2 000 000€ de la China Science Fund pour Erwan Bézard
Experts : Michele Morari – Ferrara; Antonio Pisani – Roma; Francesca Cicchetti – Québec, Anna Beyeler – Neurocentre Magendie qui viennent y superviser les manips. Sont concernés également de l’IMN : Benjamin Dehay, Pierre_Olivier Fernagut, Ludivine Breger, Gregory Porras, Sandra Dovero pour encadrer au plus près l’exécution des travaux. Une logistique importante pour un projet d’envergure.
The neurodegenerative diseases represent some of the greatest challenges for basic science and clinical medicine because of their prevalence, cost, complex biochemistry and pathology, and lack of mechanism-based treatments.
The PRIPRO project aim is to better understand the patho-physiological mechanisms related to specific protein aggregation and spreading that not only underlie its pathogenic role in several diseases but are also likely to bridge across these diseases. Here we propose working in parallel with α-synuclein (α-syn –Parkinson’s disease, Dementia with Lewy Body, Multiple System Atrophy, etc..), Abeta (Alzheimer’s disease, etc..), Tau (Alzheimer’s disease, Progressive Supranuclear Palsy, etc), TDP-43 (Amyotrophic lateral sclerosis, etc…), Huntingtin (Huntington’s disease, etc..). A likely mechanism linking these diseases relates to the prion-like properties of the aforementioned proteins. PRIPRO will assess them for the first time “face-to-face” in mice and non-human primates addressing fundamental questions remaining unsolved on the prion-like behaviour of these proteins (α-syn, Abeta, Tau, TDP-43, Huntingtin).
We hypothesize that a structure-function relationship for protein assemblies leads to their pathological accumulation and spreading depending on the different sites where proteins pathological forms are generated. Animals (mice and non-human primates) will be administered through different routes either protein strains isolated from the brain of patients developing different proteinopathies, or protein strains from recombinant proteins, or protein strains amplified by PMCA.
Effects of the various treatments will be compared at the behavioural, imaging, neurophysiological, pathological and biochemical levels.
A unique collection of brain, plasma and cerebrospinal fluid samples will be set up as a bio-bank to test disease biomarkers.
Such endeavour will finally constitute an in vivo screening tool for therapeutic identification and proof-of-concept in vivo studies will be conducted to achieve full translational demonstration in these ground-breaking models. PRIPRO frontier-breaking concepts, technologies and models bear the potential for fertilizing the entire field of Neuroscience as it unravels fundamental pathological mechanisms of neurodegenerative diseases and provides the roadmap tools for validating therapeutics aiming at interfering with their course.