This portfolio presents our multidisciplinary, transnosographic and translational strategy to treat neurovascular and neurodegenerative diseases.

 

Item 1 illustrates our translational research to explore pathophysiological mechanisms and pharmacological targets (Objective 1) in particular our experience with neurovascular coupling, i.e. the relationship between local neuronal activity and changes in blood flow cerebral.

This coupling has been studied at the cellular level by electrophysiology, at the organic level by vasomotor tests and in vivo by pharmacological approaches. It has made it possible to understand post-ischemic lesions and to explore neuroprotective strategies, for example in the field of intracerebral hemorrhages. Our team has thus mobilized its preclinical strengths to define or enrich the natural history of neurovascular and neurodegenerative diseases at all stages, in order to generate data that is more easily translatable into clinical practice and to initiate new clinical studies. We are also studying the consequences in terms of regulated cell death, notably ferroptosis, and pharmacological targets for example in PD.

A growing part of our research is the characterization of radiological, electrophysiological and biological biomarkers based on connected tools.

The aim (objective 2) is to develop translational and multimodal biomarkers of prognosis, endophenotypes and drug response, with biomarkers combined with more specific clinical assessment of several domains of motor skills, cognition and behavior. We rely in particular on our very large cohorts of patients, which we coordinate, and on our expertise in imaging, in particular on the dedicated 3T research MRI and very soon on the 7T MRI.

Item 2 illustrates this translational approach by developing the concept of “virtual biopsy” with anatomo-radiological analyzes using MRI in our vascular and degenerative animal models, which we then translate into our patient cohorts.

A very good illustration of this approach with item 3 is the prediction of long-term cognitive function after a minor stroke using functional connectivity. Another very relevant example is the development of biomarkers based on connected objects which make it possible to evaluate people in their natural environment.

Item 4 illustrates the immense interest in evaluating walking with connected insoles, walking being a crucial biomarker for health. Indeed, a reduction in walking speed is correlated with life expectancy. Biomarkers such as the 95th percentile of walking speed, validated by our team in collaboration with the start-up Feetme, will serve as a proxy in therapeutic trials.

 

This preclinical and translational research, supported by the development of original biomarkers, has fueled our therapeutic research (objective 3).

 

Item 5 illustrates that our better knowledge of the pathophysiology of cerebral hemorrhage has allowed us to develop an innovative triple therapeutic action, with RHU funding of 9 million euros.

Item 6 shows that we have demonstrated that ferroptosis is a prevalent form of cell death in PD models, enabling us to conduct major national and European multicenter therapeutic trials.

Item 7 also demonstrates our ability to generate new therapeutic concepts such as “brain infusion”, with a symptomatic approach using intracerebral dopamine in PD, and a neuroprotective approach based on the restorative power of blood platelets in ALS. (RHU).