CHITOSANNEUROPROTECT

The iron burst inside the brain parenchyma induced by an acute ischemic stroke (AIS) or an intracerebral hemorrhage (ICH) is a major factor of secondary damage, notably by ferroptosis. Clinically approved iron chelates therapies did not show any positive effect on patient outcome, probably due to their insufficient chelating properties and cerebral bioavailability in case of a local iron burst. To overcome these limitations, an innovative iron chelator has been synthesized from a chitosan biopolymer and is currently under evaluation for a clinical application in dialysis. We obtained promising results in a pilot study, with an intracerebral administration in our AIS and ICH rat models. We propose 1/ to optimize the formulation to adapt its chelating capacity and bioavailability, 2/ to perform a multicentric preclinical trial in these two models to evaluate its effect by multimodal imaging using the innovative imaging biomarkers from our experimental platforms, 3/ to evaluate the feasibility of a minimally-invasive administration to prepare clinical translation. The project is coordinated by a vascular neurologist with his translational research team in multimodal imaging. The multidisciplinary consortium gathers a chemistry team, expert of nanocomposites and innovative bioactive devices, a translational research team, expert of AIS and ICH developing innovative inflammation imaging, a research team, expert of post AIS regenerative medicine and innovative imaging of cerebral metabolism and microcirculation, and the company who developed its first clinical application. Finally, the consortium will evaluate the potential for clinical transfer of the treatment, of the imaging biomarkers and of the administration route for a personalized patient care in stroke.