WO2008010225A3 - Enhancement of regulatory t cells' activity using statins - Google Patents

Enhancement of regulatory t cells' activity using statins Download PDF

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Publication number
WO2008010225A3
WO2008010225A3 PCT/IL2007/000906 IL2007000906W WO2008010225A3 WO 2008010225 A3 WO2008010225 A3 WO 2008010225A3 IL 2007000906 W IL2007000906 W IL 2007000906W WO 2008010225 A3 WO2008010225 A3 WO 2008010225A3
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WO
WIPO (PCT)
Prior art keywords
statins
regulatory
cells
activity
enhancement
Prior art date
Application number
PCT/IL2007/000906
Other languages
French (fr)
Other versions
WO2008010225A2 (en
Inventor
Gad Keren
Jacob George
Original Assignee
Medical Res Fund At The Tel Av
Gad Keren
Jacob George
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 Medical Res Fund At The Tel Av, Gad Keren, Jacob George filed Critical Medical Res Fund At The Tel Av
Publication of WO2008010225A2 publication Critical patent/WO2008010225A2/en
Publication of WO2008010225A3 publication Critical patent/WO2008010225A3/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
    • A61K31/21—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
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • 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
    • A61K31/435—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
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • Emergency Medicine (AREA)
  • Biophysics (AREA)

Abstract

The present invention concerns a method of enhancing the numbers and activity of naturally occurring CD4+CD25+ regulatory T cells using statins, e.g. atorvastatin. Treatment with statins increases the number of Tregs in vivo and in vitro with concomitant upregulation of their master transcriptional activator foxp3. The invention further concerns a method of treatment of diseases which are characterized by an impaired function of Tregs.
PCT/IL2007/000906 2006-07-18 2007-07-18 Enhancement of regulatory t cells' activity using statins WO2008010225A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US83144906P 2006-07-18 2006-07-18
US60/831,449 2006-07-18

Publications (2)

Publication Number Publication Date
WO2008010225A2 WO2008010225A2 (en) 2008-01-24
WO2008010225A3 true WO2008010225A3 (en) 2008-05-02

Family

ID=38814530

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2007/000906 WO2008010225A2 (en) 2006-07-18 2007-07-18 Enhancement of regulatory t cells' activity using statins

Country Status (1)

Country Link
WO (1) WO2008010225A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017044979A2 (en) * 2015-09-11 2017-03-16 Ventria Bioscience Inc. Lactoferrin compositions and methods for modulation of t cell subtypes and treatment of autoimmune diseases

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004003142A2 (en) * 2002-06-28 2004-01-08 Xcyte Therapies, Inc. Compositions and methods for restoring immune repertoire in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004003142A2 (en) * 2002-06-28 2004-01-08 Xcyte Therapies, Inc. Compositions and methods for restoring immune repertoire in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
CAVINATO REGIANE APARECIDA ET AL: "Pretransplant donor peripheral blood mononuclear cells infusion induces transplantation tolerance by generating regulatory T cells", TRANSPLANTATION (HAGERSTOWN), vol. 79, no. 9, May 2005 (2005-05-01), pages 1034 - 1039, XP002470524, ISSN: 0041-1337 *
CHENG ET AL: "Effects of Atorvastatin on Th polarization in patients with acute myocardial infarction", EUROPEAN JOURNAL OF HEART FAILURE, ELSEVIER, AMSTERDAM, NL, vol. 7, no. 7, December 2005 (2005-12-01), pages 1099 - 1104, XP005215517, ISSN: 1388-9842 *
HAKAMADA-TAGUCHI R ET AL: "Inhibition of Hydroxymethylglutaryl-Coenzyme A Reductase Reduces Th1 Development and Promotes Th2 Development", CIRCULATION RESEARCH 14 NOV 2003 UNITED STATES, vol. 93, no. 10, 14 November 2003 (2003-11-14), pages 948 - 956, XP002470525, ISSN: 0009-7330 *
LEUNG B P ET AL: "A novel anti-inflammatory role for simvastatin in inflammatory arthritis", JOURNAL OF IMMUNOLOGY 01 FEB 2003 UNITED STATES, vol. 170, no. 3, 1 February 2003 (2003-02-01), pages 1524 - 1530, XP002470526, ISSN: 0022-1767 *
SCHWARTZ ET AL: "The Case for Intensive Statin Therapy After Acute Coronary Syndromes", AMERICAN JOURNAL OF CARDIOLOGY, CAHNERS PUBLISHING CO., NEWTON, MA,, US, vol. 96, no. 5, 5 September 2005 (2005-09-05), pages 45 - 53, XP005045838, ISSN: 0002-9149 *
YOUSSEF S ET AL: "The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease", NATURE 07 NOV 2002 UNITED KINGDOM, vol. 420, no. 6911, 7 November 2002 (2002-11-07), pages 78 - 84, XP002470483, ISSN: 0028-0836 *

Also Published As

Publication number Publication date
WO2008010225A2 (en) 2008-01-24

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