CORDIS
EU research results

CORDIS

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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

Project information

Grant agreement ID: 666881

Status

Ongoing project

  • Start date

    1 January 2016

  • End date

    31 December 2021

Funded under:

H2020-EU.3.1.1.

  • Overall budget:

    € 5 998 300

  • EU contribution

    € 5 998 300

Coordinated by:

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

Germany

Objective

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.

Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

Address

Geschwister Scholl Platz 1
80539 Muenchen

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 975 167,15

Participants (12)

UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE

United States

EU Contribution

€ 580 375

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 450 000

KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 555 375

THE UNIVERSITY OF EDINBURGH

United Kingdom

EU Contribution

€ 576 031,25

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 555 375

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands

EU Contribution

€ 570 875

WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER

Germany

EU Contribution

€ 555 375

UNIVERSITEIT MAASTRICHT

Netherlands

EU Contribution

€ 512 369

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Germany

EU Contribution

€ 309 506

STROKE ALLIANCE FOR EUROPE

Belgium

EU Contribution

€ 45 025

GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Germany

EU Contribution

€ 22 826,60

ARTTIC

France

EU Contribution

€ 290 000

Project information

Grant agreement ID: 666881

Status

Ongoing project

  • Start date

    1 January 2016

  • End date

    31 December 2021

Funded under:

H2020-EU.3.1.1.

  • Overall budget:

    € 5 998 300

  • EU contribution

    € 5 998 300

Coordinated by:

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

Germany