GESTE

Stroke is a neurological deficit which results from an interruption of cerebral blood flow, mainly due to the appearance of a clot that blocks a cerebral artery (ischemic stroke: 80% of cases). Such a clot has usually been formed in the upstream circulation, in the heart or in a ruptured atherosclerotic plaque in the carotid artery (40%). In the latter case, in addition to a mechanical and/or pharmacological removal of the intracerebral clot (thrombectomy and thrombolysis), carotid stenting is performed to prevent recurrence of stroke. The major complication of this procedure is carotid stent thrombosis (18% of cases), which results from the accumulation of platelets on the stent and represents an unsolved medical problem. The rate of mortality of patients presenting carotid stent thrombosis is very elevated reaching 50%. The main objective of the GESTE project is to evaluate the potential of glenzocimab, an agent which targets the GPVI of blood platelets, to efficiently prevent carotid stent thrombosis in new relevant innovative experimental models. The scientific and technical program relies on the development of novel innovative in vitro and in vivo models which requires in-depth collaboration between both partners to combine their expertise and knowledge on arterial thrombosis and drug development. We will use a macrofluidic model with the precise geometry of human carotid artery to allow implantation of clinically used stents in order to assess in vitro the importance of GPVI in stent thrombosis and to evaluate the effect of glenzocimab. In addition, the effect of glenzocimab will be evaluated in a new in vivo model of stent thrombosis in our humanized mouse for GPVI using intravital. Finally, a clinical study with a limited number of patients presenting stent thrombosis and in which the effect of glenzocimab will be studied will also be launched.