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WO2010010000A3 - Screening method, diagnostic method and small nucleic acid for the treatment of cns disorders - Google Patents

Screening method, diagnostic method and small nucleic acid for the treatment of cns disorders Download PDF

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Publication number
WO2010010000A3
WO2010010000A3 PCT/EP2009/058915 EP2009058915W WO2010010000A3 WO 2010010000 A3 WO2010010000 A3 WO 2010010000A3 EP 2009058915 W EP2009058915 W EP 2009058915W WO 2010010000 A3 WO2010010000 A3 WO 2010010000A3
Authority
WO
WIPO (PCT)
Prior art keywords
nucleic acid
treatment
cyp2c19
small nucleic
cell line
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
Application number
PCT/EP2009/058915
Other languages
French (fr)
Other versions
WO2010010000A2 (en
Inventor
Magnus Ingelman-Sundberg
Sarah Sim
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Karolinska Innovations AB
Original Assignee
Karolinska Innovations AB
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Karolinska Innovations AB filed Critical Karolinska Innovations AB
Publication of WO2010010000A2 publication Critical patent/WO2010010000A2/en
Publication of WO2010010000A3 publication Critical patent/WO2010010000A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/26Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/902Oxidoreductases (1.)
    • G01N2333/90245Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
    • G01N2333/90248Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14) with NADH or NADPH as one of the donors, and incorporation of one atom of oxygen 1.14.13
    • G01N2333/90251Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14) with NADH or NADPH as one of the donors, and incorporation of one atom of oxygen 1.14.13 with a definite EC number (1.14.13.-)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/04Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/10Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

A method of identifying a compound for use in the treatment of a mammal suffering from a CNS disorder, by determining the capacity of said compound of inhibiting the activity of CYP2C19 enzyme and/or of acting as a substrate for CYP2C19 enzyme. A cell derived from a neuronal stem cell line or embryonal cell line mimicking a neuronal stem cell line, which cell is overexpressing CYP2C19. A method of identifying a biological substance capable of being involved in the function of the CNS of a mammal by determining the capacity of said substance of interacting with CYP2C19 enzyme. A small nucleic acid molecule suitable for inhibiting the expression of a CYP2C19 gene for use as a medicament and a method of treatment of a CNS disorder by administering a therapeutically effective amount of the small nucleic acid molecule.
PCT/EP2009/058915 2008-07-21 2009-07-13 Screening method, diagnostic method and small nucleic acid for the treatment of cns disorders Ceased WO2010010000A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US8249208P 2008-07-21 2008-07-21
US61/082,492 2008-07-21

Publications (2)

Publication Number Publication Date
WO2010010000A2 WO2010010000A2 (en) 2010-01-28
WO2010010000A3 true WO2010010000A3 (en) 2010-05-06

Family

ID=41119952

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2009/058915 Ceased WO2010010000A2 (en) 2008-07-21 2009-07-13 Screening method, diagnostic method and small nucleic acid for the treatment of cns disorders

Country Status (1)

Country Link
WO (1) WO2010010000A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104928377A (en) * 2015-06-15 2015-09-23 广州金域医学检验中心有限公司 CYP2C19*3 gene polymorphism SNaPshot detection method and application
CN104946757A (en) * 2015-06-15 2015-09-30 广州金域医学检验中心有限公司 CYP2C19(*2,*3,*17) gene polymorphism SNaPshot detection method and application
CN104928380A (en) * 2015-06-15 2015-09-23 广州金域医学检验中心有限公司 CYP2C19*2 gene polymorphism SNaPshot detection method and application
CN104946759A (en) * 2015-06-15 2015-09-30 广州金域医学检验中心有限公司 CYP2C19*17 gene polymorphism SNaPshot detection method and application
CN104988221A (en) * 2015-06-30 2015-10-21 广州金域医学检验中心有限公司 Primer and method for detecting CYP2C9*3 gene polymorphism
CN104988222A (en) * 2015-06-30 2015-10-21 广州金域医学检验中心有限公司 Primer and method for simultaneously detecting polymorphism of CYP2C*2 and CYP2C*3 genes
CN108913766A (en) * 2018-07-17 2018-11-30 浙江大学 A kind of specific primer and probe and kit detecting depressed individuals chemical drug object therapeutic gene multisite mutation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087286A2 (en) * 2000-05-17 2001-11-22 Avi Biopharma, Inc. Antisense enzyme inhibitors for improving pharmacokinetics of a drug
WO2002012542A2 (en) * 2000-08-08 2002-02-14 Smithkline Beecham Plc Enzyme substrate
US20040229829A1 (en) * 1996-02-23 2004-11-18 The Board Of Regents Of The University Of Nebraska Enzyme inhibitors for metabolic redirection
WO2006105516A2 (en) * 2005-03-31 2006-10-05 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for diagnosing and treating neuropsychiatric disorders
US20080108076A1 (en) * 2006-11-07 2008-05-08 Stephanie Chissoe Genes associated with unipolar depression

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040229829A1 (en) * 1996-02-23 2004-11-18 The Board Of Regents Of The University Of Nebraska Enzyme inhibitors for metabolic redirection
WO2001087286A2 (en) * 2000-05-17 2001-11-22 Avi Biopharma, Inc. Antisense enzyme inhibitors for improving pharmacokinetics of a drug
WO2002012542A2 (en) * 2000-08-08 2002-02-14 Smithkline Beecham Plc Enzyme substrate
WO2006105516A2 (en) * 2005-03-31 2006-10-05 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for diagnosing and treating neuropsychiatric disorders
US20060257903A1 (en) * 2005-03-31 2006-11-16 Huda Akil Compositions and methods for diagnosing and treating neuropsychiatric disorders
US20080108076A1 (en) * 2006-11-07 2008-05-08 Stephanie Chissoe Genes associated with unipolar depression

Non-Patent Citations (16)

* Cited by examiner, † Cited by third party
Title
BONNET UDO: "Moclobemide: therapeutic use and clinical studies.", CNS DRUG REVIEWS SPRING 2003, vol. 9, no. 1, April 2003 (2003-04-01), pages 97 - 140, XP002549999, ISSN: 1080-563X *
CHO JOO-YOUN ET AL: "Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19", BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, vol. 53, no. 4, April 2002 (2002-04-01), pages 393 - 397, XP002569061, ISSN: 0306-5251 *
FLOCKHART D A: "Drug interactions and the cytochrome P450 system. The role of cytochrome P450 2C19.", CLINICAL PHARMACOKINETICS 1995, vol. 29 Suppl 1, 1995, pages 45 - 52, XP008118873, ISSN: 0312-5963 *
GRAM L F ET AL: "Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: A panel study", CLINICAL PHARMACOLOGY AND THERAPEUTICS, NATURE PUBLISHING GROUP, US, vol. 57, no. 6, 1 June 1995 (1995-06-01), pages 670 - 677, XP008113034, ISSN: 0009-9236 *
HÄRTTER SEBASTIAN ET AL: "The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19.", PHARMACEUTICAL RESEARCH JUL 2002, vol. 19, no. 7, July 2002 (2002-07-01), pages 1034 - 1037, XP002550002, ISSN: 0724-8741 *
INGELMAN-SUNDBERG MAGNUS ET AL: "Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy", PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON B BIOLOGICAL SCIENCES, vol. 360, no. 1460, August 2005 (2005-08-01), pages 1563 - 1570, XP002569058, ISSN: 0962-8436 *
LEE L S ET AL: "Evaluation of inhibitory drug interactions during drug development: Genetic polymorphisms must be considered", CLINICAL PHARMACOLOGY AND THERAPEUTICS, NATURE PUBLISHING GROUP, US, vol. 78, no. 1, 1 July 2005 (2005-07-01), pages 1 - 6, XP004969634, ISSN: 0009-9236 *
LEVIN T T ET AL: "Life-threatening serotonin toxicity due to a citalopram-fluconazole drug interaction: case reports and discussion", GENERAL HOSPITAL PSYCHIATRY, ELSEVIER SCIENCE PUBLISHING, NEW YORK, NY, US, vol. 30, no. 4, 1 July 2008 (2008-07-01), pages 372 - 377, XP022849616, ISSN: 0163-8343, [retrieved on 20080625] *
LIU Z Q ET AL: "Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes.", ACTA PHARMACOLOGICA SINICA JAN 2001, vol. 22, no. 1, January 2001 (2001-01-01), pages 85 - 90, XP002550001, ISSN: 1671-4083 *
MA XIAOCHAO ET AL: "Metabolism of melatonin by human cytochromes P450", DRUG METABOLISM AND DISPOSITION, vol. 33, no. 4, April 2005 (2005-04-01), pages 489 - 494, XP002569059, ISSN: 0090-9556 *
RUDBERG I ET AL: "Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients", CLINICAL PHARMACOLOGY AND THERAPEUTICS, NATURE PUBLISHING GROUP, US, vol. 83, no. 2, 1 February 2008 (2008-02-01), pages 322 - 327, XP008112958, ISSN: 0009-9236, [retrieved on 20070711] *
SALSALI MAHNAZ ET AL: "Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.", CELLULAR AND MOLECULAR NEUROBIOLOGY, vol. 24, no. 1, February 2004 (2004-02-01), pages 63 - 76, XP002550000, ISSN: 0272-4340 *
SHAW GERRY ET AL: "Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells", FASEB JOURNAL, vol. 16, no. 8, June 2002 (2002-06-01), pages 869 - 871, XP002569060, ISSN: 0892-6638 *
SIM ET AL: "A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants", CLINICAL PHARMACOLOGY AND THERAPEUTICS, NATURE PUBLISHING GROUP, US, vol. 79, no. 1, 1 January 2006 (2006-01-01), pages 103 - 113, XP005245006, ISSN: 0009-9236 *
STEIMER WERNER ET AL: "Amitriptyline or not, that is the question: Pharmacogenetic testing of CYP2D6 and CYP219 identifies patients with low or high risk for side effects in amitriptyline therapy", CLINICAL CHEMISTRY, vol. 51, no. 2, February 2005 (2005-02-01), pages 376 - 385, XP002569057, ISSN: 0009-9147 *
XU ZHEN-HUA ET AL: "Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes", BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, BLACKWELL SCIENTIFIC PUBL, GB, vol. 48, no. 3, 1 September 1999 (1999-09-01), pages 416 - 423, XP002500089, ISSN: 0306-5251 *

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