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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

Descrizione del progetto

DEENESFRITPL

Comprendere il legame tra ictus e demenza

La cerebropatia microvascolare o malattia dei piccoli vasi (small vessel disease, SVD) è una condizione neurologica comune che colpisce i piccoli vasi sanguigni del cervello responsabili dell’apporto di ossigeno e nutrienti. Nella cerebropatia microvascolare, questi vasi possono restringersi, ostruirsi o indebolirsi, causando una riduzione del flusso sanguigno e danni al tessuto cerebrale circostante, con conseguenti vari sintomi neurologici e deficit cognitivi. L’obiettivo principale del progetto SVDs-at-target, finanziato dall’UE, è comprendere il ruolo della variabilità della pressione sanguigna come fattore di rischio principale nella cerebropatia microvascolare e scoprire il coinvolgimento della barriera emato-encefalica e della matrice extracellulare. La comprensione dei meccanismi molecolari della malattia dei piccoli vasi contribuirà alla progettazione di interventi efficaci.

Obiettivo

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.

Campo scientifico

Programma(i)

Argomento(i)

Invito a presentare proposte

H2020-PHC-2014-2015

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Bando secondario

H2020-PHC-2015-two-stage

Meccanismo di finanziamento

RIA - Research and Innovation action

Coordinatore

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

Mostra sulla mappa
Regione
Bayern Oberbayern München, Kreisfreie Stadt
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 975 167,16

Partecipanti (13)

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Ultimo aggiornamento: 22 Gennaio 2023

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

European Union, 2024