SVDs@Target is funded by the EU Horizon 2020 programme, with researchers in several European centres who are researching blood-brain barrier and vascular dysfunction in sporadic and genetic SVDs (INVESTIGATE@SVDs, ZOOM@SVDs) and treatments (TREAT@SVDs). Stroke and dementia are major health concerns in Europe, with cerebral small vessel disease serving as a critical link between them, accounting for over 30% of strokes and at least 40% of dementia cases. Despite the severe impact on health, effective treatments for SVDs are still lacking. The consortium “Small vessel diseases in a mechanistic perspective: Targets for Intervention in Stroke and Dementia (SVDs@target),” is funded by the European Union's Horizon 2020 program and includes leading scientists from institutions such as the University of Edinburgh, Ludwig-Maximilians-Universität Munich, and the University of Oxford. This network has made significant strides in understanding the mechanisms behind multiple SVDs. It combines the efforts of basic scientists and clinicians, utilising innovative animal models and well-characterised patient cohorts to uncover common mechanisms across different SVDs and understand their contribution to brain damage. SVDs@target aims to identify shared molecular, cellular, and physiological mechanisms that impair microvessel function in various SVDs. It explores how these defects lead to brain damage and investigate new therapeutic approaches using advanced technologies to develop treatments that could prevent strokes and dementia. Collaborating across multiple centres allows for a more diverse patient population, enhancing the generalisability and robustness of the findings. The SVDs@Target programme comprises three clinical studies investigating the blood-brain barrier and vascular dysfunction in sporadic and genetic SVDs (INVESTIGATE@SVDs, ZOOM@SVDs) and treatments (TREAT@SVDs). INVESTIGATE@SVDs: Imaging NeuroVascular, Endothelial and STructural Integrity in prepAration to TrEat Small Vessel Diseases INVESTIGATE-SVDs was an observational study conducted at three centres: Edinburgh, Maastricht, and Munich. It involved 45 patients with sporadic small vessel diseases (SVDs) and 30 patients with CADASIL. The primary aim was to enhance the understanding of SVD pathophysiology by examining the connections between blood-brain barrier integrity, cerebrovascular reactivity to CO2, intracranial vascular and CSF pulsatility, blood pressure and its variability, and the clinical and structural characteristics of SVD. “Investigate-SVDs recruits small vessel disease (SVD) patients to have advanced magnetic resonance imaging scans. SVD remains poorly understood, this study has great potential to further knowledge & ultimately improve outcomes for patients.” - Dr Michael Thrippleton, Research Fellow, HCPC-registered Clinical Scientist “Investigate@SVDs is the first time ever that patients with sporadic and genetic forms of SVD, that blood-brain barrier, cerebrovascular reactivity, vascular pulsatility and structural abnormalities, have been assessed in one study, and where the study took place not just at one but at three different sites. This represents a major step forward in understanding of SVDs and in enabling methodologies for future clinical trials of ways to prevent and treat SVDs.” - Professor Joanna Wardlaw, Chair of Applied Neuroimaging; Head of Neuroimaging Sciences and Edinburgh Imaging; Foundation Chair at the Dementia Research Institute; Row Fogo Centre Director PI: Professor Joanna Wardlaw, University of Edinburgh Edinburgh Imaging Collaborators: Dr Gordon Blair, Dr Fergus Doubal, Professor Ian Marshall, Dr Michael Thrippleton Image ZOOM@SVDs: Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI ZOOM@SVDs aimed to identify new markers of cerebral small vessel function in patients with both monogenic and sporadic small vessel diseases (SVDs). The project examined how these markers correlate with disease severity and progression. These indicators can aid in understanding the causes of SVDs and potentially serve as surrogate outcome measures in upcoming clinical trials, demonstrating the effectiveness of drugs targeting small vessel function. Image TREAT-SVDs (EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases) TREAT-SVDs was a randomised, open-label, crossover trial conducted across five centres: Edinburgh, Maastricht, Munich, Oxford, and Utrecht. The study included 75 patients with sporadic small vessel diseases (SVDs) and 30 patients with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). The primary goal was to evaluate whether the calcium channel blocker amlodipine improves small vessel function in patients with symptomatic SVDs, compared to the Angiotensin II type 1 receptor blocker losartan or the beta-blocker atenolol. The secondary goal was to determine if losartan has a more favourable effect on small vessel function than atenolol. “TREAT@SVD proves that imaging cerebrovascular reactivity is robust enough not only to be used in multicentre studies, but also that it is sensitive and reliable enough to use as an intermediary outcome in randomised clinical trials. It could be used for testing new drugs in the future.” Professor Joanna Wardlaw, Chair of Applied Neuroimaging; Head of Neuroimaging Sciences and Edinburgh Imaging; Foundation Chair at the Dementia Research Institute; Row Fogo Centre Director PI: Professor M Dichgans, Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität, Munich Image Collaborating Centres Centre for Clinical Brain Sciences, Edinburgh (UK) Ludwig-Maximilians-Universität Munich (Germany) Maastricht University Medical Centre (Netherlands) University of Oxford (UK) University of Copenhagen INSERM University of Utrecht University of Münster Technische Universität München University of Vermont GABO:mi Funders Stroke Association UK Key publications SVDs@target papers 30 Jun 21. Featured Paper. Imaging NeuroVascular, Endothelial & STructural Integrity in prepAration to TrEat Small Vessel Diseases. The INVESTIGATE-SVDs study Protocol. Part of the SVDs@Target Project. Blair, Gordon W et al. “Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project.” Cerebral circulation - cognition and behavior vol. 2 100020. 26 Jun. 2021, doi:10.1016/j.cccb.2021.100020 Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI: Rationale and design of the “ZOOM@SVDs” study Full record of research outputs SVDs-at-Target Edinburgh Research Explorer This article was published on 2024-08-27
