2 (https=) |
| CA (1) | CA2860085A1 (https=) |
| ES (1) | ES2864774T3 (https=) |
| IL (1) | IL233173B (https=) |
| WO (1) | WO2013091897A1 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9675627B2 (en) * | 2014-04-14 | 2017-06-13 | Amicus Therapeutics, Inc. | Dosing regimens for treating and/or preventing cerebral amyloidoses |
| CN114540327B (zh) | 2014-09-30 | 2026-03-24 | 阿米库斯治疗学公司 | 具有增强的碳水化合物的高强度酸性α-葡糖苷酶 |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| JP6981961B2 (ja) * | 2015-07-30 | 2021-12-17 | ホライズン オルファン エルエルシー | フコシダーゼ阻害剤 |
| KR20250007693A (ko) | 2015-12-30 | 2025-01-14 | 아미쿠스 세라퓨틱스, 인코포레이티드 | 폼페병 치료용의 강화된 산 알파-글루코시다제 |
| KR20190087673A (ko) | 2016-03-22 | 2019-07-24 | 아미쿠스 세라퓨틱스, 인코포레이티드 | Ｇｌａ 유전자에 ｇ9331ａ 돌연변이를 갖는 환자에서 파브리 질병의 치료 방법 |
| CA3019354A1 (en) | 2016-03-30 | 2017-10-05 | Amicus Therapeutics, Inc. | Method for selection of high m6p recombinant proteins |
| AU2017239641A1 (en) | 2016-03-30 | 2018-10-18 | Amicus Therapeutics, Inc. | Formulations comprising recombinant acid alpha-glucosidase |
| US20190254992A1 (en) * | 2016-06-29 | 2019-08-22 | Hadasit Medical Research Services & Development Limited | Combinations of beta-glycolipides and 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol, compositions and uses thereof in the treatment of disorders associated with protein misfolding and protein aggregations |
| WO2018089797A1 (en) * | 2016-11-14 | 2018-05-17 | Mingwu Wang | Formulations for the treatment of ocular surface diseases and related methods |
| CN110573492A (zh) * | 2017-04-25 | 2019-12-13 | 阿米库斯治疗学公司 | 用于预防和/或治疗中枢神经系统退行性失调和/或溶酶体贮积失调的新颖组合物 |
| SMT202300187T1 (it) | 2017-05-15 | 2023-07-20 | Amicus Therapeutics Inc | Alfa-glucosidasi acida umana ricombinante |
| CA3224546C (en) | 2017-05-30 | 2026-02-24 | Amicus Therapeutics, Inc. | Use of migalastat in the treatment of fabry patients |
| US20220184185A1 (en) | 2018-07-25 | 2022-06-16 | Modernatx, Inc. | Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders |
| US12594268B2 (en) | 2018-08-20 | 2026-04-07 | Amicus Therapeutics, Inc. | Methods of treating Fabry disease in patients having a mutation in the GLA gene |
| US11612619B2 (en) | 2018-11-01 | 2023-03-28 | National Institute Of Health (Nih), U.S. Dept. Of Health And Human Services (Dhhs), U.S. Government | Compostions and methods for enabling cholesterol catabolism in human cells |
| EP3884383B1 (en) * | 2018-12-21 | 2025-04-16 | Shenzhen Yinwang Intelligent Technologies Co., Ltd. | Data deterministic deliverable communication technology based on qos as a service |
| WO2020168294A1 (en) * | 2019-02-15 | 2020-08-20 | Lysosomal And Rare Disorders Research And Treatment Center, Llc | Methods and compositions for treating lysosomal storage disorders: ambroxol as treatment agent for mucopolysaccharidoses iii (sanfilippo syndrome) |
| EP3996696A1 (en) * | 2019-07-09 | 2022-05-18 | Genethon | Treatment of glycogen storage disease (gsd) |
| KR20220044560A (ko) | 2019-08-07 | 2022-04-08 | 아미쿠스 세라퓨틱스, 인코포레이티드 | Gla 유전자에 돌연변이를 갖는 환자에서 파브리 질병을 치료하는 방법 |
| US12544402B2 (en) | 2020-02-28 | 2026-02-10 | Repair Biotechnologies, Inc. | Targeted expression of microbial cholesterol catalysis genes reduces excess lipid |
| CN112773779B (zh) * | 2021-02-04 | 2022-08-16 | 上海交通大学医学院附属新华医院 | 氨溴索、千金藤和汉防已在治疗酸性鞘磷脂酶缺乏症中的应用 |
| CN114644572B (zh) * | 2022-03-22 | 2023-03-28 | 华南农业大学 | 一种溴己新半抗原、人工抗原、抗体及其制备方法和应用 |
| KR20260002803A (ko) * | 2023-05-02 | 2026-01-06 | 지위, 엘엘씨 | 치료적 사용을 위한 암브록솔의 변형된 형태 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19933148A1 (de) | 1999-07-20 | 2001-01-25 | Boehringer Ingelheim Int | Ambroxolhaltige Lutschtablette |
| EP2857036B1 (en) * | 2003-01-31 | 2016-12-21 | Mount Sinai School of Medicine of New York University | Combination therapy for treating protein deficiency disorders |
| PL2533050T6 (pl) * | 2006-05-16 | 2016-05-31 | Amicus Therapeutics Inc | Możliwości leczenia choroby Fabry'ego |
| JP5337405B2 (ja) * | 2007-09-17 | 2013-11-06 | ザ・ホスピタル・フォー・シック・チルドレン | ゴーシェ病の治療方法 |
| CA2718182A1 (en) * | 2008-03-12 | 2009-09-17 | Amicus Therapeutics, Inc. | Treatment of pompe disease with specific pharmacological chaperones and monitoring treatment using surrogate markers |
| EP2353403B1 (de) * | 2010-02-01 | 2012-07-11 | Symrise AG | Verwendung von 1-(2,4-Dihydroxy-phenyl)-3-(3-hydroxy-4-methoxy-phenyl)-propan-1-on |
-
2012
- 2012-12-21 KR KR1020147019849A patent/KR102076585B1/ko not_active Expired - Fee Related
- 2012-12-21 US US14/367,835 patent/US20150258081A1/en not_active Abandoned
- 2012-12-21 CA CA2860085A patent/CA2860085A1/en not_active Abandoned
- 2012-12-21 EP EP12815644.5A patent/EP2793872B1/en not_active Not-in-force
- 2012-12-21 AU AU2012359165A patent/AU2012359165A1/en not_active Abandoned
- 2012-12-21 ES ES12815644T patent/ES2864774T3/es active Active
- 2012-12-21 JP JP2014547767A patent/JP6320931B2/ja not_active Expired - Fee Related
- 2012-12-21 WO PCT/EP2012/005363 patent/WO2013091897A1/en not_active Ceased
- 2012-12-21 BR BR112014014808A patent/BR112014014808A2/pt not_active Application Discontinuation
-
2014
- 2014-06-16 IL IL233173A patent/IL233173B/en active IP Right Grant
-
2017
- 2017-12-22 AU AU2017279780A patent/AU2017279780B2/en not_active Ceased
- 2017-12-26 JP JP2017248953A patent/JP2018076353A/ja active Pending
-
2021
- 2021-04-05 US US17/222,254 patent/US20210228560A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20210228560A1 (en) | 2021-07-29 |
| AU2012359165A1 (en) | 2014-07-10 |
| EP2793872B1 (en) | 2021-03-10 |
| AU2017279780A1 (en) | 2018-01-25 |
| ES2864774T3 (es) | 2021-10-14 |
| IL233173A0 (en) | 2014-07-31 |
| KR20140107481A (ko) | 2014-09-04 |
| AU2017279780B2 (en) | 2019-10-03 |
| EP2793872A1 (en) | 2014-10-29 |
| KR102076585B1 (ko) | 2020-02-12 |
| WO2013091897A8 (en) | 2014-10-09 |
| BR112014014808A2 (pt) | 2018-09-25 |
| JP2015502964A (ja) | 2015-01-29 |
| IL233173B (en) | 2020-10-29 |
| CA2860085A1 (en) | 2013-06-27 |
| JP2018076353A (ja) | 2018-05-17 |
| WO2013091897A1 (en) | 2013-06-27 |
| US20150258081A1 (en) | 2015-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6320931B2 (ja) | リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ | |
| Platt et al. | Lysosomal storage diseases | |
| Beck | New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy | |
| JP6546923B2 (ja) | リソソーム蓄積障害または糖原病の処置における使用のためのエキソサイトーシス活性化化合物としてのビカルタミド類似体または（ｓ）−ビカルタミド | |
| KR102412724B1 (ko) | 리소좀 축적 질환과 관련된 약제 조성물 및 용도 | |
| M Wrodnigg et al. | The two faces of iminoalditols: powerful inhibitors trigger glycosidase activation | |
| EP3989962B1 (en) | Combination therapy with acetyl-leucine and miglustat for treating a lysosomal storage disease | |
| US20180326021A1 (en) | Methods and Compositions for the Treatment of Cytoplasmic Glycogen Storage Disorders | |
| US20170196842A1 (en) | Methods of treatment using a 1,2,4-oxadiazole benzoic acid | |
| Matassini et al. | Carbohydrate‐Based Therapeutics for Lysosomal Storage Disorders | |
| EP4349334A1 (en) | Palatable liquid solution containing high concentration of miglustat | |
| JP6857648B2 (ja) | リソソーム障害及び中枢神経系の変性障害の治療及び予防のための（３ｒ，４ｒ，５ｓ）−５−（ジフルオロメチル）ピペリジン−３，４−ジオールを含むレジメン | |
| HK40127928A (en) | Combination therapy with acetyl-leucine and miglustat for treating a lysosomal storage disease | |
| RU2853626C2 (ru) | Фармацевтические композиции и применения против лизосомных болезней накопления | |
| WO2014102417A1 (es) | UTILIZACIÓN DE DERIVADOS BICÍCLICOS DE 1-DESOXIGALACTONOJIRIMICINA EN LA PREPARACIÓN DE UN MEDICAMENTO PARA EL TRATAMIENTO DE ENFERMEDADES RELACIONADAS CON ß-ENZIMAS GALACTOSIDASAS LISOSÓMICAS MUTANTES HUMANAS | |
| HK1226945B (zh) | 用於在溶酶体贮积症或糖原贮积病的治疗中使用的作为胞吐作用活化化合物的比卡鲁胺类似物或(s)-比卡鲁胺 | |
| BR112019002719B1 (pt) | Uso de uma acetil-leucina ou um sal farmaceuticamente aceitável da mesma |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20150529 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151201 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151201 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20161017 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161220 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170224 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170414 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20170830 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171226 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20171226 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20180123 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180112 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180220 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20180220 |
|
| 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: 20180315 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180404 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6320931 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |