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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.

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2015-two-stage

Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution
€ 975 167,16
Address
Geschwister Scholl Platz 1
80539 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (13)

UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE
United States
Net EU contribution
€ 580 375,00
Address
Waterman Building 340
05405 0160 Burlington

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Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Net EU contribution
€ 450 000,00
Address
Wellington Square University Offices
OX1 2JD Oxford

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KOBENHAVNS UNIVERSITET
Denmark
Net EU contribution
€ 555 375,00
Address
Norregade 10
1165 Kobenhavn

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
THE UNIVERSITY OF EDINBURGH
United Kingdom
Net EU contribution
€ 580 920,21
Address
Old College, South Bridge
EH8 9YL Edinburgh

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Region
Eastern Scotland Edinburgh
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Net EU contribution
€ 555 375,00
Address
Rue De Tolbiac 101
75654 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
Net EU contribution
€ 570 875,00
Address
Heidelberglaan 100
3584 CX Utrecht

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Region
West-Nederland Utrecht Utrecht
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Germany
Net EU contribution
€ 550 486,03
Address
Schlossplatz 2
48149 Muenster

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Region
Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITEIT MAASTRICHT
Netherlands
Net EU contribution
€ 512 369,00
Address
Minderbroedersberg 4
6200 MD Maastricht

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Region
Limburg (NL) Zuid-Limburg
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
Germany
Net EU contribution
€ 309 506,00
Address
Ismaninger Strasse 22
81675 Muenchen

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
STROKE ALLIANCE FOR EUROPE
Belgium
Net EU contribution
€ 45 025,00
Address
Rue Washington 40
1050 Brussels

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Other
Non-EU contribution
€ 0,00
GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Participation ended

Germany
Net EU contribution
€ 22 826,60
Address
Oskar Von Miller Ring 29
80333 Muenchen

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
ARTTIC

Participation ended

France
Net EU contribution
€ 219 391,25
Address
39 Rue Des Mathurins
75008 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
ARTTIC INNOVATION GMBH
Germany
Net EU contribution
€ 70 608,75
Address
Oskar-von-miller-ring 29
80333 Munchen

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00