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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 description

DEENESFRITPL

Understanding the link between stroke and dementia

Cerebral small vessel disease (CSVD) is a common neurological condition that affects the small blood vessels in the brain responsible for supplying oxygen and nutrients. In CSVD, these vessels may become narrowed, blocked or weakened, leading to reduced blood flow and damage to the surrounding brain tissue, and resulting in various neurological symptoms and cognitive impairment. The key objective of the EU-funded SVDs-at-target project is to understand the role of blood pressure variability as a major risk factor in SVD and uncover the involvement of the blood-brain barrier and extracellular matrix. Insight into the molecular mechanisms of SVD will contribute to the design of effective interventions.

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.

Fields of science

Programme(s)

Topic(s)

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2015-two-stage

Funding Scheme

RIA - Research and Innovation action

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
Links
Total cost
€ 975 167,16

Participants (13)

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Last update: 22 January 2023

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

European Union, 2024