Maxime Donadieu
Maxime Donadieu is a French visiting post-doctoral fellow. After a Bachelor in Biology with a major in Computational Neurosciences (2009-2012, Aix Marseille University), he decided to continue with a Master in Cellular Neurosciences (2013-2015, Aix Marseille University). He was recruited by Siemens S.A.S in 2015, in collaboration with the CRMBM lab (UMR 7339, Aix Marseille University), as an Engineer and also a PhD student. His PhD was focused on the development and the application of MR spectroscopy sequences on healthy subject and MS patients at high (3T) and ultra-high (7T) fields. He defended his PhD in December 2017 and moved in TNS lab in April 2018. The core of his project in TNS is to develop and use translational imaging (conventional, non-conventional MRI and PET scan) but also histology and immunochemistry on EAE marmoset model to understand and quantify the de/remyelination and neurodegenerative processes. The main objective of this project is to develop a remyelinating therapy relevant for MS patient.
Marmoset EAE as a faithful model to study multiple sclerosis
Experimental autoimmune encephalomyelitis (EAE) is a widely used preclinical model to study pathophysiology of multiple sclerosis (MS), develop and optimize imaging techniques and test potential new therapeutics. Rodent EAE is the most common animal model in the MS field. However, despite its high level of pathological complexity compared to other models, it rarely develops lesions in the brain and hardly replicates key aspects of the disease.
Marmoset EAE has shown remarkable similarities with MS from both imaging, histological and molecular points of view. EAE WM lesions generally develop in the brain around a central vein and slowly expand over time. During the acute inflammatory phase, WM lesions present T and B lymphocyte infiltration and activated macrophages/microglia alongside myelin loss and neuronal damage.
Cortical pathology has taken a major role in disease progression. However, detecting cortical lesion in vivo using clinical MRI is challenging. Moreover, little is known about cortical lesion formation and development. Cortical pathology also occurs in marmoset EAE and is now actively being investigated in vivo using MRI sequences. Mimicking human MS, marmoset EAE presents subtype of cortical lesions disseminated in time and space over the EAE disease course. Those lesions feature demyelination with relative sparing of neuronal somata; activated macrophages/microglia as well as T and B cell infiltrates and in nearby meninges without any follicular organization.
Remyelination is a crucial aspect of tissue repair and became an important therapeutic target in the MS field. Marmoset EAE presents spontaneous remyelination in nearly half of WM lesions detected both by conventional MRI and histology. Relative to histology, MRI can predict myelination status with high sensitivity and specificity; opening a path to study in vivo putative remyelinating therapies in marmoset.
In summary, marmoset EAE shows remarkable similarities with human MS with respect to WM, gray matter, and SC pathologies, and thus places itself as a promising model to study the overall mechanisms and dynamics of MS.
