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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

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.

Field of science

  • /medical and health sciences/basic medicine/neurology/stroke

Call for proposal

H2020-PHC-2015-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

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
Address
Waterman Building 340
05405 0160 Burlington
Activity type
Higher or Secondary Education Establishments
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 450 000
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 555 375
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 576 031,25
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 555 375
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
EU contribution
€ 570 875
Address
Heidelberglaan 100
3584 CX Utrecht
Activity type
Higher or Secondary Education Establishments
WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Germany
EU contribution
€ 555 375
Address
Schlossplatz 2
48149 Muenster
Activity type
Higher or Secondary Education Establishments
UNIVERSITEIT MAASTRICHT
Netherlands
EU contribution
€ 512 369
Address
Minderbroedersberg 4-6
6200 MD Maastricht
Activity type
Higher or Secondary Education Establishments
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
Germany
EU contribution
€ 309 506
Address
Ismaninger Strasse 22
81675 Muenchen
Activity type
Higher or Secondary Education Establishments
STROKE ALLIANCE FOR EUROPE
Belgium
EU contribution
€ 45 025
Address
Rue Washington 40
1050 Brussels
Activity type
Other
GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Participation ended

Germany
EU contribution
€ 22 826,60
Address
Oskar Von Miller Ring 29
80333 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ARTTIC
France
EU contribution
€ 290 000
Address
Rue Du Dessous Des Berges 58A
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)