WO2007061995A3 - Biomarkers for statin-induced myopathy or rhabdomyolysis - Google Patents

Biomarkers for statin-induced myopathy or rhabdomyolysis Download PDF

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Publication number
WO2007061995A3
WO2007061995A3 PCT/US2006/044987 US2006044987W WO2007061995A3 WO 2007061995 A3 WO2007061995 A3 WO 2007061995A3 US 2006044987 W US2006044987 W US 2006044987W WO 2007061995 A3 WO2007061995 A3 WO 2007061995A3
Authority
WO
WIPO (PCT)
Prior art keywords
statin
pdk4
twitching
glycolysis
fatty acid
Prior art date
Application number
PCT/US2006/044987
Other languages
French (fr)
Other versions
WO2007061995A2 (en
Inventor
Muhua Li
Original Assignee
Novartis Ag
Novartis Pharma Gmbh
Muhua Li
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 Novartis Ag, Novartis Pharma Gmbh, Muhua Li filed Critical Novartis Ag
Publication of WO2007061995A2 publication Critical patent/WO2007061995A2/en
Publication of WO2007061995A3 publication Critical patent/WO2007061995A3/en

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    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Abstract

The invention provides genes as predictive biomarkers of statin-induced muscle toxicity. Following statin administration, three types of skeletal muscle (soleus, gastrocnemius and extensor digitorum lateralis (EDL)), including fast-twitching and slow-twitching, were profiled and analyzed. Remarkably, for samples exhibiting myopathy, the three muscle types showed highly similar gene expression profiles. Genes involved in oxidation, apoptosis, and ubiquitin-dependent protein catabolism and proteolysis were significantly changed, suggesting extensive protein degradation. In addition, significant induction of genes involved in the regulation of glycolysis and fatty acid oxidation, such as PDK4, 6-phosphofructo-2-kinase, and acetyl-Coenzyme A carboxylase beta, were also observed. PDK4 phosphorylates and inactivates the pyruvate dehydrogenase complex, and is the key inducer of the metabolic switch from glycolysis to fatty acid oxidation.
PCT/US2006/044987 2005-11-21 2006-11-20 Biomarkers for statin-induced myopathy or rhabdomyolysis WO2007061995A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73863105P 2005-11-21 2005-11-21
US60/738,631 2005-11-21

Publications (2)

Publication Number Publication Date
WO2007061995A2 WO2007061995A2 (en) 2007-05-31
WO2007061995A3 true WO2007061995A3 (en) 2007-09-20

Family

ID=37898777

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/044987 WO2007061995A2 (en) 2005-11-21 2006-11-20 Biomarkers for statin-induced myopathy or rhabdomyolysis

Country Status (1)

Country Link
WO (1) WO2007061995A2 (en)

Families Citing this family (18)

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DE10203352A1 (en) 2002-01-29 2003-07-31 Basf Ag Process for the preparation of 7-dehydrocholesterol and / or its biosynthetic intermediate and / or secondary products in transgenic organisms
US7611902B2 (en) * 2006-06-12 2009-11-03 Zora Biosciences Oy Diagnostic method for myopathy
EP2257646A1 (en) 2008-02-29 2010-12-08 ISIS Innovation Limited Diagnostic methods
US9817001B2 (en) 2008-05-27 2017-11-14 Boston Heart Diagnostics Corporation Methods for determining LDL cholesterol treatment
US8470541B1 (en) 2008-09-27 2013-06-25 Boston Heart Diagnostics Corporation Methods for separation and immuno-detection of biomolecules, and apparatus related thereto
US8778618B2 (en) 2010-04-16 2014-07-15 The Johns Hopkins University Compositions and methods for characterizing a myopathy
US9541565B2 (en) 2011-04-08 2017-01-10 Zora Biosciences Oy Biomarkers for sensitive detection of statin-induced muscle toxicity
DK2508895T3 (en) * 2011-04-08 2015-10-19 Zora Biosciences Oy BIOMARKERS FOR SENSITIVE DETECTION OF STATIN-INDUCED MUSCLE TOXICITY
EP2694981A1 (en) * 2011-04-08 2014-02-12 Zora Biosciences OY Biomarkers for sensitive detection of statin-induced muscle toxicity
EP2766728B1 (en) 2011-10-13 2017-09-06 Boston Heart Diagnostics Compositions and methods for treating and preventing coronary heart disease
WO2014051510A1 (en) * 2012-09-28 2014-04-03 Marc Pilon Statin side effect assessment
US9828624B2 (en) 2013-07-24 2017-11-28 Boston Heart Diagnostics Corporation Driving patient compliance with therapy
CA3005158A1 (en) 2014-11-06 2016-05-12 Scholar Rock, Inc. Anti-pro/latent-myostatin antibodies and uses thereof
WO2016081471A1 (en) 2014-11-17 2016-05-26 Boston Heart Diagnostic Corporation Cardiovascular disease risk assessment
LT3350220T (en) 2015-09-15 2021-09-27 Scholar Rock, Inc. Anti-pro/latent-myostatin antibodies and uses thereof
CN109071645A (en) 2016-01-08 2018-12-21 供石公司 Anti- Promyostatin/latent flesh amicine antibody and its application method
KR102271635B1 (en) 2016-06-13 2021-07-06 스칼러 락, 인크. Uses and Combination Therapies of Myostatin Inhibitors
FI3565592T3 (en) 2017-01-06 2023-05-10 Scholar Rock Inc Treating metabolic diseases by inhibiting myostatin activation

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
KAMEYAMA YOSHIO ET AL: "FUNCTIONAL CHARACTERIZATION OF SLCO1B1 (OATP-C) VARIANTS, SLCO1B1*5, SLCO1B1*15 AND SLCO1B1*15+C1007G, BY USING TRANSIENT EXPRESSION SYSTEMS OF HELA AND HEK293 CELLS", PHARMACOGENETICS AND GENOMICS, LIPPINCOTT WILLIAMS & WILKINS, PHILADELPHIA, PA, US, vol. 15, no. 7, July 2005 (2005-07-01), pages 513 - 522, XP008076207, ISSN: 1744-6872 *
MORIMOTO KAORI ET AL: "A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy.", DRUG METABOLISM AND PHARMACOKINETICS DEC 2004, vol. 19, no. 6, December 2004 (2004-12-01), pages 453 - 455, XP008077728, ISSN: 1347-4367 *
MOTOJIMA K ET AL: "Fibrates and statins rapidly and synergistically induce pyruvate dehydrogenase kinase 4 mRNA in the liver and muscles of mice", BIOLOGICAL AND PHARMACEUTICAL BULLETIN 2003 JAPAN, vol. 26, no. 7, 2003, pages 954 - 958, XP008077725, ISSN: 0918-6158 1347-5215 *
SCHACHTER MICHAEL: "Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.", FUNDAMENTAL & CLINICAL PHARMACOLOGY FEB 2005, vol. 19, no. 1, February 2005 (2005-02-01), pages 117 - 125, XP002429327, ISSN: 0767-3981 *
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VERMES ANDRAS ET AL: "Genetic polymorphisms in cytochrome P450 enzymes: effect on efficacy and tolerability of HMG-CoA reductase inhibitors.", AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS : DRUGS, DEVICES, AND OTHER INTERVENTIONS 2004, vol. 4, no. 4, 2004, pages 247 - 255, XP008077719, ISSN: 1175-3277 *
WILKE RUSSELL A ET AL: "Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage.", PHARMACOGENETICS AND GENOMICS JUN 2005, vol. 15, no. 6, June 2005 (2005-06-01), pages 415 - 421, XP008077717, ISSN: 1744-6872 *

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