EP2504024A2 - Méthode de thérapie et de diagnostic de morbus alzheimer - Google Patents

Méthode de thérapie et de diagnostic de morbus alzheimer

Info

Publication number
EP2504024A2
EP2504024A2 EP10757220A EP10757220A EP2504024A2 EP 2504024 A2 EP2504024 A2 EP 2504024A2 EP 10757220 A EP10757220 A EP 10757220A EP 10757220 A EP10757220 A EP 10757220A EP 2504024 A2 EP2504024 A2 EP 2504024A2
Authority
EP
European Patent Office
Prior art keywords
alzheimer
seq
disease
cytokine receptors
membrane
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.)
Withdrawn
Application number
EP10757220A
Other languages
German (de)
English (en)
Inventor
Helmut E. Meyer
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.)
Leibniz Institut fuer Analytische Wissenschaften ISAS eV
Original Assignee
Ruhr Universitaet Bochum
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 Ruhr Universitaet Bochum filed Critical Ruhr Universitaet Bochum
Priority to EP10757220A priority Critical patent/EP2504024A2/fr
Publication of EP2504024A2 publication Critical patent/EP2504024A2/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/45—Transferases (2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the tau protein As described above, the tau protein
  • a disadvantage of known diagnostic methods using the previously known diagnostics is that early and complete detection of high-risk patients fails and therefore a diagnosis or therapy is insufficient or even too late.
  • Tyrosine Receptor Kinases and SEQ ID No. 129 to SEQ ID No. 179 are to be assigned to the "membrane-bound cytokine receptors". Furthermore, the former are in the enzyme class EC 2.7.10.1
  • Receptor kinases or membranous cytokine receptors ". Also included are those analogous amino acid sequences that are due to the exchange of one or more multiple amino acid (s) in these sequences, yet have the desired function of a “tyrosine receptor kinases” or “membrane-bound cytokine receptors”.
  • Membrane-bound cytokine receptors are prepared synthetically, in particular in the form of a fusion peptide.
  • fusion peptides are known in the art, such as GST, cellulose-binding domain, green fluorescent protein, maltose
  • the invention relates to a target or its use for a medicament for the prophylaxis and treatment of Alzheimer's disease selected from tyrosine receptor kinases and / or membrane-bound cytokine receptors, in particular selected from the sequences SEQ ID No. 1 to SEQ ID No. 179.
  • a target binds with specific Alzheimer's disease
  • the invention also relates to an assay or
  • kinases or membrane-bound cytokine receptors are presented in vitro and tested with a sample or substances.
  • the invention relates to an assay system which
  • An assay or screening system may be, for example, the
  • Fusion peptides which are arbitrarily immobilized or fixed on a surface.
  • the surface is particularly suitable nitrocellulose or the like.
  • beads or spheres can be used and these are introduced, for example, in a preparative column.
  • the method according to the invention can be carried out using such an assay or corresponding device according to the invention.
  • the invention relates to:
  • tyrosine receptor kinases or membrane-bound cytokine receptors according to the invention in particular at least one of the sequences SEQ ID NO. 1 to SEQ ID No. 179 or parts or fragments thereof, represent such a diagnostic.
  • Alzheimer's disease-specific autoimmune antibodies can be detected, for example, by means of an assay or screening system according to the invention.
  • the invention relates to the apheresis of Alzheimer's disease specific
  • Autoimmune antibodies in the body fluids of a patient by means of the tyrosine receptor kinases or membrane-bound cytokine receptors according to the invention in particular at least one of the sequences SEQ ID NO. 1 to SEQ ID No. 179 or parts or fragments thereof, also in the form of a fusion peptide, for binding the specific Alzheimer's disease autoimmune antibodies.
  • the invention relates to an apheresis method for
  • Patients with tyrosine receptor kinases or membrane-bound cytokine receptors in particular at least one of the sequences SEQ ID NO. 1 to SEQ ID No. 179 or a fusion peptide thereof, or parts or fragments thereof, is brought outside the human body or animal into contact and the
  • Body fluid is returned to the human or animal. Furthermore, the invention relates to a medicament for the prophylaxis or treatment of Alzheimer's disease by means of
  • Cytokine receptors in particular at least one of the sequences SEQ ID NO. 1 to SEQ ID No. 179 - or in the form of a
  • Fusionspeptids, or parts and fragments thereof (collectively “active ingredients"), human or animal administered / administered
  • the active compounds according to the invention can be in the form of
  • the dosage units may contain, for example, 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose.
  • a single dose preferably contains the amount Active substance which is administered in one application and which usually corresponds to one, a half, a third or a quarter of a daily dose.
  • Carriers are solid, semi-solid or liquid
  • Preferred pharmaceutical formulations are tablets, dragees, capsules, pills, granules, suppositories, solutions, juice, suspensions and emulsions, pastes, ointments, gels,
  • Tablets, dragees, capsules, pills and granules may contain the active ingredient (s) in addition to the usual excipients, such as a) fillers and extenders, e.g. Starches, lactose, cane sugar, glucose, mannitol and silicic acid, b) binders, e.g.
  • Polyvinylpyrrolidone c) humectants, e.g. Glycerine, d) disintegrants, e.g. Agar-agar, calcium carbonate and
  • Sodium carbonate e) dissolution inhibitor, e.g. Paraffin and f) absorption enhancer, e.g. quaternary ammonium compounds, g) wetting agents, e.g. Cetyl alcohol, glycerol monostearate, h) adsorbents, e.g. Kaolin and bentonite and i)
  • dissolution inhibitor e.g. Paraffin
  • absorption enhancer e.g. quaternary ammonium compounds
  • wetting agents e.g. Cetyl alcohol, glycerol monostearate
  • adsorbents e.g. Kaolin and bentonite and i)
  • Lubricants for example talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under a) to i).
  • the tablets, dragees, capsules, pills and granules can be mixed with the usual, optionally opacifying
  • the active ingredient (s) may optionally also be incorporated with one or more of the excipients listed above
  • microencapsulated form is a microencapsulated form.
  • Morbus Alzheimer includes Alzheimer's disease or synonym dementia of the Alzheimer's type, namely a primary degenerative brain disease with progressive dementia usually beginning in the second half of life;
  • Acetylcholine synthesis detectable. Symptoms are initially memory disorders; in the further course there are restlessness,
  • the invention also relates to the identification of
  • the invention also relates to a method for
  • the patient to be examined tissue samples or
  • Body fluid blood, plasma taken, and the diagnosis is in vitro / ex vivo, ie outside the human or animal body.
  • Another task is to provide a
  • diagnostic device in particular an array or assay (e.g., immunoassay, ELISA, etc.), in particular a protein biochip (US6346413B1, US20050014292) in the broadest sense, an apparatus for performing the invention
  • the invention additionally relates to a kit for carrying out the methods according to the invention, in particular containing
  • Detecting reagents include e.g. Antibodies etc.
  • autoimmune antibodies can also be carried out with the aid of further protein diagnostic methods familiar to the person skilled in the art, in particular using radioactively or fluorescently labeled antibodies
  • bioanalytical methods such as immunohistochemistry, antibody arrays, Luminex, ELISA, immunofluorescence, Radioimmunoassays and other suitable bioanalytical methods, such as mass spectrometric methods, eg MRM (Multi Reaction Monitoring) or AQUA (absolute
  • the protein domains are produced as recombinant fusion proteins.
  • the fusion part includes one
  • Fusion protein e.g. in a Western blot
  • GST glutathione-S Transferase
  • RGSHis6 RGSHis6 tag
  • Protein domains can either be available from the market
  • the proteins expressed in in vitro or in cell culture are purified by affinity chromatography.
  • Concentration of the purified proteins is e.g. determined by amino acid analysis and adjusted to the desired value.
  • the proteins are applied by a spotting robot to a suitable support material, for example: nitrocellulose or PVDF membranes or glass or plastic substrates with a modified, protein-binding surface by means of contact or non-contact and immobilized.
  • the surface of the protein arrays is blocked immediately after production or before use (eg: with a Solution of milk powder or bovine serum albumin).
  • a defined volume of serum or plasma e.g., 10 or 100 pL
  • binding buffer in a defined ratio (e.g., 1: 100 or 1: 500) and a blocked protein array is hereby placed in a suitable container (e.g.
  • a labeled secondary antibody in a defined concentration (e.g., 100 pg / mL) and in a defined volume (e.g., 5 mL) over a defined concentration
  • the secondary antibody recognizes and binds human antibodies (e.g., IgG, IgM or IgG and IgM).
  • human antibodies e.g., IgG, IgM or IgG and IgM.
  • the label enables its detection, e.g.
  • detected secondary antibody e.g. with a
  • Fluorescence scanner This results in a quantitative or semiquantitative signal for each sample immobilized on the array (potential autoantigen and controls).
  • the experiment described is using blood samples Alzheimer's patient cohort (eg 100) as well as a comparable large selection of healthy and diseased controls
  • Classification method e.g. SVM, Support Vector Machine.
  • Alzheimer-specific diagnostic and / or pathologically relevant candidates are proteins whose signals are in the comparative study in the patients concerned
  • sequences of the invention SEQ ID No. 1-179 can be detected.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Neurology (AREA)
  • Hospice & Palliative Care (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne une méthode de thérapie et de diagnostic de Morbus Alzheimer ayant pour objet des récepteurs tyrosine-kinases et/ou des récepteurs membranaires à cytokines y compris des anticorps auto-immuns impliqués.
EP10757220A 2009-09-27 2010-09-27 Méthode de thérapie et de diagnostic de morbus alzheimer Withdrawn EP2504024A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10757220A EP2504024A2 (fr) 2009-09-27 2010-09-27 Méthode de thérapie et de diagnostic de morbus alzheimer

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP09171429 2009-09-27
PCT/EP2010/064289 WO2011036297A2 (fr) 2009-09-27 2010-09-27 Méthode de thérapie et de diagnostic de morbus alzheimer
EP10757220A EP2504024A2 (fr) 2009-09-27 2010-09-27 Méthode de thérapie et de diagnostic de morbus alzheimer

Publications (1)

Publication Number Publication Date
EP2504024A2 true EP2504024A2 (fr) 2012-10-03

Family

ID=43447835

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10757220A Withdrawn EP2504024A2 (fr) 2009-09-27 2010-09-27 Méthode de thérapie et de diagnostic de morbus alzheimer

Country Status (2)

Country Link
EP (1) EP2504024A2 (fr)
WO (1) WO2011036297A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2989158B1 (fr) 2012-04-04 2014-04-18 Commissariat Energie Atomique Procede de realisation d'un module d'echangeur de chaleur a au moins deux circuits de circulation de fluide.
US20170306400A1 (en) * 2014-04-03 2017-10-26 Tokyo Metropolitan Geriatric Hospital And Institute Of Gerontology Biomarker for diagnosis of aging or amyotrophia
WO2017050976A1 (fr) * 2015-09-23 2017-03-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Polypeptides ephb2 et leurs utilisations pour le diagnostic et le traitement du lupus
US11629340B2 (en) 2017-03-03 2023-04-18 Obsidian Therapeutics, Inc. DHFR tunable protein regulation
SG11202105476XA (en) * 2018-12-06 2021-06-29 Cytomx Therapeutics Inc Matrix metalloprotease-cleavable and serine or cysteine protease-cleavable substrates and methods of use thereof
CN116626294B (zh) * 2022-09-20 2024-07-09 菲创生物医学技术(广州)有限公司 盘状结构域受体2在诊断神经退行性疾病中的应用及相关的计算机可读介质

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US6346413B1 (en) 1989-06-07 2002-02-12 Affymetrix, Inc. Polymer arrays
ZA945372B (en) * 1993-07-21 1995-03-13 Regeneron Pharma Tyrosine kinase receptor
CA2122874A1 (fr) * 1994-04-29 1995-10-30 Anthony Pawson Tyrosine kinase de recepteur neural
US5814478A (en) * 1995-12-15 1998-09-29 Regeneron Pharmaceuticals, Inc. Tyrosine kinase receptors and ligands
WO1998045708A1 (fr) * 1997-04-08 1998-10-15 Sugen, Inc. Etude et traitement des maladies liees a des fonctions cellulaires specifiques de proteines tyrosines kinases receptrices
JP2002517241A (ja) * 1998-06-11 2002-06-18 アストラゼネカ アクチボラグ ヒト受容体チロシンキナーゼ
US6406921B1 (en) 1998-07-14 2002-06-18 Zyomyx, Incorporated Protein arrays for high-throughput screening
US20050227301A1 (en) * 2003-01-10 2005-10-13 Polgen Cell cycle progression proteins
US20060199226A1 (en) * 2005-03-02 2006-09-07 Schiffer Hans H Functional bioluminescence energy resonance transfer (BRET) assay to screen, identify and characterize receptor tyrosine kinase ligands
US20070128633A1 (en) * 2005-10-11 2007-06-07 Chembridge Research Laboratories, Inc. Cell-free protein expression systems and methods of use thereof
DE102006048201A1 (de) * 2006-10-11 2008-04-17 Ganymed Pharmaceuticals Ag Autoantigene zur verbesserten Diagnose, Prognose und Therapie von entzündlichen neurologischen Erkrankungen
CL2009000090A1 (es) * 2008-01-17 2009-07-24 Irm Llc Anticuerpo que se une al receptor de tirosina quinasa b (trkb); composicion que comprende el anticuerpo; metodo para reducir los niveles de glucosa en la sangre y/o el peso corporal en un individuo.
CA2714183A1 (fr) * 2008-02-14 2009-08-20 F. Hoffmann-La Roche Ag Prediction de toxicite de la moelle osseuse

Non-Patent Citations (2)

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Also Published As

Publication number Publication date
WO2011036297A2 (fr) 2011-03-31
WO2011036297A3 (fr) 2011-10-20

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