Methods of treatment and diagnostic of pathological conditions associated with intense stress

The present invention relates to a method for preventing or treating pathological conditions associated with intense stress such as Post-Traumatic Stress Disorder (PTSD) by targeting the endogenous PAI-1 (Type 1 Plasminogen Activator Inhibitor). In the present invention, inventors demonstrate that there is a shift in the balance between the expression of tPA and PAI-1 proteins in a hippocampal region of a preclinical model of Post-Traumatic Stress (PTSD), is responsible for the transition between moderate stress which increases memory and facilitates adaptation and intense stress intense stress which induce pathological memories. In conditions of moderate stress, glucocorticoid hormones (GC) increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK cascade strengthens memory. When stress is particularly intense, very high levels of GC then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. Accordingly, inhibition of PAI-1 activity represent a new therapeutic approach to this debilitating condition and PAI-1 body fluid level in patient after trauma could be a predictive biomarker of the subsequent appearance of PTSD.

Keywords: PTSD, Risk Prediction, Treatment Response, PAI-1
Patent Application number: EP20305702.1 on 25/06/2020
PCT/EP2021/067397 on 24/06/2021
Publications:
Mol Psychiatry 2021 Jan 28 Bouarab et al. PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory DOI: 10.1038/s41380-021-01024-1

Reference:

BIO19520-D1

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Pierre MAZOT
Pierre MAZOT
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Patent filling date: 2020-06-25

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