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WO2008148491A1 - Molécule 1 d'adhérence cellulaire neuronale en tant que biomarqueur de la maladie d'alzheimer - Google Patents

Molécule 1 d'adhérence cellulaire neuronale en tant que biomarqueur de la maladie d'alzheimer Download PDF

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Publication number
WO2008148491A1
WO2008148491A1 PCT/EP2008/004236 EP2008004236W WO2008148491A1 WO 2008148491 A1 WO2008148491 A1 WO 2008148491A1 EP 2008004236 W EP2008004236 W EP 2008004236W WO 2008148491 A1 WO2008148491 A1 WO 2008148491A1
Authority
WO
WIPO (PCT)
Prior art keywords
protein
disease
level
alzheimer
variant
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/EP2008/004236
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English (en)
Other versions
WO2008148491A8 (fr
Inventor
Peter Berndt
Bernd Bohrmann
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
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 F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of WO2008148491A1 publication Critical patent/WO2008148491A1/fr
Publication of WO2008148491A8 publication Critical patent/WO2008148491A8/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4709—Amyloid plaque core protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2814—Dementia; Cognitive disorders
    • G01N2800/2821—Alzheimer

Definitions

  • variant also relates to a post-translationally modified protein such as glycosylated protein.
  • a “variant” is also a peptide which has been modified after collection of the sample, for example by covalent or non-covalent attachment of a label, particularly a radioactive or fluorescent label, to the protein.
  • biomarker refers to molecules in an individual which are differentially present (i.e. present in increased or decreased levels) depending on presence or absence of a certain condition, disease, or complication.
  • biochemical markers are gene expression products which are differentially present (e.g., through increased or decreased level of expression or turnover) in presence or absence of a certain condition, disease, or complication.
  • a biomarker of the invention is a biochemical marker.
  • a biochemical marker is a protein, polypeptide or peptide.
  • the level of a suitable biomarker can indicate the presence or absence of a particular condition, disease, or risk, and thus allow diagnosis or determination of the condition, disease or risk.
  • the protein is comprised in a body fluid sample, and the amount of the protein in the body fluid sample is measured.
  • Binding of the ligand can be measured by any method known in the art.
  • the method is semi-quantitative or quantitative. Suitable methods are described in the following.
  • binding of a ligand may be measured directly, e.g., by NMR or surface plasmon resonance.
  • Labeling maybe done by direct or indirect methods.
  • Direct labeling involves coupling of the label directly (covalently or non-covalently) to the ligand.
  • Indirect labeling involves binding (covalently or non-covalently) of a secondary ligand to the first ligand.
  • the secondary ligand should specifically bind to the first ligand.
  • Said secondary ligand may be coupled with a suitable label and/or be the target (receptor) of tertiary ligand binding to the secondary ligand.
  • the use of secondary, tertiary or even higher order ligands is often used to increase the signal.
  • Suitable secondary and higher order ligands may include antibodies, secondary antibodies, and the well-known streptavidin- biotin system (Vector Laboratories, Inc.)
  • fluorescent labels include fluorescent proteins (such as GFP and its derivatives), Cy3, Cy5, Texas Red, Fluorescein, and the Alexa dyes (e.g., Alexa 568). Further fluorescent labels are available, e.g., from Molecular Probes (Oregon). Also the use of quantum dots as fluorescent labels is contemplated.
  • the present invention also relates to a kit comprising a means or an agent for measuring Neural cell adhesion protein 1 or a variant thereof.
  • the kit may additionally comprise a user's manual for interpreting the results of any measurement(s) with respect to determining whether an individual suffers from Alzheimer's Disease and/ or monitoring the progression of Alzheimer's Disease of an individual.
  • a user's manual for interpreting the results of any measurement(s) with respect to determining whether an individual suffers from Alzheimer's Disease and/ or monitoring the progression of Alzheimer's Disease of an individual.
  • such manual may include information about what measured level corresponds to a decreased level or increased level.
  • the proteins of interest may also be used as target. Therefore, the present invention provides a method of screening for a compound which interacts with Neural cell adhesion protein 1, or a variant thereof.
  • a suitable method is for example the method of screening for a compound which interacts with Neural cell adhesion protein 1, or a variant thereof, comprising a) contacting Neural cell adhesion protein 1, or a variant thereof with a compound or a plurality of compounds under conditions which allow interaction of said compound or a plurality of compounds with Neural cell adhesion protein 1, or a variant thereof; and b) detecting the interaction between said compound or plurality of compounds with Neural cell adhesion protein 1, or a variant thereof.
  • Grey matter tissue from frozen brain sections of the occipital association gyrus was mechanically dissected, and dried.
  • Each Protein lane was cut into 19 sections. Each section was digested using an established in-gel digest procedure by which tryptic digests of the proteins were obtained and dried in the lyophilisator.
  • the separated peptides were analyzed on the fly by a Thermo LTQ Iontrap. Each MS Scan was set to acquire a full mass spectrum between 400 and 1500 Da followed by seven MS/MS scans between 400 and 2000 Da of the top seven ions from the preceding MS scan. Relative collision energy for CID was set to 35%. Dynamic exclusion was enabled with a repeat count of 2, a repeat duration of 60 seconds, and an exclusion duration of 60 seconds. Altogether 38 LC-MS runs were performed for each Sample. Each run took 150 minutes. Data Evaluation

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Méthode d'évaluation de la maladie d'Alzheimer in vitro consistant à mesurer dans un échantillon (tel qu'un liquide organique) le niveau de la protéine 1 d'adhésion cellulaire neuronale ou d'une variante de cette protéine, un niveau modifié de cette protéine indiquant que l'individu souffre de la maladie d'Alzheimer. De plus, méthode de surveillance de la progression de la maladie d'Alzheimer in vitro, consistant à mesurer dans un échantillon (tel un liquide organique) le niveau de protéine 1 d'adhésion cellulaire neuronale ou d'une variante de cette dernière, une modification de niveau par rapport à un relevé antérieur des niveaux de ladite protéine ou d'une variante de celle-ci indiquant une progression de la maladie d'Alzheimer.
PCT/EP2008/004236 2007-06-04 2008-05-28 Molécule 1 d'adhérence cellulaire neuronale en tant que biomarqueur de la maladie d'alzheimer Ceased WO2008148491A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07109517 2007-06-04
EP07109517.8 2007-06-04

Publications (2)

Publication Number Publication Date
WO2008148491A1 true WO2008148491A1 (fr) 2008-12-11
WO2008148491A8 WO2008148491A8 (fr) 2009-11-05

Family

ID=39681004

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/004236 Ceased WO2008148491A1 (fr) 2007-06-04 2008-05-28 Molécule 1 d'adhérence cellulaire neuronale en tant que biomarqueur de la maladie d'alzheimer

Country Status (1)

Country Link
WO (1) WO2008148491A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004017816A2 (fr) * 2002-08-22 2004-03-04 Becton, Dickinson And Company Methodes de diagnostic de troubles neurologiques lies a la demence

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004017816A2 (fr) * 2002-08-22 2004-03-04 Becton, Dickinson And Company Methodes de diagnostic de troubles neurologiques lies a la demence

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MIRNICS ET AL: "P75 neurotrophin receptor regulates expression of neural cell adhesion molecule 1", NEUROBIOLOGY OF DISEASE, BLACKWELL SCIENTIFIC PUBLICATIONS, OXFORD, GB, vol. 20, no. 3, 1 December 2005 (2005-12-01), pages 969 - 985, XP005153884, ISSN: 0969-9961 *
TODARO LAURA ET AL: "Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type.", NEUROBIOLOGY OF DISEASE MAR 2004, vol. 15, no. 2, March 2004 (2004-03-01), pages 387 - 393, XP002492327, ISSN: 0969-9961 *

Also Published As

Publication number Publication date
WO2008148491A8 (fr) 2009-11-05

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