RU2626514C2 - Доставка к цнс лечебных агентов - Google Patents
Доставка к цнс лечебных агентов Download PDFInfo
- Publication number
- RU2626514C2 RU2626514C2 RU2012154831A RU2012154831A RU2626514C2 RU 2626514 C2 RU2626514 C2 RU 2626514C2 RU 2012154831 A RU2012154831 A RU 2012154831A RU 2012154831 A RU2012154831 A RU 2012154831A RU 2626514 C2 RU2626514 C2 RU 2626514C2
- Authority
- RU
- Russia
- Prior art keywords
- brain
- tissue
- enzyme
- nmol
- disease
- Prior art date
Links
- 238000012384 transportation and delivery Methods 0.000 title claims abstract description 108
- 210000003169 central nervous system Anatomy 0.000 title claims description 79
- 102000004190 Enzymes Human genes 0.000 claims abstract description 274
- 108090000790 Enzymes Proteins 0.000 claims abstract description 274
- 238000007913 intrathecal administration Methods 0.000 claims abstract description 274
- 238000000034 method Methods 0.000 claims abstract description 156
- 239000000203 mixture Substances 0.000 claims abstract description 154
- 238000011282 treatment Methods 0.000 claims abstract description 101
- 230000000694 effects Effects 0.000 claims abstract description 83
- 230000002132 lysosomal effect Effects 0.000 claims abstract description 82
- 208000015439 Lysosomal storage disease Diseases 0.000 claims abstract description 73
- 230000007423 decrease Effects 0.000 claims abstract description 63
- 239000000126 substance Substances 0.000 claims abstract description 41
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 37
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 35
- 239000010452 phosphate Substances 0.000 claims abstract description 35
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims abstract description 29
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 claims abstract description 23
- 201000002273 mucopolysaccharidosis II Diseases 0.000 claims abstract description 20
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 claims abstract description 10
- 208000028226 Krabbe disease Diseases 0.000 claims abstract description 10
- 210000001519 tissue Anatomy 0.000 claims description 326
- 210000004556 brain Anatomy 0.000 claims description 282
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 117
- 201000010099 disease Diseases 0.000 claims description 107
- 210000000278 spinal cord Anatomy 0.000 claims description 98
- 108090000623 proteins and genes Proteins 0.000 claims description 89
- 102000004169 proteins and genes Human genes 0.000 claims description 84
- 210000004027 cell Anatomy 0.000 claims description 75
- 210000005013 brain tissue Anatomy 0.000 claims description 74
- 238000001990 intravenous administration Methods 0.000 claims description 70
- 210000004885 white matter Anatomy 0.000 claims description 61
- 210000004185 liver Anatomy 0.000 claims description 54
- 210000002569 neuron Anatomy 0.000 claims description 52
- 210000003734 kidney Anatomy 0.000 claims description 51
- 208000024891 symptom Diseases 0.000 claims description 48
- 108010089932 heparan sulfate sulfatase Proteins 0.000 claims description 38
- 238000009825 accumulation Methods 0.000 claims description 37
- 210000003710 cerebral cortex Anatomy 0.000 claims description 36
- 102100022146 Arylsulfatase A Human genes 0.000 claims description 35
- 108010036867 Cerebroside-Sulfatase Proteins 0.000 claims description 35
- 210000001638 cerebellum Anatomy 0.000 claims description 34
- 210000002216 heart Anatomy 0.000 claims description 32
- 210000003712 lysosome Anatomy 0.000 claims description 30
- 230000002093 peripheral effect Effects 0.000 claims description 30
- 239000012634 fragment Substances 0.000 claims description 29
- 230000001868 lysosomic effect Effects 0.000 claims description 28
- 210000004884 grey matter Anatomy 0.000 claims description 27
- 210000000952 spleen Anatomy 0.000 claims description 27
- 208000011580 syndromic disease Diseases 0.000 claims description 24
- 238000009472 formulation Methods 0.000 claims description 22
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 claims description 20
- 208000008955 Mucolipidoses Diseases 0.000 claims description 20
- 210000000133 brain stem Anatomy 0.000 claims description 20
- 210000000449 purkinje cell Anatomy 0.000 claims description 20
- 230000002490 cerebral effect Effects 0.000 claims description 19
- 210000004705 lumbosacral region Anatomy 0.000 claims description 19
- 210000001103 thalamus Anatomy 0.000 claims description 19
- 230000001965 increasing effect Effects 0.000 claims description 17
- 101710096421 Iduronate 2-sulfatase Proteins 0.000 claims description 16
- 230000002255 enzymatic effect Effects 0.000 claims description 16
- 210000004379 membrane Anatomy 0.000 claims description 16
- 210000000877 corpus callosum Anatomy 0.000 claims description 15
- 239000012528 membrane Substances 0.000 claims description 15
- 210000004498 neuroglial cell Anatomy 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 108010005774 beta-Galactosidase Proteins 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 210000000056 organ Anatomy 0.000 claims description 11
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 claims description 10
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 10
- 208000010877 cognitive disease Diseases 0.000 claims description 10
- 239000002052 molecular layer Substances 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- 208000028698 Cognitive impairment Diseases 0.000 claims description 8
- 108010009380 alpha-N-acetyl-D-glucosaminidase Proteins 0.000 claims description 8
- 210000003050 axon Anatomy 0.000 claims description 8
- 210000003446 pia mater Anatomy 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 8
- 102100034561 Alpha-N-acetylglucosaminidase Human genes 0.000 claims description 7
- 208000001905 GM2 Gangliosidoses Diseases 0.000 claims description 7
- 201000008905 GM2 gangliosidosis Diseases 0.000 claims description 7
- 101001045440 Homo sapiens Beta-hexosaminidase subunit alpha Proteins 0.000 claims description 7
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 7
- 230000015556 catabolic process Effects 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 7
- 206010012559 Developmental delay Diseases 0.000 claims description 6
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 6
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 6
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
- 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 claims description 6
- 238000006731 degradation reaction Methods 0.000 claims description 6
- 230000000750 progressive effect Effects 0.000 claims description 6
- 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 claims description 6
- 206010003694 Atrophy Diseases 0.000 claims description 5
- 208000016192 Demyelinating disease Diseases 0.000 claims description 5
- 206010012305 Demyelination Diseases 0.000 claims description 5
- 208000015872 Gaucher disease Diseases 0.000 claims description 5
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 claims description 5
- 210000000576 arachnoid Anatomy 0.000 claims description 5
- 230000037444 atrophy Effects 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 208000016354 hearing loss disease Diseases 0.000 claims description 5
- 238000002650 immunosuppressive therapy Methods 0.000 claims description 5
- 210000004786 perivascular cell Anatomy 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 206010011777 Cystinosis Diseases 0.000 claims description 4
- 206010011878 Deafness Diseases 0.000 claims description 4
- 208000024720 Fabry Disease Diseases 0.000 claims description 4
- 208000017462 Galactosialidosis Diseases 0.000 claims description 4
- 229920002527 Glycogen Polymers 0.000 claims description 4
- 208000026589 Wolman disease Diseases 0.000 claims description 4
- 201000006486 beta-mannosidosis Diseases 0.000 claims description 4
- 201000008049 fucosidosis Diseases 0.000 claims description 4
- 108020001507 fusion proteins Proteins 0.000 claims description 4
- 102000037865 fusion proteins Human genes 0.000 claims description 4
- 210000000609 ganglia Anatomy 0.000 claims description 4
- 229940096919 glycogen Drugs 0.000 claims description 4
- 208000036546 leukodystrophy Diseases 0.000 claims description 4
- 201000007769 mucolipidosis Diseases 0.000 claims description 4
- 208000036710 mucopolysaccharidosis type 3A Diseases 0.000 claims description 4
- 208000036709 mucopolysaccharidosis type 3B Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000031277 Amaurotic familial idiocy Diseases 0.000 claims description 3
- 206010068220 Aspartylglucosaminuria Diseases 0.000 claims description 3
- 201000004569 Blindness Diseases 0.000 claims description 3
- 208000001948 Farber Lipogranulomatosis Diseases 0.000 claims description 3
- 201000008892 GM1 Gangliosidosis Diseases 0.000 claims description 3
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims description 3
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims description 3
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims description 3
- 208000036626 Mental retardation Diseases 0.000 claims description 3
- 206010072927 Mucolipidosis type I Diseases 0.000 claims description 3
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 claims description 3
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 3
- 208000022292 Tay-Sachs disease Diseases 0.000 claims description 3
- 210000001951 dura mater Anatomy 0.000 claims description 3
- 201000004502 glycogen storage disease II Diseases 0.000 claims description 3
- 201000008977 glycoproteinosis Diseases 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 208000003906 hydrocephalus Diseases 0.000 claims description 3
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- 208000036725 mucopolysaccharidosis type 3D Diseases 0.000 claims description 3
- 210000003007 myelin sheath Anatomy 0.000 claims description 3
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 claims description 3
- 201000007642 neuronal ceroid lipofuscinosis 1 Diseases 0.000 claims description 3
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 3
- 229940068977 polysorbate 20 Drugs 0.000 claims description 3
- 238000002203 pretreatment Methods 0.000 claims description 3
- 201000010108 pycnodysostosis Diseases 0.000 claims description 3
- 208000011985 sialidosis Diseases 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000022925 sleep disturbance Diseases 0.000 claims description 3
- 210000001835 viscera Anatomy 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 2
- 206010008096 Cerebral atrophy Diseases 0.000 claims description 2
- 208000025127 Erdheim-Chester disease Diseases 0.000 claims description 2
- 229930186217 Glycolipid Natural products 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 206010062016 Immunosuppression Diseases 0.000 claims description 2
- 206010022773 Intracranial pressure increased Diseases 0.000 claims description 2
- 206010022998 Irritability Diseases 0.000 claims description 2
- 206010061296 Motor dysfunction Diseases 0.000 claims description 2
- 208000025797 Mucopolysaccharidosis type 4A Diseases 0.000 claims description 2
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 2
- 206010044565 Tremor Diseases 0.000 claims description 2
- 206010047700 Vomiting Diseases 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- 208000024042 cholesterol ester storage disease Diseases 0.000 claims description 2
- 208000013760 cholesteryl ester storage disease Diseases 0.000 claims description 2
- 231100000895 deafness Toxicity 0.000 claims description 2
- 230000001667 episodic effect Effects 0.000 claims description 2
- 230000010370 hearing loss Effects 0.000 claims description 2
- 231100000888 hearing loss Toxicity 0.000 claims description 2
- 208000013403 hyperactivity Diseases 0.000 claims description 2
- 230000003340 mental effect Effects 0.000 claims description 2
- 208000020468 mucolipidosis III alpha/beta Diseases 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 208000018198 spasticity Diseases 0.000 claims description 2
- 238000012385 systemic delivery Methods 0.000 claims description 2
- 230000008673 vomiting Effects 0.000 claims description 2
- 102000005936 beta-Galactosidase Human genes 0.000 claims 4
- 206010001488 Aggression Diseases 0.000 claims 1
- 206010020852 Hypertonia Diseases 0.000 claims 1
- 208000027933 Mannosidase Deficiency disease Diseases 0.000 claims 1
- 206010072929 Mucolipidosis type III Diseases 0.000 claims 1
- 210000000219 ependymocyte Anatomy 0.000 claims 1
- 230000009610 hypersensitivity Effects 0.000 claims 1
- 208000020004 mucopolysaccharidosis type 9 Diseases 0.000 claims 1
- 210000004872 soft tissue Anatomy 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 121
- 208000005340 mucopolysaccharidosis III Diseases 0.000 abstract description 14
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 abstract description 8
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 229940088598 enzyme Drugs 0.000 description 229
- 241001465754 Metazoa Species 0.000 description 151
- 238000002347 injection Methods 0.000 description 138
- 239000007924 injection Substances 0.000 description 138
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 120
- 229940124597 therapeutic agent Drugs 0.000 description 90
- 235000018102 proteins Nutrition 0.000 description 82
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 78
- 210000002966 serum Anatomy 0.000 description 75
- 239000008280 blood Substances 0.000 description 71
- 210000004369 blood Anatomy 0.000 description 69
- 241000699670 Mus sp. Species 0.000 description 57
- 235000002639 sodium chloride Nutrition 0.000 description 53
- 238000010186 staining Methods 0.000 description 47
- 230000001225 therapeutic effect Effects 0.000 description 43
- 239000011780 sodium chloride Substances 0.000 description 42
- 241000700159 Rattus Species 0.000 description 38
- 230000035508 accumulation Effects 0.000 description 33
- 239000002552 dosage form Substances 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- 210000003743 erythrocyte Anatomy 0.000 description 31
- 239000008194 pharmaceutical composition Substances 0.000 description 31
- 229940079593 drug Drugs 0.000 description 29
- 101150022753 galc gene Proteins 0.000 description 28
- 210000000813 small intestine Anatomy 0.000 description 28
- 241000282693 Cercopithecidae Species 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 26
- 210000001072 colon Anatomy 0.000 description 26
- 238000012744 immunostaining Methods 0.000 description 26
- 210000004072 lung Anatomy 0.000 description 26
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 25
- 101710116782 Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 25
- 210000002784 stomach Anatomy 0.000 description 25
- 239000010410 layer Substances 0.000 description 24
- 235000021317 phosphate Nutrition 0.000 description 24
- 230000002739 subcortical effect Effects 0.000 description 24
- 210000001685 thyroid gland Anatomy 0.000 description 23
- 210000004100 adrenal gland Anatomy 0.000 description 22
- 239000000872 buffer Substances 0.000 description 22
- 210000003497 sciatic nerve Anatomy 0.000 description 22
- 238000013222 sprague-dawley male rat Methods 0.000 description 22
- 210000001508 eye Anatomy 0.000 description 21
- 230000037396 body weight Effects 0.000 description 20
- 210000000115 thoracic cavity Anatomy 0.000 description 20
- 230000006870 function Effects 0.000 description 19
- 210000003205 muscle Anatomy 0.000 description 19
- 150000001413 amino acids Chemical group 0.000 description 18
- 230000000875 corresponding effect Effects 0.000 description 18
- 230000000849 parathyroid Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 210000000577 adipose tissue Anatomy 0.000 description 17
- 238000009826 distribution Methods 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 238000003860 storage Methods 0.000 description 17
- 229920002683 Glycosaminoglycan Polymers 0.000 description 16
- 230000007812 deficiency Effects 0.000 description 15
- 239000012530 fluid Substances 0.000 description 15
- 238000005259 measurement Methods 0.000 description 15
- 238000011887 Necropsy Methods 0.000 description 14
- 230000006872 improvement Effects 0.000 description 14
- 239000007788 liquid Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 13
- 235000001014 amino acid Nutrition 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 210000000689 upper leg Anatomy 0.000 description 13
- 230000003442 weekly effect Effects 0.000 description 13
- 229920002971 Heparan sulfate Polymers 0.000 description 12
- 102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 12
- 108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 12
- 210000004940 nucleus Anatomy 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 210000003932 urinary bladder Anatomy 0.000 description 12
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 description 11
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 11
- 241000282567 Macaca fascicularis Species 0.000 description 11
- 210000002418 meninge Anatomy 0.000 description 11
- 229920001542 oligosaccharide Polymers 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- 239000013049 sediment Substances 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 210000001159 caudate nucleus Anatomy 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 210000001035 gastrointestinal tract Anatomy 0.000 description 10
- 238000011532 immunohistochemical staining Methods 0.000 description 10
- 241000282553 Macaca Species 0.000 description 9
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 238000001647 drug administration Methods 0.000 description 9
- 210000001320 hippocampus Anatomy 0.000 description 9
- 230000002055 immunohistochemical effect Effects 0.000 description 9
- 238000001802 infusion Methods 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 230000002285 radioactive effect Effects 0.000 description 9
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 9
- 102100026189 Beta-galactosidase Human genes 0.000 description 8
- -1 Fucosyl oligosaccharides Chemical class 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 230000008499 blood brain barrier function Effects 0.000 description 8
- 210000001218 blood-brain barrier Anatomy 0.000 description 8
- 230000002950 deficient Effects 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000002641 enzyme replacement therapy Methods 0.000 description 8
- 230000028993 immune response Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 150000007523 nucleic acids Chemical class 0.000 description 8
- 210000004248 oligodendroglia Anatomy 0.000 description 8
- 150000002482 oligosaccharides Chemical class 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 238000011084 recovery Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 108060007951 sulfatase Proteins 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 208000012902 Nervous system disease Diseases 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 7
- 238000011888 autopsy Methods 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 210000003736 gastrointestinal content Anatomy 0.000 description 7
- 239000003018 immunosuppressive agent Substances 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 210000001259 mesencephalon Anatomy 0.000 description 7
- HHJTWTPUPVQKNA-PIIMIWFASA-N psychosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O HHJTWTPUPVQKNA-PIIMIWFASA-N 0.000 description 7
- 239000001488 sodium phosphate Substances 0.000 description 7
- 229910000162 sodium phosphate Inorganic materials 0.000 description 7
- 239000003381 stabilizer Substances 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 6
- 210000004958 brain cell Anatomy 0.000 description 6
- 230000004700 cellular uptake Effects 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- HHJTWTPUPVQKNA-UHFFFAOYSA-N psychosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)COC1OC(CO)C(O)C(O)C1O HHJTWTPUPVQKNA-UHFFFAOYSA-N 0.000 description 6
- 239000000941 radioactive substance Substances 0.000 description 6
- 210000004974 shell Anatomy 0.000 description 6
- 210000003625 skull Anatomy 0.000 description 6
- 238000004611 spectroscopical analysis Methods 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 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 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 229920000045 Dermatan sulfate Polymers 0.000 description 5
- 102100028496 Galactocerebrosidase Human genes 0.000 description 5
- 108010042681 Galactosylceramidase Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 208000033868 Lysosomal disease Diseases 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 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 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 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 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 159000000007 calcium salts Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 235000011089 carbon dioxide Nutrition 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 210000003979 eosinophil Anatomy 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- 210000003016 hypothalamus Anatomy 0.000 description 5
- 230000006058 immune tolerance Effects 0.000 description 5
- 238000000185 intracerebroventricular administration Methods 0.000 description 5
- 210000003292 kidney cell Anatomy 0.000 description 5
- 229920002521 macromolecule Polymers 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 238000001000 micrograph Methods 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 210000002990 parathyroid gland Anatomy 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 238000005070 sampling Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- OEANUJAFZLQYOD-CXAZCLJRSA-N (2r,3s,4r,5r,6r)-6-[(2r,3r,4r,5r,6r)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](OC)O[C@H](CO)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC)[C@H](C(O)=O)O1 OEANUJAFZLQYOD-CXAZCLJRSA-N 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 4
- 102000009133 Arylsulfatases Human genes 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 102000005262 Sulfatase Human genes 0.000 description 4
- 230000006838 adverse reaction Effects 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 210000002451 diencephalon Anatomy 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 230000007613 environmental effect Effects 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 108010072166 idursulfase Proteins 0.000 description 4
- 229960002396 idursulfase Drugs 0.000 description 4
- 229940125721 immunosuppressive agent Drugs 0.000 description 4
- 230000006057 immunotolerant effect Effects 0.000 description 4
- 239000000644 isotonic solution Substances 0.000 description 4
- 210000002414 leg Anatomy 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 210000005229 liver cell Anatomy 0.000 description 4
- 210000000274 microglia Anatomy 0.000 description 4
- 210000003463 organelle Anatomy 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 4
- 239000008177 pharmaceutical agent Substances 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 229920001983 poloxamer Polymers 0.000 description 4
- 230000000392 somatic effect Effects 0.000 description 4
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- 210000003934 vacuole Anatomy 0.000 description 4
- 208000029602 Alpha-N-acetylgalactosaminidase deficiency Diseases 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 229930105110 Cyclosporin A Natural products 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 3
- 102100036089 Fascin Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000038460 IGF Type 2 Receptor Human genes 0.000 description 3
- 108010031792 IGF Type 2 Receptor Proteins 0.000 description 3
- 102000004627 Iduronidase Human genes 0.000 description 3
- 108010003381 Iduronidase Proteins 0.000 description 3
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 3
- 229960001736 buprenorphine Drugs 0.000 description 3
- 210000003591 cerebellar nuclei Anatomy 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 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 3
- 230000001434 glomerular Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 210000002570 interstitial cell Anatomy 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 229960002725 isoflurane Drugs 0.000 description 3
- 239000007951 isotonicity adjuster Substances 0.000 description 3
- 125000005645 linoleyl group Chemical group 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 description 3
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- DDOVBCWVTOHGCU-QMXMISKISA-N n-[(e,2s,3r)-3-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxynonadec-4-en-2-yl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O DDOVBCWVTOHGCU-QMXMISKISA-N 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 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 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102100027165 Alpha-2-macroglobulin receptor-associated protein Human genes 0.000 description 2
- 101710126837 Alpha-2-macroglobulin receptor-associated protein Proteins 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 101710124976 Beta-hexosaminidase A Proteins 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 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
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 208000028782 Hereditary disease Diseases 0.000 description 2
- 101000901140 Homo sapiens Arylsulfatase A Proteins 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- 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 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000037490 Medically Unexplained Symptoms Diseases 0.000 description 2
- 208000024556 Mendelian disease Diseases 0.000 description 2
- 206010072928 Mucolipidosis type II Diseases 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 235000014443 Pyrus communis Nutrition 0.000 description 2
- 208000021811 Sandhoff disease Diseases 0.000 description 2
- 208000025816 Sanfilippo syndrome type A Diseases 0.000 description 2
- 208000025820 Sanfilippo syndrome type B Diseases 0.000 description 2
- 208000017460 Sialidosis type 2 Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 2
- 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 2
- 210000004727 amygdala Anatomy 0.000 description 2
- 238000013103 analytical ultracentrifugation Methods 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000003766 bioinformatics method Methods 0.000 description 2
- 208000024330 bloating Diseases 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 239000005388 borosilicate glass Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 229940106189 ceramide Drugs 0.000 description 2
- 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 2
- 210000003198 cerebellar cortex Anatomy 0.000 description 2
- 210000004289 cerebral ventricle Anatomy 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 210000003792 cranial nerve Anatomy 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 229940050526 hydroxyethylstarch Drugs 0.000 description 2
- 239000000819 hypertonic solution Substances 0.000 description 2
- 229940021223 hypertonic solution Drugs 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000005230 lumbar spinal cord Anatomy 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000007491 morphometric analysis Methods 0.000 description 2
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 description 2
- 208000012226 mucopolysaccharidosis type IIIA Diseases 0.000 description 2
- 208000012227 mucopolysaccharidosis type IIIB Diseases 0.000 description 2
- 208000027333 mucopolysaccharidosis type IIID Diseases 0.000 description 2
- 238000000569 multi-angle light scattering Methods 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 2
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 2
- 210000000869 occipital lobe Anatomy 0.000 description 2
- 210000002475 olfactory pathway Anatomy 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000006920 protein precipitation Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 210000001202 rhombencephalon Anatomy 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 108010010152 sialic acid transport proteins Proteins 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 210000000495 subthalamus Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 210000004785 virchow-robin space Anatomy 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 description 1
- WKSQRQGICJXUAJ-ZMGQZULKSA-N (3S,6R,7S,8R,9R)-3-amino-6,7,8,9,10-pentahydroxy-4,5-dioxodecanoic acid Chemical compound OC(=O)C[C@H](N)C(=O)C(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WKSQRQGICJXUAJ-ZMGQZULKSA-N 0.000 description 1
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- TYIOVYZMKITKRO-UHFFFAOYSA-N 2-[hexadecyl(dimethyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CC([O-])=O TYIOVYZMKITKRO-UHFFFAOYSA-N 0.000 description 1
- FZLJPEPAYPUMMR-RTRLPJTCSA-N 2-acetamido-2-deoxy-D-glucopyranose 1-phosphate Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OP(O)(O)=O FZLJPEPAYPUMMR-RTRLPJTCSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- DIROHOMJLWMERM-UHFFFAOYSA-N 3-[dimethyl(octadecyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O DIROHOMJLWMERM-UHFFFAOYSA-N 0.000 description 1
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
- 229930195730 Aflatoxin Natural products 0.000 description 1
- XWIYFDMXXLINPU-UHFFFAOYSA-N Aflatoxin G Chemical compound O=C1OCCC2=C1C(=O)OC1=C2C(OC)=CC2=C1C1C=COC1O2 XWIYFDMXXLINPU-UHFFFAOYSA-N 0.000 description 1
- 102100031317 Alpha-N-acetylgalactosaminidase Human genes 0.000 description 1
- 102100026277 Alpha-galactosidase A Human genes 0.000 description 1
- 102100031491 Arylsulfatase B Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101710124978 Beta-hexosaminidase B Proteins 0.000 description 1
- 102100032487 Beta-mannosidase Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000017843 C syndrome Diseases 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000005572 Cathepsin A Human genes 0.000 description 1
- 108010059081 Cathepsin A Proteins 0.000 description 1
- 102000004201 Ceramidases Human genes 0.000 description 1
- 108090000751 Ceramidases Proteins 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 101710190709 Eukaryotic translation initiation factor 4 gamma 2 Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 241001076388 Fimbria Species 0.000 description 1
- 208000020916 Gaucher disease type II Diseases 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101100163858 Homo sapiens ARSA gene Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 208000000269 Hyperkinesis Diseases 0.000 description 1
- 206010021033 Hypomenorrhoea Diseases 0.000 description 1
- 108700012441 IGF2 Proteins 0.000 description 1
- 108010053927 Iduronate Sulfatase Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 229920000288 Keratan sulfate Polymers 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000007650 Meningeal Carcinomatosis Diseases 0.000 description 1
- 206010051696 Metastases to meninges Diseases 0.000 description 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
- 206010056893 Mucopolysaccharidosis VII Diseases 0.000 description 1
- 101100400378 Mus musculus Marveld2 gene Proteins 0.000 description 1
- 101100456571 Mus musculus Med12 gene Proteins 0.000 description 1
- 101000822667 Mus musculus Something about silencing protein 10 Proteins 0.000 description 1
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 description 1
- 102100023282 N-acetylglucosamine-6-sulfatase Human genes 0.000 description 1
- 108010023320 N-acetylglucosamine-6-sulfatase Proteins 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 102100027661 N-sulphoglucosamine sulphohydrolase Human genes 0.000 description 1
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- 102000005327 Palmitoyl protein thioesterase Human genes 0.000 description 1
- 108020002591 Palmitoyl protein thioesterase Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 244000294611 Punica granatum Species 0.000 description 1
- 235000014360 Punica granatum Nutrition 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 208000025804 Sanfilippo syndrome type D Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 description 1
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 102100026145 Transitional endoplasmic reticulum ATPase Human genes 0.000 description 1
- 101710132062 Transitional endoplasmic reticulum ATPase Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- LFTYTUAZOPRMMI-CFRASDGPSA-N UDP-N-acetyl-alpha-D-glucosamine Chemical compound O1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](NC(=O)C)[C@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-CFRASDGPSA-N 0.000 description 1
- LFTYTUAZOPRMMI-UHFFFAOYSA-N UNPD164450 Natural products O1C(CO)C(O)C(O)C(NC(=O)C)C1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- LEBBDRXHHNYZIA-LDUWYPJVSA-N [(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] n-[(z)-1,3-dihydroxyoctadec-4-en-2-yl]carbamate Chemical compound CCCCCCCCCCCCC\C=C/C(O)C(CO)NC(=O)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O LEBBDRXHHNYZIA-LDUWYPJVSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 108091006088 activator proteins Proteins 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000005409 aflatoxin Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000007815 allergy Effects 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
- 108010030291 alpha-Galactosidase Proteins 0.000 description 1
- 102000012086 alpha-L-Fucosidase Human genes 0.000 description 1
- 108010061314 alpha-L-Fucosidase Proteins 0.000 description 1
- 108010012864 alpha-Mannosidase Proteins 0.000 description 1
- 102000019199 alpha-Mannosidase Human genes 0.000 description 1
- 108010015684 alpha-N-Acetylgalactosaminidase Proteins 0.000 description 1
- 201000008333 alpha-mannosidosis Diseases 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
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BVGLIYRKPOITBQ-ANPZCEIESA-N benzylpenicillin benzathine Chemical compound C=1C=CC=CC=1C[NH2+]CC[NH2+]CC1=CC=CC=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 BVGLIYRKPOITBQ-ANPZCEIESA-N 0.000 description 1
- WHRVRSCEWKLAHX-LQDWTQKMSA-N benzylpenicillin procaine Chemical compound [H+].CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 WHRVRSCEWKLAHX-LQDWTQKMSA-N 0.000 description 1
- 108010055059 beta-Mannosidase Proteins 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 239000010796 biological waste Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 230000005821 brain abnormality Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 229930183167 cerebroside Natural products 0.000 description 1
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical class Cl* 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
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000000251 cholesterol ester accumulation Effects 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 210000001029 dorsal striatum Anatomy 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000000635 electron micrograph Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 210000000647 epithalamus Anatomy 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 210000004055 fourth ventricle Anatomy 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 150000002254 galactosylceramides Chemical class 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
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 150000002298 globosides Chemical class 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000006207 intravenous dosage form Substances 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000003140 lateral ventricle Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 230000002535 lyotropic effect Effects 0.000 description 1
- 108010045758 lysosomal proteins Proteins 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000001767 medulla oblongata Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 150000003956 methylamines Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000001565 modulated differential scanning calorimetry Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 230000003562 morphometric effect Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000036707 mucopolysaccharidosis type 3C Diseases 0.000 description 1
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 description 1
- 208000012091 mucopolysaccharidosis type IVB Diseases 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- NZXVYLJKFYSEPO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-16-methylheptadecanamide Chemical class CC(C)CCCCCCCCCCCCCCC(=O)NCCCN(C)C NZXVYLJKFYSEPO-UHFFFAOYSA-N 0.000 description 1
- 210000004237 neck muscle Anatomy 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 150000003071 polychlorinated biphenyls Chemical class 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 230000005195 poor health Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000007425 progressive decline Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 238000012950 reanalysis Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 210000000463 red nucleus Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000000211 third ventricle Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/761—Adenovirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/06—Sulfuric ester hydrolases (3.1.6)
- C12Y301/06013—Iduronate-2-sulfatase (3.1.6.13)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01045—Glucosylceramidase (3.2.1.45), i.e. beta-glucocerebrosidase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/0105—Alpha-N-acetylglucosaminidase (3.2.1.50)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35885710P | 2010-06-25 | 2010-06-25 | |
| US61/358,857 | 2010-06-25 | ||
| US36078610P | 2010-07-01 | 2010-07-01 | |
| US61/360,786 | 2010-07-01 | ||
| US38786210P | 2010-09-29 | 2010-09-29 | |
| US61/387,862 | 2010-09-29 | ||
| US201161435710P | 2011-01-24 | 2011-01-24 | |
| US61/435,710 | 2011-01-24 | ||
| US201161442115P | 2011-02-11 | 2011-02-11 | |
| US61/442,115 | 2011-02-11 | ||
| US201161476210P | 2011-04-15 | 2011-04-15 | |
| US61/476,210 | 2011-04-15 | ||
| US201161495268P | 2011-06-09 | 2011-06-09 | |
| US61/495,268 | 2011-06-09 | ||
| PCT/US2011/041924 WO2011163648A1 (en) | 2010-06-25 | 2011-06-25 | Cns delivery of therapeutic agents |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017125281A Division RU2761342C2 (ru) | 2010-06-25 | 2011-06-25 | Доставка терапевтических агентов в цнс |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2012154831A RU2012154831A (ru) | 2014-07-27 |
| RU2626514C2 true RU2626514C2 (ru) | 2017-07-28 |
Family
ID=46888845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012154831A RU2626514C2 (ru) | 2010-06-25 | 2011-06-25 | Доставка к цнс лечебных агентов |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9283181B2 (https=) |
| EP (3) | EP3103469B1 (https=) |
| JP (1) | JP6045491B2 (https=) |
| KR (6) | KR102283671B1 (https=) |
| CN (1) | CN103096918B (https=) |
| AU (4) | AU2011270668B8 (https=) |
| CA (1) | CA2803166C (https=) |
| CY (2) | CY1118265T1 (https=) |
| DK (1) | DK2588130T3 (https=) |
| ES (1) | ES2650689T3 (https=) |
| HR (1) | HRP20161505T1 (https=) |
| IL (3) | IL291554B2 (https=) |
| LT (1) | LT2588130T (https=) |
| MX (1) | MX389903B (https=) |
| NZ (1) | NZ605865A (https=) |
| PE (1) | PE20230169A1 (https=) |
| PL (1) | PL3103469T3 (https=) |
| RU (1) | RU2626514C2 (https=) |
| SM (1) | SMT201600385T1 (https=) |
| UA (1) | UA115648C2 (https=) |
| WO (1) | WO2011163648A1 (https=) |
| ZA (1) | ZA201300671B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2808459C2 (ru) * | 2018-07-12 | 2023-11-28 | Спейскрафт Севен, Ллк | Геннотерапевтические векторы для лечения болезни данона |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057179A2 (en) | 2002-01-11 | 2003-07-17 | Biomarin Pharmaceutical, Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| HRP20191923T1 (hr) | 2010-06-25 | 2020-01-10 | Shire Human Genetic Therapies, Inc. | Postupci i sastavi za isporuku arilsulfataze a u cns |
| KR20230159646A (ko) | 2010-06-25 | 2023-11-21 | 샤이어 휴먼 지네틱 테라피즈 인크. | 이듀로네이트-2-설파타제의 cns 전달을 위한 방법들 및 조성물들 |
| JP6073783B2 (ja) | 2010-06-25 | 2017-02-01 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | ヘパランｎ−スルファターゼのｃｎｓ送達のための方法および組成物 |
| PT3103469T (pt) | 2010-06-25 | 2021-03-04 | Shire Human Genetic Therapies | Administração de agentes terapêuticos no snc |
| LT2588130T (lt) | 2010-06-25 | 2016-12-12 | Shire Human Genetic Therapies, Inc. | Terapinės priemonės pristatymas cns |
| WO2012101671A1 (en) * | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
| CN103747807B (zh) | 2011-07-05 | 2016-12-07 | 比奥阿赛斯技术有限公司 | P97‑抗体缀合物和使用方法 |
| SG10201510106PA (en) * | 2011-10-12 | 2016-01-28 | Synageva Biopharma Corp | Recombinant human naglu protein and uses thereof |
| US9682129B2 (en) | 2011-12-23 | 2017-06-20 | Shire Human Genetic Therapies, Inc. | Treatment of cognitive impairment of hunter syndrome by intrathecal delivery of iduronate-2-sulfatase |
| US20140377244A1 (en) | 2011-12-23 | 2014-12-25 | Shire Human Genetic Therapies, Inc. | Stable formulations for cns delivery of arylsulfatase a |
| CA3140358A1 (en) * | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| CN112126634A (zh) | 2013-01-09 | 2020-12-25 | 夏尔人类遗传性治疗公司 | 含用于纯化芳基硫酸酯酶a的方法 |
| AU2014218854B2 (en) | 2013-02-20 | 2019-01-24 | Valerion Therapeutics, Llc | Methods and compositions for treatment of Pompe disease |
| AU2014243816B2 (en) | 2013-03-13 | 2019-01-31 | Bioasis Technologies Inc. | Fragments of p97 and uses thereof |
| CN115120746A (zh) * | 2013-05-15 | 2022-09-30 | 明尼苏达大学董事会 | 腺相关病毒介导的基因向中枢神经系统转移 |
| JP6603227B2 (ja) | 2014-02-03 | 2019-11-06 | バイオアシス テクノロジーズ インコーポレイテッド | Ｐ９７融合タンパク質 |
| DK3107562T3 (da) | 2014-02-19 | 2019-12-16 | Bioasis Technologies Inc | P97-ids-fusionsproteiner |
| AU2015252906C1 (en) | 2014-05-01 | 2020-09-17 | Bioasis Technologies Inc. | p97-polynucleotide conjugates |
| EP3185889B1 (en) * | 2014-08-11 | 2020-07-15 | Shire Human Genetic Therapies, Inc. | Mannose-6-phosphate bearing peptides fused to lysosomal enzymes |
| EP3200816A1 (en) | 2014-09-29 | 2017-08-09 | Alexion Pharmaceuticals, Inc. | Methods of treating mucopolysaccharidosis iiib (mpsiiib) |
| WO2016100591A1 (en) * | 2014-12-19 | 2016-06-23 | Biogen Ma Inc. | Apparatus for compound dispersion |
| CA2985235A1 (en) | 2015-05-07 | 2016-11-10 | Shire Human Genetic Therapies, Inc. | Glucocerebrosidase gene therapy for parkinson's disease |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| KR20170004814A (ko) * | 2015-07-02 | 2017-01-11 | 주식회사 녹십자 | 헌터증후군 치료제 |
| WO2017062666A2 (en) * | 2015-10-06 | 2017-04-13 | Patricia Dickson | Enzyme replacement therapy for mucopolysaccharidosis iiid |
| US10123969B2 (en) | 2015-10-15 | 2018-11-13 | Wisconsin Alumni Research Foundation | Osmotic enhancement of drug/therapeutic delivery to the brain following infusion or injection into the cerebrospinal fluid |
| MX2018007330A (es) * | 2015-12-15 | 2019-03-14 | Genzyme Corp | Vectores virales adeno-asociados para tratar mucolipidosis de tipo ii. |
| PL3397270T3 (pl) * | 2015-12-30 | 2024-08-19 | Green Cross Corporation | Kompozycje do zastosowania w leczeniu zespołu huntera |
| JP2019509270A (ja) * | 2016-02-17 | 2019-04-04 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | アリールスルファターゼａのｃｎｓ送達のための方法および組成物 |
| SG10201912761UA (en) | 2016-04-15 | 2020-02-27 | The Trustees Of The Univ Of Pennsyvania | Gene therapy for treating mucopolysaccharidosis type ii |
| US11957713B2 (en) | 2016-10-14 | 2024-04-16 | Children's Medical Center Corporation | Compositions and methods for treating diseases and disorders of the central nervous system |
| CA3050690A1 (en) | 2017-01-17 | 2018-07-26 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for diagnosing and treating peroxisomal diseases |
| GB201709459D0 (en) | 2017-06-14 | 2017-07-26 | Intrabio Ltd | Treatment for migraine |
| CN111278453A (zh) * | 2017-09-07 | 2020-06-12 | Jcr制药股份有限公司 | 水性药物组合物 |
| KR102883778B1 (ko) | 2017-09-22 | 2025-11-12 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | Ii형 점액다당류증의 치료를 위한 유전자 요법 |
| CR20200129A (es) | 2017-10-02 | 2020-08-22 | Denali Therapeutics Inc | Proteínas de fusión que comprenden enzimas de terapia de reemplazo de enzimas |
| US12458614B2 (en) | 2017-10-18 | 2025-11-04 | Intrabio Ltd | Therapeutic agents for improved mobility and cognitive function and for treating neurodegenerative diseases and lysosomal storage disorders |
| IL273929B2 (en) | 2017-10-18 | 2024-11-01 | Intrabio Ltd | Therapeutic agents for neurodegenerative diseases |
| CN111699249A (zh) | 2017-12-19 | 2020-09-22 | 夏尔人类遗传性治疗公司 | 纯化的芳基硫酸酯酶a及其组合物 |
| MA51836B1 (fr) | 2018-02-15 | 2025-01-31 | Intrabio Ltd | Agents thérapeutiques permettant de traiter le syndrome des jambes sans repos |
| US11738068B2 (en) | 2018-06-25 | 2023-08-29 | Jcr Pharmaceuticals Co., Ltd. | Protein-containing aqueous liquid formulation |
| SMT202400334T1 (it) | 2019-03-02 | 2024-09-16 | Intrabio Ltd | (n-)acetil-l-leucina per il trattamento di lesioni cerebrali traumatiche |
| RS67283B1 (sr) | 2019-06-28 | 2025-11-28 | Intrabio Ltd | Kombinovana terapija sa acetil-leucinom i miglustatom za lečenje bolesti lizozomskog skladištenja |
| PT4021575T (pt) * | 2019-08-29 | 2024-07-30 | Biomarin Pharm Inc | Métodos para o tratamento da doença cln2 em sujeitos pediátricos |
| WO2021144720A1 (en) | 2020-01-13 | 2021-07-22 | Intrabio Ltd | Treatment of late-onset neurodegenerative diseases in heterozygous npc1 gene mutation carriers |
| US20230201150A1 (en) | 2020-05-22 | 2023-06-29 | Intrabio Ltd. | The combination of acetyl leucine and 4-aminopyridine or acetazolamide for treating ataxia |
| WO2024102808A2 (en) * | 2022-11-09 | 2024-05-16 | Gmp Biotechnology Limited | Compositions and methods for cns diseases |
| WO2024176112A1 (en) | 2023-02-21 | 2024-08-29 | Takeda Pharmaceutical Company Limited | Large scale production of recombinant arylsulfatase a and compositions thereof |
| WO2025264957A2 (en) | 2024-06-20 | 2025-12-26 | Intrabio Inc. | Acetyl leucine for treating neurodevelopmental disorders |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005089462A2 (en) * | 2004-03-18 | 2005-09-29 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
| US20060177433A1 (en) * | 2002-04-25 | 2006-08-10 | Treco Douglas A | Treatment of alpha-galactosidase a deficiency |
| US20090017005A1 (en) * | 2003-08-29 | 2009-01-15 | Biomarion Pharmaceutical Inc. | Delivery of Therapeutic Compounds to the Brain and Other Tissues |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4743265A (en) | 1986-04-23 | 1988-05-10 | Dij Catheter Corp | Articulated catheter placement device |
| US5863782A (en) | 1995-04-19 | 1999-01-26 | Women's And Children's Hospital | Synthetic mammalian sulphamidase and genetic sequences encoding same |
| US6118045A (en) | 1995-08-02 | 2000-09-12 | Pharming B.V. | Lysosomal proteins produced in the milk of transgenic animals |
| US6063378A (en) | 1997-08-22 | 2000-05-16 | Seikagaku Corporation | Therapeutic agent for herniated intervertebral disc |
| ES2312222T3 (es) | 1998-12-07 | 2009-02-16 | Genzyme Corporation | Tratamiento de la enfermedad de pompe. |
| US6217552B1 (en) | 1999-03-01 | 2001-04-17 | Coaxia, Inc. | Medical device for selective intrathecal spinal cooling in aortic surgery and spinal trauma |
| US20020052311A1 (en) | 1999-09-03 | 2002-05-02 | Beka Solomon | Methods and compostions for the treatment and/or diagnosis of neurological diseases and disorders |
| US6534300B1 (en) | 1999-09-14 | 2003-03-18 | Genzyme Glycobiology Research Institute, Inc. | Methods for producing highly phosphorylated lysosomal hydrolases |
| US20020099025A1 (en) * | 1999-12-30 | 2002-07-25 | Heywood James A. | Treatment of neurological disorders |
| WO2002087510A2 (en) | 2001-04-30 | 2002-11-07 | Symbiontics, Inc. | Subcellular targeting of therapeutic proteins |
| US7629309B2 (en) | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20040005309A1 (en) | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20030072761A1 (en) | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| AU2002347910A1 (en) | 2001-10-16 | 2003-04-28 | Symbiontics Inc. | Methods and compositions for targeting proteins across the blood brain barrier |
| EP1514106A4 (en) | 2002-05-29 | 2007-05-09 | Zystor Therapeutics Inc | TARGETED THERAPEUTIC PROTEINS |
| ES2371913T3 (es) | 2003-01-22 | 2012-01-11 | Duke University | Constructos mejorados para expresar polipéptidos lisosomales. |
| EP1638605B1 (en) | 2003-06-20 | 2014-01-08 | Raptor Pharmaceutical, Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| US20050026823A1 (en) * | 2003-06-20 | 2005-02-03 | Biomarin Pharmaceutical Inc. | Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues |
| EP1713904B1 (en) | 2004-01-30 | 2016-06-29 | Shire Pharmaceuticals Ireland Limited | Production and purification of recombinant arylsulfatase a |
| WO2005074888A2 (en) | 2004-02-03 | 2005-08-18 | Biodelivery Sciences International, Inc. | Replacement enzyme cochleates |
| US20080014188A1 (en) | 2004-02-06 | 2008-01-17 | Zankel Todd C | Manufacture of Highly Phosphorylated Lysosomal Enzymes and Uses Thereof |
| CA2553955C (en) | 2004-02-10 | 2012-08-28 | Zystor Therapeutics, Inc. | Acid alpha-glucosidase and fragments thereof |
| US20090297592A1 (en) | 2005-05-11 | 2009-12-03 | Jcr Pharmaceuticals Co., Ltd. | Lipid Vesicle Composition |
| AU2006254796B2 (en) | 2005-06-08 | 2012-08-16 | Amicus Therapeutics, Inc. | Treatment of CNS disorders associated with mutations in genes encoding lysosomal enzymes |
| AR059089A1 (es) * | 2006-01-20 | 2008-03-12 | Genzyme Corp | Administracion intraventricular de una enzima para enfermedades de almacenamiento lisosomal |
| HUE042402T2 (hu) * | 2006-04-04 | 2019-06-28 | Chiesi Farm Spa | Eljárás polipeptid töményítésére |
| GB0611463D0 (en) | 2006-06-09 | 2006-07-19 | Novartis Ag | Organic compounds |
| WO2008070769A1 (en) | 2006-12-06 | 2008-06-12 | Medtronic, Inc. | Intrathecal catheter |
| CA2680189A1 (en) | 2007-03-06 | 2008-09-12 | Saint Louis University | Modified enzyme and treatment method |
| US20110059508A1 (en) * | 2007-06-29 | 2011-03-10 | National University Corporation Nagoya University | Improving agent for dysfunction due to neuropathy and rho kinase activation inhibitor |
| WO2009017005A1 (ja) | 2007-07-27 | 2009-02-05 | Sharp Kabushiki Kaisha | 移動局装置、基地局装置、通信システム及びプログラム |
| JP2010536341A (ja) | 2007-08-15 | 2010-12-02 | アムニクス， インコーポレイテッド | 生物学的に活性なポリペプチドの特性を改変するための組成物および方法 |
| US8420081B2 (en) | 2007-11-30 | 2013-04-16 | Abbvie, Inc. | Antibody formulations and methods of making same |
| US7722865B2 (en) | 2008-01-18 | 2010-05-25 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
| JP5627571B2 (ja) | 2008-05-07 | 2014-11-19 | バイオマリン ファーマシューティカル インコーポレイテッド | リソソーム標的化ペプチドおよびその使用 |
| US8436489B2 (en) | 2009-06-29 | 2013-05-07 | Lightsail Energy, Inc. | Compressed air energy storage system utilizing two-phase flow to facilitate heat exchange |
| US20110318324A1 (en) | 2010-06-25 | 2011-12-29 | Shire Human Genetic Therapies, Inc. | Methods and compositions for cns delivery of b-galactocerebrosidase |
| JP6073783B2 (ja) | 2010-06-25 | 2017-02-01 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | ヘパランｎ−スルファターゼのｃｎｓ送達のための方法および組成物 |
| HRP20191923T1 (hr) | 2010-06-25 | 2020-01-10 | Shire Human Genetic Therapies, Inc. | Postupci i sastavi za isporuku arilsulfataze a u cns |
| LT2588130T (lt) | 2010-06-25 | 2016-12-12 | Shire Human Genetic Therapies, Inc. | Terapinės priemonės pristatymas cns |
| AU2011270672B2 (en) | 2010-06-25 | 2017-01-12 | Shire Human Genetic Therapies, Inc. | Treatment of Sanfilippo Syndrome type B |
| KR20230159646A (ko) * | 2010-06-25 | 2023-11-21 | 샤이어 휴먼 지네틱 테라피즈 인크. | 이듀로네이트-2-설파타제의 cns 전달을 위한 방법들 및 조성물들 |
| PT3103469T (pt) | 2010-06-25 | 2021-03-04 | Shire Human Genetic Therapies | Administração de agentes terapêuticos no snc |
| JP2012062312A (ja) | 2010-08-19 | 2012-03-29 | Yoshikatsu Eto | ハンター症候群の治療剤 |
-
2011
- 2011-06-25 LT LTEP11799035.8T patent/LT2588130T/lt unknown
- 2011-06-25 MX MX2018003131A patent/MX389903B/es unknown
- 2011-06-25 KR KR1020217003036A patent/KR102283671B1/ko active Active
- 2011-06-25 ES ES11799035T patent/ES2650689T3/es active Active
- 2011-06-25 WO PCT/US2011/041924 patent/WO2011163648A1/en not_active Ceased
- 2011-06-25 NZ NZ605865A patent/NZ605865A/en unknown
- 2011-06-25 JP JP2013516844A patent/JP6045491B2/ja active Active
- 2011-06-25 AU AU2011270668A patent/AU2011270668B8/en active Active
- 2011-06-25 IL IL291554A patent/IL291554B2/en unknown
- 2011-06-25 HR HRP20161505TT patent/HRP20161505T1/hr unknown
- 2011-06-25 KR KR1020247014519A patent/KR20240068752A/ko not_active Withdrawn
- 2011-06-25 EP EP16179150.4A patent/EP3103469B1/en not_active Revoked
- 2011-06-25 EP EP11799035.8A patent/EP2588130B1/en active Active
- 2011-06-25 PE PE2022001782A patent/PE20230169A1/es unknown
- 2011-06-25 CN CN201180040978.5A patent/CN103096918B/zh active Active
- 2011-06-25 KR KR1020197022037A patent/KR102211960B1/ko active Active
- 2011-06-25 SM SM20160385T patent/SMT201600385T1/it unknown
- 2011-06-25 DK DK11799035.8T patent/DK2588130T3/en active
- 2011-06-25 KR KR1020217042861A patent/KR102663407B1/ko active Active
- 2011-06-25 PL PL16179150T patent/PL3103469T3/pl unknown
- 2011-06-25 CA CA2803166A patent/CA2803166C/en active Active
- 2011-06-25 EP EP20212573.8A patent/EP3875107A1/en active Pending
- 2011-06-25 US US13/168,961 patent/US9283181B2/en active Active
- 2011-06-25 RU RU2012154831A patent/RU2626514C2/ru active
- 2011-06-25 UA UAA201214666A patent/UA115648C2/uk unknown
- 2011-06-25 KR KR1020137001748A patent/KR102007044B1/ko active Active
- 2011-06-25 KR KR1020217023503A patent/KR102345973B1/ko active Active
-
2012
- 2012-12-18 IL IL223717A patent/IL223717B/en active IP Right Grant
-
2013
- 2013-01-25 ZA ZA2013/00671A patent/ZA201300671B/en unknown
-
2016
- 2016-11-17 CY CY20161101188T patent/CY1118265T1/el unknown
-
2017
- 2017-04-10 AU AU2017202349A patent/AU2017202349B2/en active Active
-
2019
- 2019-06-11 AU AU2019204056A patent/AU2019204056B2/en active Active
-
2020
- 2020-04-07 IL IL273889A patent/IL273889B/en unknown
-
2021
- 2021-03-08 CY CY20211100195T patent/CY1124154T1/el unknown
- 2021-10-20 AU AU2021254564A patent/AU2021254564B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060177433A1 (en) * | 2002-04-25 | 2006-08-10 | Treco Douglas A | Treatment of alpha-galactosidase a deficiency |
| US20090017005A1 (en) * | 2003-08-29 | 2009-01-15 | Biomarion Pharmaceutical Inc. | Delivery of Therapeutic Compounds to the Brain and Other Tissues |
| WO2005089462A2 (en) * | 2004-03-18 | 2005-09-29 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
Non-Patent Citations (2)
| Title |
|---|
| LEE W. C. et al., Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy, The FASEB Journal, August, 2007,vol. 21 no. 10, рр. 2520-2527. Найдено из Интернета на сайте http://www.fasebj.org/content/21/10/2520.full.pdf+html. WATSON G. et al., Intrathecal administration of AAV vectors for the treatment of lysosomal storage in the brains of MPS I mice, Gene Ther. 2006 Jun;13(11):917-25-, с.917 Найдено из Интернета на сайте http://www.nature.com/gt/journal/v13/n11/pdf/3302735a.pdf. * |
| LEE W. C. et al., Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy, The FASEB Journal, August, 2007,vol. 21 no. 10, рр. 2520-2527. Найдено из Интернета на сайте http://www.fasebj.org/content/21/10/2520.full.pdf+html. WATSON G. et al., Intrathecal administration of AAV vectors for the treatment of lysosomal storage in the brains of MPS I mice, Gene Ther. 2006 Jun;13(11):917-25-реферат, с.917 Найдено из Интернета на сайте http://www.nature.com/gt/journal/v13/n11/pdf/3302735a.pdf. * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2830306C2 (ru) * | 2017-12-19 | 2024-11-18 | Такеда Фармасьютикал Компани Лимитед | Очищенная арилсульфатаза a и композиции на ее основе |
| RU2808459C2 (ru) * | 2018-07-12 | 2023-11-28 | Спейскрафт Севен, Ллк | Геннотерапевтические векторы для лечения болезни данона |
| RU2858472C2 (ru) * | 2020-12-07 | 2026-03-17 | Спейскрафт Севен, Ллк | Способ лечения болезни Данона |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2626514C2 (ru) | Доставка к цнс лечебных агентов | |
| US12409210B2 (en) | CNS delivery of therapeutic agents | |
| RU2671503C2 (ru) | Способы и композиции для доставки в цнс арилсульфатазы а | |
| BR112012033205A2 (pt) | uso de uma composição compreendendo agentes terapêuticos para liberação ao sistema nervoso central | |
| HK1218719B (zh) | 治疗试剂的cns递送 | |
| HK1230954A1 (en) | Cns delivery of therapeutic agents | |
| HK1184712B (en) | Cns delivery of therapeutic agents | |
| HK1230954B (en) | Cns delivery of therapeutic agents |