ES2986807T3 - Pridopidina para su uso en el tratamiento del síndrome de Rett - Google Patents
Pridopidina para su uso en el tratamiento del síndrome de Rett Download PDFInfo
- Publication number
- ES2986807T3 ES2986807T3 ES22150695T ES22150695T ES2986807T3 ES 2986807 T3 ES2986807 T3 ES 2986807T3 ES 22150695 T ES22150695 T ES 22150695T ES 22150695 T ES22150695 T ES 22150695T ES 2986807 T3 ES2986807 T3 ES 2986807T3
- Authority
- ES
- Spain
- Prior art keywords
- pridopidine
- administered
- composition
- mice
- subject
- 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.)
- Active
Links
- YGKUEOZJFIXDGI-UHFFFAOYSA-N pridopidine Chemical compound C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGKUEOZJFIXDGI-UHFFFAOYSA-N 0.000 title claims abstract description 179
- 229950003764 pridopidine Drugs 0.000 title claims abstract description 177
- 208000006289 Rett Syndrome Diseases 0.000 title claims abstract description 54
- 238000011282 treatment Methods 0.000 title abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 208000024891 symptom Diseases 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 208000014825 Abnormal muscle tone Diseases 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 208000010428 Muscle Weakness Diseases 0.000 claims description 6
- 206010028372 Muscular weakness Diseases 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- -1 aconate Chemical compound 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 229910002651 NO3 Inorganic materials 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 3
- 229940072107 ascorbate Drugs 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 3
- 229940077388 benzenesulfonate Drugs 0.000 claims description 3
- 229940050390 benzoate Drugs 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 229940114081 cinnamate Drugs 0.000 claims description 3
- 229940001468 citrate Drugs 0.000 claims description 3
- 229950005627 embonate Drugs 0.000 claims description 3
- 229930195712 glutamate Natural products 0.000 claims description 3
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 238000007913 intrathecal administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 3
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 3
- 229960001860 salicylate Drugs 0.000 claims description 3
- 229940075554 sorbate Drugs 0.000 claims description 3
- 229940114926 stearate Drugs 0.000 claims description 3
- 238000010254 subcutaneous injection Methods 0.000 claims description 3
- 239000007929 subcutaneous injection Substances 0.000 claims description 3
- 229940086735 succinate Drugs 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 description 70
- 239000003981 vehicle Substances 0.000 description 47
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 36
- 102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 35
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 32
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 32
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 32
- 230000000694 effects Effects 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 238000012360 testing method Methods 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 20
- 230000005021 gait Effects 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 210000004556 brain Anatomy 0.000 description 17
- 108020004999 messenger RNA Proteins 0.000 description 17
- 239000000523 sample Substances 0.000 description 15
- 238000011084 recovery Methods 0.000 description 13
- 108700039887 Essential Genes Proteins 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 11
- 230000001934 delay Effects 0.000 description 11
- 229910052805 deuterium Inorganic materials 0.000 description 11
- 201000010099 disease Diseases 0.000 description 9
- 230000006977 prepulse inhibition Effects 0.000 description 9
- 230000024188 startle response Effects 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 238000003753 real-time PCR Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 6
- 230000037230 mobility Effects 0.000 description 6
- 230000036278 prepulse Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 230000003542 behavioural effect Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 230000000737 periodic effect Effects 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- YGRHOYQMBLLGEV-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-propylpiperidine;hydrochloride Chemical compound Cl.C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGRHOYQMBLLGEV-UHFFFAOYSA-N 0.000 description 4
- 102100020871 Forkhead box protein G1 Human genes 0.000 description 4
- 101710087964 Forkhead box protein G1 Proteins 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 206010052804 Drug tolerance Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000002123 RNA extraction Methods 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000026781 habituation Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 102100034746 Cyclin-dependent kinase-like 5 Human genes 0.000 description 2
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
- 101710107143 Dopamine receptor 1 Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 2
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 2
- 101000945692 Homo sapiens Cyclin-dependent kinase-like 5 Proteins 0.000 description 2
- 208000002740 Muscle Rigidity Diseases 0.000 description 2
- 208000008238 Muscle Spasticity Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 108091008611 Protein Kinase B Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 208000001970 congenital sucrase-isomaltase deficiency Diseases 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 238000010199 gene set enrichment analysis Methods 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000037023 motor activity Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 238000003068 pathway analysis Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 206010039722 scoliosis Diseases 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001457 vasomotor Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WBIZYAXYAGDQGK-ZZJOKYKRSA-N (2r)-2-amino-3-[[(2r)-2-amino-2-carboxyethyl]disulfanyl]butanoic acid Chemical compound OC(=O)[C@@H](N)C(C)SSC[C@H](N)C(O)=O WBIZYAXYAGDQGK-ZZJOKYKRSA-N 0.000 description 1
- HWPZZUQOWRWFDB-UHFFFAOYSA-N 1-methylcytosine Chemical compound CN1C=CC(N)=NC1=O HWPZZUQOWRWFDB-UHFFFAOYSA-N 0.000 description 1
- 102100022289 60S ribosomal protein L13a Human genes 0.000 description 1
- 102100022890 ATP synthase subunit beta, mitochondrial Human genes 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 208000024255 Audiogenic seizures Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102000008169 Co-Repressor Proteins Human genes 0.000 description 1
- 108010060434 Co-Repressor Proteins Proteins 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000681240 Homo sapiens 60S ribosomal protein L13a Proteins 0.000 description 1
- 101000903027 Homo sapiens ATP synthase subunit beta, mitochondrial Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 206010021588 Inappropriate affect Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 238000013381 RNA quantification Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 208000036353 Rett disease Diseases 0.000 description 1
- 206010039740 Screaming Diseases 0.000 description 1
- 102100028656 Sigma non-opioid intracellular receptor 1 Human genes 0.000 description 1
- 101710104750 Sigma non-opioid intracellular receptor 1 Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 101150109352 acr-16 gene Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000000729 hypotrophic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000010801 machine learning Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000012259 partial gene deletion Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 210000000513 rotator cuff Anatomy 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662395854P | 2016-09-16 | 2016-09-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2986807T3 true ES2986807T3 (es) | 2024-11-12 |
Family
ID=61619744
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17851614T Active ES2909557T3 (es) | 2016-09-16 | 2017-09-15 | Utilización de la pridopidina para el tratamiento del síndrome de Rett |
| ES22150695T Active ES2986807T3 (es) | 2016-09-16 | 2017-09-15 | Pridopidina para su uso en el tratamiento del síndrome de Rett |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17851614T Active ES2909557T3 (es) | 2016-09-16 | 2017-09-15 | Utilización de la pridopidina para el tratamiento del síndrome de Rett |
Country Status (13)
| Country | Link |
|---|---|
| EP (2) | EP3512506B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6977029B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN109982686A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2017326013B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR112019005040A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA3036984C (cg-RX-API-DMAC7.html) |
| DK (2) | DK4005570T3 (cg-RX-API-DMAC7.html) |
| ES (2) | ES2909557T3 (cg-RX-API-DMAC7.html) |
| HU (1) | HUE058314T2 (cg-RX-API-DMAC7.html) |
| IL (1) | IL265342B2 (cg-RX-API-DMAC7.html) |
| MX (1) | MX388845B (cg-RX-API-DMAC7.html) |
| PL (2) | PL3512506T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2018053280A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA122999C2 (uk) | 2013-06-21 | 2021-02-03 | Прайлінія Н'Юротерапьютікс Лтд. | Застосування придопідину для лікування хвороби гантінгтона |
| US11090297B2 (en) | 2013-06-21 | 2021-08-17 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating huntington's disease |
| EP3503890B1 (en) | 2016-08-24 | 2024-12-18 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine for treating dystonias |
| MX390627B (es) | 2016-08-24 | 2025-03-21 | Prilenia Neurotherapeutics Ltd | Uso de pridopidina para el tratamiento de la disminucion funcional. |
| US12102627B2 (en) | 2016-09-16 | 2024-10-01 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine for treating rett syndrome |
| CN109982686A (zh) | 2016-09-16 | 2019-07-05 | 普瑞尼亚医疗发展有限公司 | 普利多匹定用于治疗rett综合征的用途 |
| US12036213B2 (en) | 2017-09-08 | 2024-07-16 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| BR112021015346A2 (pt) | 2019-02-04 | 2021-10-05 | Prilenia Neurotherapeutics Ltd. | Uso de pridopidina de baixa dose para a doença de parkinson e outras doenças associadas ao parkinsonismo |
| CN116472043A (zh) * | 2020-10-20 | 2023-07-21 | 普瑞尼亚神经治疗有限公司 | 普利多匹定和类似物用于治疗焦虑和抑郁的用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
| CA2584831C (en) | 2004-10-13 | 2013-09-17 | Neurosearch Sweden Ab | Process for the synthesis of 4-(3-methanesulfonylphenyl)-1-n-propyl-piperidine |
| JP2013536825A (ja) | 2010-09-03 | 2013-09-26 | イバックス・インターナショナル・ゲーエムベーハー | ドパミン作動性安定化剤として有用なプリドピジンの重水素化類似体 |
| WO2013086425A1 (en) * | 2011-12-08 | 2013-06-13 | IVAX International GmbH | The hydrobromide salt of pridopidine |
| US20130267552A1 (en) | 2012-04-04 | 2013-10-10 | IVAX International GmbH | Pharmaceutical compositions for combination therapy |
| UA122999C2 (uk) | 2013-06-21 | 2021-02-03 | Прайлінія Н'Юротерапьютікс Лтд. | Застосування придопідину для лікування хвороби гантінгтона |
| JP6949487B2 (ja) * | 2014-01-22 | 2021-10-13 | プリレニア・ニューロセラピューティクス・エルティーディーＰｒｉｌｅｎｉａ Ｎｅｕｒｏｔｈｅｒａｐｅｕｔｉｃｓ Ｌｔｄ | プリドピジンの調節放出製剤 |
| EP4282479A3 (en) * | 2015-02-25 | 2024-02-21 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine to treat depression or anxiety |
| WO2016138135A1 (en) * | 2015-02-25 | 2016-09-01 | Teva Pharmaceuticals International Gmbh | Sigma-1 receptor modulators for treating huntington's disease |
| CN109982686A (zh) | 2016-09-16 | 2019-07-05 | 普瑞尼亚医疗发展有限公司 | 普利多匹定用于治疗rett综合征的用途 |
-
2017
- 2017-09-15 CN CN201780071045.XA patent/CN109982686A/zh active Pending
- 2017-09-15 DK DK22150695.9T patent/DK4005570T3/da active
- 2017-09-15 CA CA3036984A patent/CA3036984C/en active Active
- 2017-09-15 DK DK17851614.2T patent/DK3512506T3/da active
- 2017-09-15 AU AU2017326013A patent/AU2017326013B2/en active Active
- 2017-09-15 ES ES17851614T patent/ES2909557T3/es active Active
- 2017-09-15 JP JP2019514217A patent/JP6977029B2/ja active Active
- 2017-09-15 HU HUE17851614A patent/HUE058314T2/hu unknown
- 2017-09-15 EP EP17851614.2A patent/EP3512506B1/en active Active
- 2017-09-15 MX MX2019003069A patent/MX388845B/es unknown
- 2017-09-15 WO PCT/US2017/051803 patent/WO2018053280A1/en not_active Ceased
- 2017-09-15 BR BR112019005040A patent/BR112019005040A2/pt not_active Application Discontinuation
- 2017-09-15 PL PL17851614T patent/PL3512506T3/pl unknown
- 2017-09-15 PL PL22150695.9T patent/PL4005570T3/pl unknown
- 2017-09-15 ES ES22150695T patent/ES2986807T3/es active Active
- 2017-09-15 EP EP22150695.9A patent/EP4005570B1/en active Active
-
2019
- 2019-03-13 IL IL265342A patent/IL265342B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN109982686A (zh) | 2019-07-05 |
| JP2019532926A (ja) | 2019-11-14 |
| MX388845B (es) | 2025-03-20 |
| ES2909557T3 (es) | 2022-05-09 |
| PL4005570T3 (pl) | 2024-09-23 |
| IL265342A (en) | 2019-05-30 |
| AU2017326013B2 (en) | 2020-12-24 |
| DK3512506T3 (da) | 2022-04-19 |
| DK4005570T3 (da) | 2024-08-19 |
| AU2017326013A1 (en) | 2019-04-11 |
| EP3512506A1 (en) | 2019-07-24 |
| EP4005570A1 (en) | 2022-06-01 |
| MX2019003069A (es) | 2019-09-02 |
| CA3036984C (en) | 2023-07-18 |
| HUE058314T2 (hu) | 2022-07-28 |
| PL3512506T3 (pl) | 2022-05-30 |
| JP6977029B2 (ja) | 2021-12-08 |
| IL265342B2 (en) | 2023-06-01 |
| WO2018053280A1 (en) | 2018-03-22 |
| CA3036984A1 (en) | 2018-03-22 |
| EP3512506A4 (en) | 2020-05-27 |
| EP4005570B1 (en) | 2024-05-15 |
| EP3512506B1 (en) | 2022-01-26 |
| BR112019005040A2 (pt) | 2019-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2986807T3 (es) | Pridopidina para su uso en el tratamiento del síndrome de Rett | |
| ES2764480T3 (es) | Composiciones de combinación para tratar la enfermedad de Alzheimer y trastornos relacionados con zonisamida y acamprosato | |
| EA019571B1 (ru) | Применение сульфизоксазола для лечения болезни альцгеймера | |
| US20210401776A1 (en) | Method of treating refractory epilepsy syndromes using fenfluramine enantiomers | |
| JP2010504338A (ja) | 筋萎縮性側索硬化症（ＡＬＳ）の治療のための水素化ピリド［４，３−ｂ］インドール | |
| JP2010510314A (ja) | 精神遅滞、ダウン症候群、脆弱ｘ症候群および自閉症の治療方法 | |
| AU2018383098B2 (en) | Cyclobenzaprine treatment for agitation, psychosis and cognitive decline in dementia and neurodegenerative conditions | |
| JP2020535228A (ja) | 患者集団中のけいれん発作の数および頻度の低減におけるフェンフルラミン製剤の使用法 | |
| KR20160037169A (ko) | 레트 증후군 및 그를 위한 치료 | |
| CA3044355A1 (en) | Methods of enhancing immune response with everolimus, dactolisib or both | |
| US20240398778A1 (en) | Use of pridopidine for treating rett syndrome | |
| JP7744419B2 (ja) | レット症候群を治療するためのプリドピジンまたはその類似体の使用 | |
| CN108601772A (zh) | 用于治疗tdp-43蛋白质病的他克莫司 | |
| AU2021383325B2 (en) | Use of pridopidine and analogs for treating rett syndrome | |
| HK40009961B (en) | Use of pridopidine for treating rett syndrome | |
| RU2799049C2 (ru) | Способы лечения изменений поведения |