AU2007253212B2 - Use of proinsulin for the preparation of a neuroprotective pharmaceutical composition, therapeutic composition containing it and applications thereof - Google Patents
Use of proinsulin for the preparation of a neuroprotective pharmaceutical composition, therapeutic composition containing it and applications thereof Download PDFInfo
- Publication number
- AU2007253212B2 AU2007253212B2 AU2007253212A AU2007253212A AU2007253212B2 AU 2007253212 B2 AU2007253212 B2 AU 2007253212B2 AU 2007253212 A AU2007253212 A AU 2007253212A AU 2007253212 A AU2007253212 A AU 2007253212A AU 2007253212 B2 AU2007253212 B2 AU 2007253212B2
- Authority
- AU
- Australia
- Prior art keywords
- proinsulin
- nucleotide sequence
- sequence
- human
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 108010076181 Proinsulin Proteins 0.000 title claims abstract description 193
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 230000000324 neuroprotective effect Effects 0.000 title claims description 20
- 239000000203 mixture Substances 0.000 title claims description 14
- 230000001225 therapeutic effect Effects 0.000 title claims description 11
- 241000282414 Homo sapiens Species 0.000 claims abstract description 100
- 239000002773 nucleotide Substances 0.000 claims abstract description 78
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 77
- 150000001875 compounds Chemical class 0.000 claims abstract description 57
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 47
- 230000000694 effects Effects 0.000 claims abstract description 46
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 26
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 12
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 12
- 208000035475 disorder Diseases 0.000 claims abstract description 10
- 230000007170 pathology Effects 0.000 claims abstract description 10
- 238000003782 apoptosis assay Methods 0.000 claims abstract description 9
- 230000005522 programmed cell death Effects 0.000 claims abstract description 9
- 229940126601 medicinal product Drugs 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 31
- 230000004770 neurodegeneration Effects 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 27
- 239000013604 expression vector Substances 0.000 claims description 23
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 19
- 239000000411 inducer Substances 0.000 claims description 15
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 14
- 239000012634 fragment Substances 0.000 claims description 13
- 230000002068 genetic effect Effects 0.000 claims description 13
- 210000003205 muscle Anatomy 0.000 claims description 13
- 210000001519 tissue Anatomy 0.000 claims description 13
- 230000002459 sustained effect Effects 0.000 claims description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 11
- 210000005260 human cell Anatomy 0.000 claims description 8
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 6
- 230000004112 neuroprotection Effects 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 201000002832 Lewy body dementia Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 230000009885 systemic effect Effects 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 10
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 5
- 239000012190 activator Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 91
- 210000001525 retina Anatomy 0.000 description 34
- 150000001413 amino acids Chemical group 0.000 description 32
- 230000004044 response Effects 0.000 description 31
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 26
- 108091008695 photoreceptors Proteins 0.000 description 26
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 230000007850 degeneration Effects 0.000 description 22
- 230000002207 retinal effect Effects 0.000 description 22
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 102000004877 Insulin Human genes 0.000 description 15
- 108090001061 Insulin Proteins 0.000 description 15
- 230000034994 death Effects 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 230000009261 transgenic effect Effects 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 230000030833 cell death Effects 0.000 description 13
- 229940125396 insulin Drugs 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 201000007737 Retinal degeneration Diseases 0.000 description 12
- 210000002569 neuron Anatomy 0.000 description 12
- 230000004258 retinal degeneration Effects 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- 230000000946 synaptic effect Effects 0.000 description 11
- 238000011830 transgenic mouse model Methods 0.000 description 11
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 10
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000007929 subcutaneous injection Substances 0.000 description 10
- 238000010254 subcutaneous injection Methods 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 230000004382 visual function Effects 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000016349 Myosin Light Chains Human genes 0.000 description 7
- 108010067385 Myosin Light Chains Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 230000006978 adaptation Effects 0.000 description 7
- 230000004075 alteration Effects 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 238000002372 labelling Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 6
- 230000004438 eyesight Effects 0.000 description 6
- 210000004940 nucleus Anatomy 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000002571 electroretinography Methods 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 210000005157 neural retina Anatomy 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 208000003098 Ganglion Cysts Diseases 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 208000005400 Synovial Cyst Diseases 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 230000001640 apoptogenic effect Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 210000000653 nervous system Anatomy 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 230000007542 postnatal development Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 210000003699 striated muscle Anatomy 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 3
- 101710186708 Agglutinin Proteins 0.000 description 3
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 3
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 101710146024 Horcolin Proteins 0.000 description 3
- 101710189395 Lectin Proteins 0.000 description 3
- 101710179758 Mannose-specific lectin Proteins 0.000 description 3
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 3
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 3
- 102000004330 Rhodopsin Human genes 0.000 description 3
- 108090000820 Rhodopsin Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009692 acute damage Effects 0.000 description 3
- 239000000910 agglutinin Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000003412 degenerative effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000003205 genotyping method Methods 0.000 description 3
- 230000002518 glial effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 108010066381 preproinsulin Proteins 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 239000013603 viral vector Substances 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
- 244000025254 Cannabis sativa Species 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102000004590 Peripherins Human genes 0.000 description 2
- 108010003081 Peripherins Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000001153 interneuron Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000012120 mounting media Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 238000012758 nuclear staining Methods 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 210000005047 peripherin Anatomy 0.000 description 2
- 230000008823 permeabilization Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000000608 photoreceptor cell Anatomy 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000751 protein extraction Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000003994 retinal ganglion cell Anatomy 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 210000002504 synaptic vesicle Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- 101150072531 10 gene Proteins 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 208000036443 AIPL1-related retinopathy Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101150030072 CNTF gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010019899 Hereditary retinal dystrophy Diseases 0.000 description 1
- 101000731000 Homo sapiens Membrane-associated progesterone receptor component 1 Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100032399 Membrane-associated progesterone receptor component 1 Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 241000275031 Nica Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108010037638 Type 6 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000006726 chronic neurodegeneration Effects 0.000 description 1
- 201000006754 cone-rod dystrophy Diseases 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000027832 depurination Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000011977 dual antiplatelet therapy Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 208000010522 hyperproinsulinemia Diseases 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 230000004301 light adaptation Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000004297 night vision Effects 0.000 description 1
- 230000004987 nonapoptotic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108010005636 polypeptide C Proteins 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 210000003314 quadriceps muscle Anatomy 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000020129 regulation of cell death Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000004243 retinal function Effects 0.000 description 1
- 230000004500 retinal neurogenesis Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 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
- 239000007787 solid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200601314A ES2331342B1 (es) | 2006-05-22 | 2006-05-22 | Uso de la proinsulina para la elaboracion de una composicion farmaceutica neuroprotectora, composicion terapeutica que la contiene y sus aplicaciones. |
| ESP200601314 | 2006-05-22 | ||
| PCT/ES2007/070097 WO2007135220A1 (es) | 2006-05-22 | 2007-05-21 | Uso de la proinsulina para la elaboración de una composición farmacéutica neuroprotectora, composición terapéutica que la contiene y sus aplicaciones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2007253212A1 AU2007253212A1 (en) | 2007-11-29 |
| AU2007253212B2 true AU2007253212B2 (en) | 2012-09-27 |
Family
ID=38722988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007253212A Ceased AU2007253212B2 (en) | 2006-05-22 | 2007-05-21 | Use of proinsulin for the preparation of a neuroprotective pharmaceutical composition, therapeutic composition containing it and applications thereof |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20100330042A1 (enExample) |
| EP (1) | EP2042189B1 (enExample) |
| JP (1) | JP4727748B2 (enExample) |
| AU (1) | AU2007253212B2 (enExample) |
| CA (1) | CA2652983C (enExample) |
| ES (2) | ES2331342B1 (enExample) |
| WO (1) | WO2007135220A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110021974A1 (en) * | 2010-10-05 | 2011-01-27 | Shantha Totada R | Retinitis pigmentosa treatment and prophalaxis |
| JP6199965B2 (ja) * | 2012-07-11 | 2017-09-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | Rpgrx連鎖性網膜変性のaav媒介型遺伝子治療 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2104380A (en) * | 1981-08-27 | 1983-03-09 | Lilly Co Eli | Human proinsulin pharmaceutical formulations |
| WO2000004171A1 (en) * | 1998-07-15 | 2000-01-27 | Wisconsin Alumni Research Foundation | Treatment of diabetes with synthetic beta cells |
| US20030220229A1 (en) * | 1994-07-08 | 2003-11-27 | Trustees Of Dartmouth College | Proinsulin peptide compounds for detecting and treating type I diabetes |
| US20040053817A1 (en) * | 2000-11-08 | 2004-03-18 | Detlef Mohr | Delayed-release pharmaceutical formulations |
| WO2004083234A2 (en) * | 2003-03-14 | 2004-09-30 | Nobex Corporation | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5652214A (en) * | 1989-06-05 | 1997-07-29 | Cephalon, Inc. | Treating disorders by application of insulin-like growth factors and analogs |
| US5667968A (en) * | 1989-08-30 | 1997-09-16 | Regeneron Pharmaceuticals, Inc. | Prevention of retinal injury and degeneration by specific factors |
| WO2003103608A2 (en) * | 2002-06-11 | 2003-12-18 | The Burnham Institute | Neuroprotective synergy of erythropoietin and insulin-like growth factor |
-
2006
- 2006-05-22 ES ES200601314A patent/ES2331342B1/es not_active Expired - Fee Related
-
2007
- 2007-05-21 AU AU2007253212A patent/AU2007253212B2/en not_active Ceased
- 2007-05-21 JP JP2009511534A patent/JP4727748B2/ja not_active Expired - Fee Related
- 2007-05-21 CA CA2652983A patent/CA2652983C/en not_active Expired - Fee Related
- 2007-05-21 US US12/227,554 patent/US20100330042A1/en not_active Abandoned
- 2007-05-21 ES ES07765882T patent/ES2433389T3/es active Active
- 2007-05-21 WO PCT/ES2007/070097 patent/WO2007135220A1/es not_active Ceased
- 2007-05-21 EP EP07765882.1A patent/EP2042189B1/en not_active Not-in-force
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2104380A (en) * | 1981-08-27 | 1983-03-09 | Lilly Co Eli | Human proinsulin pharmaceutical formulations |
| US20030220229A1 (en) * | 1994-07-08 | 2003-11-27 | Trustees Of Dartmouth College | Proinsulin peptide compounds for detecting and treating type I diabetes |
| WO2000004171A1 (en) * | 1998-07-15 | 2000-01-27 | Wisconsin Alumni Research Foundation | Treatment of diabetes with synthetic beta cells |
| US20040053817A1 (en) * | 2000-11-08 | 2004-03-18 | Detlef Mohr | Delayed-release pharmaceutical formulations |
| WO2004083234A2 (en) * | 2003-03-14 | 2004-09-30 | Nobex Corporation | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
Non-Patent Citations (2)
| Title |
|---|
| Diaz, B. et al. 1999 Euro. J. Neurosci. vol. 11, pp. 1624-1632 * |
| Diaz, B. et al. 2000 Develop. vol. 127, pp. 1641-1649 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2433389T3 (es) | 2013-12-10 |
| EP2042189B1 (en) | 2013-06-26 |
| WO2007135220A1 (es) | 2007-11-29 |
| JP4727748B2 (ja) | 2011-07-20 |
| US20100330042A1 (en) | 2010-12-30 |
| CA2652983A1 (en) | 2007-11-29 |
| AU2007253212A1 (en) | 2007-11-29 |
| CA2652983C (en) | 2016-07-19 |
| ES2331342B1 (es) | 2010-10-13 |
| EP2042189A4 (en) | 2010-02-17 |
| JP2009537612A (ja) | 2009-10-29 |
| ES2331342A1 (es) | 2009-12-29 |
| EP2042189A1 (en) | 2009-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kobayashi et al. | HRG4 (UNC119) mutation found in cone–rod dystrophy causes retinal degeneration in a transgenic model | |
| Petters et al. | Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa | |
| Pang et al. | AAV-mediated gene therapy for retinal degeneration in the rd10 mouse containing a recessive PDEβ mutation | |
| Matsuo et al. | Mouse Otx2 functions in the formation and patterning of rostral head. | |
| US6204251B1 (en) | Ocular gene therapy | |
| JP6827320B2 (ja) | LCA−8及び進行性RPを治療するための組換えAAV−Crumbsホモログ組成物及び方法 | |
| Hu et al. | In vivo CRISPR/Cas9-mediated genome editing mitigates photoreceptor degeneration in a mouse model of X-linked retinitis pigmentosa | |
| Shiels | TRPM3_miR-204: a complex locus for eye development and disease | |
| US20070264244A1 (en) | Pigment epithelial cell of the eye, its production and use in therapy of an eye or CNS disease | |
| WO1996013276A9 (en) | Ocular gene therapy | |
| RU2251838C2 (ru) | Способ получения неприродной трансгенной мыши с дефицитом гена рецептора 2 кортиколиберина и ее использование | |
| Jones et al. | Retinal expression of γ-crystallins in the mouse | |
| Palmer et al. | Expression of Gtf2ird1, the Williams syndrome-associated gene, during mouse development | |
| Stieger et al. | Adeno-associated virus mediated gene therapy for retinal degenerative diseases | |
| US11351225B2 (en) | Methods for modulating development and function of photoreceptor cells | |
| AU2007253212B2 (en) | Use of proinsulin for the preparation of a neuroprotective pharmaceutical composition, therapeutic composition containing it and applications thereof | |
| EP1360898A1 (en) | Joint utilization of the insulin gene and the glucokinase gene in the development of therapeutic approaches for diabetes mellitus | |
| JP2002087983A (ja) | 筋萎縮性側索硬化症治療剤 | |
| Shigesada et al. | Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration | |
| Yokoyama et al. | Genomic structure and functional characterization of NBPhox (PMX2B), a homeodomain protein specific to catecholaminergic cells that is involved in second messenger-mediated transcriptional activation | |
| CN110755427A (zh) | 一种治疗视网膜退行性疾病的药物 | |
| JP2023038873A (ja) | 遺伝子改変型ゼブラフィッシュ | |
| WO1998015628A1 (fr) | Nouveau gene de semaphorine: la semaphorine w | |
| WO2005023311A2 (en) | Novel targets for the treatment of retina diseases | |
| CN113956345A (zh) | Angpt4蛋白及其编码基因在调控心脏损伤后的修复与再生能力中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |