WO2010020822A1 - Thérapie d’hypertriglycéridémie induite par apolipoprotéine - Google Patents

Thérapie d’hypertriglycéridémie induite par apolipoprotéine Download PDF

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Publication number
WO2010020822A1
WO2010020822A1 PCT/GR2008/000055 GR2008000055W WO2010020822A1 WO 2010020822 A1 WO2010020822 A1 WO 2010020822A1 GR 2008000055 W GR2008000055 W GR 2008000055W WO 2010020822 A1 WO2010020822 A1 WO 2010020822A1
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WO
WIPO (PCT)
Prior art keywords
apociii
mice
abca1
vldl
triglyceride
Prior art date
Application number
PCT/GR2008/000055
Other languages
English (en)
Inventor
Kyriakos Kypreos E.
Original Assignee
University Of Patras
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 University Of Patras filed Critical University Of Patras
Priority to PCT/GR2008/000055 priority Critical patent/WO2010020822A1/fr
Publication of WO2010020822A1 publication Critical patent/WO2010020822A1/fr

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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
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/04—Uses of viruses as vector in vivo

Definitions

  • 'functional variant' extends to any variant of wild-type ABCA1 , which, like wild-type ABCA1 , will promote association of one or more apolipoproteins of concern, e.g apoCIII, with HDL.
  • apolipoproteins of concern e.g. apoCIII
  • the availability of human ABCA1 or any suitable natural or mutant version thereof may be increased in vivo such that association of one or more apolipoproteins of concern, e.g. apoCIII, or possibly additionally or alternatively, for example, any of apoE, apoA-l or apoA-ll, is favoured with HDL particles over VLDL particles.
  • treatment in accordance with the invention may also assist other aspects of metabolic syndrome such as insulin resistance, resulting in type Il diabetes, and coronary heart disease when linked with over-expression of one or more apolipoproteins leading to accumulation of triglyceride- rich VLDL with abnormal apolipoprotein composition, such as apoCIII- and triglyceride rich VLDL. Accumulation of such VLDL particles may arise through accumulation of excess plasma apoCIII whereby the normal route of biogenesis of apoCIII-containing HDL particles requiring functional ABCA1 is compromised.
  • an agent which provides ABCA1 can be expected to promote formation of apoCIII-rich HDL and thereby increase the ratio of apoCIII associated with HDL to apoCIII associated with VLDL towards the normal for non-disease controls.
  • VLDL of apoE "7' x apoA-l "7" mice infected with AdGFP-CIII g had a human apoCIII content of 3.32 ⁇ 0.37 mg/dl, while VLDL of ABCAT 7" mice infected with the same virus had a human apoCIII content of 11.78 ⁇ 0.23 mg/dl.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention porte sur une nouvelle approche thérapeutique du traitement d'une hypertriglycéridémie induite par apolipoprotéine CIII (apoCIII) liée à la surexpression d'apoCIII qui porte sur l'augmentation de la disponibilité du transporteur de lipide ABCA1 ou une variante fonctionnelle de celui-ci. La nouvelle approche thérapeutique favorise l'accumulation de apoCIII sur HDL (lipoprotéine haute densité), ce qui réduit l'accumulation de apoCIII sur VLDL (lipoprotéine de très faible densité) et l'inhibition ultérieure d'une lipase de lipoprotéine. Cette approche thérapeutique peut être étendue à une autre hypertriglycéridémie induite par apolipoprotéine ainsi qu'à d'autres aspects de la maladie du syndrome métabolique liés à l'accumulation de VLDL riche en triglycéride avec une composition d'apolipoprotéine anormale.
PCT/GR2008/000055 2008-08-19 2008-08-19 Thérapie d’hypertriglycéridémie induite par apolipoprotéine WO2010020822A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/GR2008/000055 WO2010020822A1 (fr) 2008-08-19 2008-08-19 Thérapie d’hypertriglycéridémie induite par apolipoprotéine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/GR2008/000055 WO2010020822A1 (fr) 2008-08-19 2008-08-19 Thérapie d’hypertriglycéridémie induite par apolipoprotéine

Publications (1)

Publication Number Publication Date
WO2010020822A1 true WO2010020822A1 (fr) 2010-02-25

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GR2008/000055 WO2010020822A1 (fr) 2008-08-19 2008-08-19 Thérapie d’hypertriglycéridémie induite par apolipoprotéine

Country Status (1)

Country Link
WO (1) WO2010020822A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016458A1 (fr) * 1995-11-01 1997-05-09 Kos Pharmaceuticals, Inc. Apolipoproteine e2 et traitement de la maladie d'alzheimer
US20030073614A1 (en) * 2001-10-17 2003-04-17 Schulman Ira G. Methods for affecting various diseases utilizing LXR compounds
WO2004085996A2 (fr) * 2003-03-20 2004-10-07 Albert Einstein College Of Medicine Of Yeshiva University Biomarqueurs permettant de determiner la longevite et la maladie et utilisations
WO2006044596A2 (fr) * 2004-10-15 2006-04-27 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Peptides helicoidaux amphipathiques a plusieurs domaines et leurs methodes d'utilisation
WO2006118805A2 (fr) * 2005-04-29 2006-11-09 The Regents Of The University Of California Peptides et mimetiques de peptides destines a traiter les pathologies caracterisees par une reaction inflammatoire

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016458A1 (fr) * 1995-11-01 1997-05-09 Kos Pharmaceuticals, Inc. Apolipoproteine e2 et traitement de la maladie d'alzheimer
US20030073614A1 (en) * 2001-10-17 2003-04-17 Schulman Ira G. Methods for affecting various diseases utilizing LXR compounds
WO2004085996A2 (fr) * 2003-03-20 2004-10-07 Albert Einstein College Of Medicine Of Yeshiva University Biomarqueurs permettant de determiner la longevite et la maladie et utilisations
WO2006044596A2 (fr) * 2004-10-15 2006-04-27 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Peptides helicoidaux amphipathiques a plusieurs domaines et leurs methodes d'utilisation
WO2006118805A2 (fr) * 2005-04-29 2006-11-09 The Regents Of The University Of California Peptides et mimetiques de peptides destines a traiter les pathologies caracterisees par une reaction inflammatoire

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BISOENDIAL RADJESH J ET AL: "Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein", CIRCULATION, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 107, no. 23, 17 June 2003 (2003-06-17), pages 2944 - 2948, XP009117169, ISSN: 0009-7322 *
KOLOVOU G D ET AL: "Tangier disease four decades of research: A reflection of the importance of HDL", CURRENT MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS BV, BE, vol. 13, no. 7, 1 January 2006 (2006-01-01), pages 771 - 782, XP009117171, ISSN: 0929-8673 *
SOUMIAN S ET AL: "ABCA1 and atherosclerosis", VASCULAR MEDICINE, ARNOLD, LONDON, GB, vol. 10, no. 2, 1 May 2005 (2005-05-01), pages 109 - 119, XP009117172, ISSN: 1358-863X *

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