The goal of this project is to develop and characterize an innovative combined thrombolytic and anticoagulant approach for ischemic stroke. Ischemic stroke is a neurological deficit resulting from an insufficient blood supply to the brain due to the presence of a clot in a cerebral artery. In France, stroke is the 3rd leading cause of mortality (first in women) and the 1st cause of disability in adults, and it is estimated that there are 85,000 new cases of ischemic stroke per year, with a 20% increase in the upcoming years. The current standard of care of patients presenting an ischemic stroke is thrombectomy combined or not with thrombolysis. Thrombectomy is an endovascular procedure consisting in mechanically removing the clot with a stent retriever in a large occlusion of a cerebral artery. Thrombolysis, is the only pharmacological approach used in stroke patients to dissolve the clot. rtPA, which is the main clinically used pharmacological agent for thrombolysis, will activate plasminogen and convert it into plasmin that cleaves fibrin within the clot to destabilize it and restore the blood flow. Even though thrombolysis is the gold standard, it has many limitations. Therefore, there is an unmet medical need for more efficient therapeutic strategies to promote recanalization of cerebrovascular arteries with less harm to the patient. The main objective of this project is to develop and characterize new innovative thrombolytic strategies by specifically targeting an intravascular thrombus. The agents we developed will be characterized in in vitro and in vivo models of arterial thrombosis to evaluate their ability to bind a thrombus, to inhibit thrombin and to promote fibrin lysis. The thrombolytic potential will be then assessed in relevant mouse models of ischemic stroke and efficient doses will be determined. We will also determine whether these doses reduce the risk of bleeding as compared to currently used therapeutic agents in mouse models.
Madame Catherine Strassel (BIOLOGIE ET PHARMACOLOGIE DES PLAQUETTES SANGUINES : HÉMOSTASES, THROMBOSE, TRANSFUSION (U 1255))
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
PHIND Physiopathologie et imagerie des maladies neurologiques
BPPS BIOLOGIE ET PHARMACOLOGIE DES PLAQUETTES SANGUINES : HÉMOSTASES, THROMBOSE, TRANSFUSION (U 1255)
Help of the ANR 424,038 euros
Beginning and duration of the scientific project: March 2023 - 36 Months