WO2023174946A1 - Méthode précoce et non invasive d'évaluation du risque de maladie de parkinson chez un sujet - Google Patents

Méthode précoce et non invasive d'évaluation du risque de maladie de parkinson chez un sujet Download PDF

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Publication number
WO2023174946A1
WO2023174946A1 PCT/EP2023/056498 EP2023056498W WO2023174946A1 WO 2023174946 A1 WO2023174946 A1 WO 2023174946A1 EP 2023056498 W EP2023056498 W EP 2023056498W WO 2023174946 A1 WO2023174946 A1 WO 2023174946A1
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Prior art keywords
lrrk2
level
protein
disease
phosphorylated
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PCT/EP2023/056498
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English (en)
Inventor
Jean-Marc TAYMANS
Eugénie MUTEZ
Marie-Christine Chartier-Harlin
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INSERM (Institut National de la Santé et de la Recherche Médicale)
Université de Lille
Centre Hospitalier Universitaire De Lille
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Publication of WO2023174946A1 publication Critical patent/WO2023174946A1/fr

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    • 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
    • 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
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • 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
    • G01N33/6854—Immunoglobulins

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

Abstract

Dans le cadre de la présente invention, les inventeurs ont réalisé des études sur des vésicules extracellulaires isolées à partir d'échantillons d'urine afin d'évaluer le potentiel de biomarqueur des mesures de la voie LRRK2-Rab dans la maladie de Parkinson (MP) idiopathique et liée à LRRK2, ainsi que chez des rongeurs et des primates non humains ayant reçu des inhibiteurs. Leurs résultats montrent des modifications de la voie LRRK2-Rab dans les vésicules extracellulaires urinaires, à la fois dans la maladie et après un traitement par inhibiteur de la kinase LRRK2. Plus précisément, les inventeurs ont découvert dans une première cohorte que les taux de pS1292-LRRK2 étaient élevés chez les individus porteurs de la mutation LRRK2 G2019S, mais qu'ils ne différaient pas de manière notable entre les groupes en bonne santé et ceux atteints de la maladie de Parkinson, qu'ils soient ou non porteurs de la mutation LRRK2 G2019S. Dans une seconde cohorte, ils ont constaté que la MP était statistiquement associée à une augmentation des taux de Rab8 et à une diminution des taux de phosphorylation S910-LRRK2 et S935-LRRK2. Cette étude évalue les gènes LRRK2 et Rabs en tant que marqueurs pathologiques et pharmacodynamiques dans les échantillons d'urine humaine et cette analyse actuelle montre que les épitopes LRRK2 et Rabs sont modifiés dans les groupes de patients.
PCT/EP2023/056498 2022-03-15 2023-03-14 Méthode précoce et non invasive d'évaluation du risque de maladie de parkinson chez un sujet WO2023174946A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP22305293 2022-03-15
EP22305293.7 2022-03-15

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WO2023174946A1 true WO2023174946A1 (fr) 2023-09-21

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012062783A1 (fr) 2010-11-10 2012-05-18 F. Hoffmann-La Roche Ag Dérivés de pyrazole aminopyrimidine en tant que modulateurs du lrrk2
WO2012159079A1 (fr) * 2011-05-18 2012-11-22 The Parkinson's Institute Dosage de l'activité de lrrk2 dans la maladie de parkinson
WO2014059052A1 (fr) * 2012-10-09 2014-04-17 Uab Research Foundation Méthodes et compositions destinées au diagnostic et au traitement de la maladie de parkinson et au parkinsonisme
WO2019104086A1 (fr) 2017-11-21 2019-05-31 Denali Therapeutics Inc. Polymorphes et formes solides d'un composé de pyrimidinylamino-pyrazole, et procédés de production

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012062783A1 (fr) 2010-11-10 2012-05-18 F. Hoffmann-La Roche Ag Dérivés de pyrazole aminopyrimidine en tant que modulateurs du lrrk2
WO2012159079A1 (fr) * 2011-05-18 2012-11-22 The Parkinson's Institute Dosage de l'activité de lrrk2 dans la maladie de parkinson
WO2014059052A1 (fr) * 2012-10-09 2014-04-17 Uab Research Foundation Méthodes et compositions destinées au diagnostic et au traitement de la maladie de parkinson et au parkinsonisme
WO2019104086A1 (fr) 2017-11-21 2019-05-31 Denali Therapeutics Inc. Polymorphes et formes solides d'un composé de pyrimidinylamino-pyrazole, et procédés de production

Non-Patent Citations (47)

* Cited by examiner, † Cited by third party
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