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Small vessel diseases in a mechanistic perspective: Targets for Intervention Affected pathways and mechanistic exploitation for prevention of stroke and dementia

Description du projet

DEENESFRITPL

Comprendre le lien entre l’accident vasculaire cérébral et la démence

La maladie des petits vaisseaux cérébraux (MPVC) est une affection neurologique courante qui touche les petits vaisseaux sanguins du cerveau responsables de l’apport d’oxygène et de nutriments. Dans le cas de la MPVC, ces vaisseaux peuvent se rétrécir, s’obstruer ou s’affaiblir, entraînant une réduction du flux sanguin et des lésions au tissu cérébral environnant, ce qui induit divers symptômes neurologiques et des déficiences cognitives. L’objectif principal du projet SVDs-at-target financé par l’UE est de comprendre le rôle de la variabilité de la pression artérielle en tant que facteur de risque majeur dans les maladies des petits vaisseaux et de révéler l’implication de la barrière hémato-encéphalique et de la matrice extracellulaire. La compréhension des mécanismes moléculaires de la maladie des petits vaisseaux contribuera à la conception d’interventions efficaces.

Objectif

Stroke and dementia rank among the most pressing health issues in Europe. Cerebral small vessel diseases (SVDs) have emerged as a central link between these two major co-morbidities. SVDs account for more than 30% of strokes and at least 40% of dementia cases. They encounter multiple distinct diseases that can be separated based on their underlying genetic defects, risk factors, and clinical presentations. Despite this profound impact on human health, there are no treatments with proven efficacy against SVDs. The applicants have made major progress in identifying key mechanisms involved in SVDs and their co-morbidities. We recently identified blood pressure variability as a major independent risk factor for multiple SVDs, stroke, and dementia and illuminated the roles of the blood brain barrier and the extracellular matrix in small vessel function. We further identified novel molecular pathways (TIMP3, LTBP1, TGFß) that are shared between different SVDs and thus point towards common mechanisms. This EU network, which brings together basic scientists and academic clinicians, will make use of novel animal models and expertly phenotyped patient cohorts to identify key mechanisms common to multiple SVDs and determine how these mechanisms contribute to individual SVDs. We will: i) identify common molecular, cellular, and physiological mechanisms that compromise the function of microvessels in different SVDs; ii) determine how these common mechanistic defects intersect to drive brain damage; and iii) validate the relevance of mechanisms through interventions in experimental systems (isolated microvessels and in vivo) and in patients (exploratory proof of concept trials). Our resources including novel animal models and state-of-the art technologies (e.g. proteomics & ultra-high field MRI) as well as expertise in clinical trials support the feasibility of the approach. In fact, studies by the applicants already revealed novel attractive targets for therapeutic intervention.

Champ scientifique

Programme(s)

Thème(s)

Appel à propositions

H2020-PHC-2014-2015

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Sous appel

H2020-PHC-2015-two-stage

Régime de financement

RIA - Research and Innovation action

Coordinateur

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Contribution nette de l'UE
€ 975 167,16
Adresse
GESCHWISTER SCHOLL PLATZ 1
80539 Muenchen
Allemagne

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Région
Bayern Oberbayern München, Kreisfreie Stadt
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 975 167,16

Participants (13)

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Dernière mise à jour: 22 Janvier 2023

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Permalink: https://cordis.europa.eu/project/id/666881/fr

European Union, 2024