Theragnostic targeting of extracellular matrix metalloproteinases and blood brain barrier disruption in subacute ischemic stroke
Abstract
Despite the remarkable progress in the care of acute stroke with thrombolysis and mechanical thrombectomy during last years, the clinical management of subacute ischemic stroke still remains limited due to the lack of effective treatments. Hence, establishing novel theragnostic 19F nanoprobes targeting the neurovascular unit can contribute to accelerate the approval of promising therapies for clinical subacute stroke. For this reason, the aim of IMatrix is to explore the diagnostic and therapeutic potential of targeting matrix metalloproteinases on Blood-Brain Barrier disruption (BBBd), vascular inflammation, leucocyte infiltration and haemorrhagic transformation during secondary ischemic damage using fundamental and clinical research approaches. Likewise, the evaluation of the dynamic of subacute ischemic stroke in humans is a necessary preliminary step for future clinical trials targeting these pathophysiological mechanisms. Together with the use of a large portfolio of specific imaging and contrast agents able to image BBBd and the use of human blood biomarkers will help us to gain new insights into the potential of targeting neurovascular unit as novel therapeutic approach for subacute ischemic stroke. Finally, the knowledge obtained in the framework of IMatrix has a strong translational potential that can easily be transferred to other neurological and neurodegenerative diseases with consequently benefits to patient quality of life and potential treatment cost savings.
Keywords
Imaging techniques
Patient cohorts
Animal studies
In vitro BBB models
Development of new tools and/or technologies
Call topic
Cerebrovascular
Proposed runtime
n/a - n/a
Project team
Abraham Martin (Coordinator)
Spain (AEI)
Monica Carril
Spain (AEI)
Philipp Boehm-Sturm
Germany (BMBF)
Maxime Gauberti
France (ANR)
Marie-Pierre Dehouck
France (ANR)
Domokos Mathe
Hungary (NKFIH)