Translational Neuropathology Unit
Multiple sclerosis (MS) is the most frequent chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) affecting people from young adulthood. While existing disease-modifying treatments effectively control peripheral immune responses and mitigate the relapse-associated inflammatory activity, they demonstrate limited efficacy in halting disease progression that occurs independently of relapses. Preventing or treating clinical progression is a major unmet need in MS. Growing evidence supports the role of compartmentalized inflammation within the leptomeninges and within the parenchyma, as occurring in chronic active lesions, in clinical progression.
- Decoding chronic inflammation in MS using advanced neuropathogical multi-omic techniques, combining single-cell transcriptomics, spatial transcriptomics, multiplex immunostaining and metabolomics of autopsy MS brain and spinal cord tissues classified according to different lesion pathological stages.
- Cellular modelling of chronic CNS inflammation using a human-IPSC glia-enriched 3D model to interrogate human neuronal-glia-microglia functional crosstalk and to identify and test relevant, druggable molecular mechanisms of chronic inflammation in MS.
- Set-up of a translation MRI platform that will allow testing the discovered key mechanisms of chronic inflammation using proof-of-concept MRI-based clinical trials.
Absinta M, Sati P, Reich DS. Advanced MRI and staging of multiple sclerosis lesions. Nat Rev Neurol. 2016; PMID: 27125632
Absinta M, Sati P, Schindler M, Leibovitch E, Ohayon J, Wu T, Meani A, Filippi M, Jacobson S, Cortese I, Reich DS. Poor outcome in MS lesions with persistent 7-tesla phase rim. J Clin Invest 2016; PMID: 27270171
Absinta M, Sati P, Masuzzo F, Nair G, Sethi V, Kolb H, Ohajon J, Wu T, Cortese I, Reich DS. Chronic active multiple sclerosis lesions are associated with disability in vivo. JAMA Neurol. 2019; PMID: 31403674
Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J, Fitzgerald KC, Song A, Liu P, Lin JP, Wu T, Johnson KR, McGavern DB, Schafer DP, Calabresi PA, Reich DS. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature 2021; PMID: 34497421
Maggi P, Bulcke CV, Pedrini E, Bugli C, Sellimi A, Wynen M, Stölting A, Mullins WA, Kalaitzidis G, Lolli V, Perrotta G, El Sankari S, Duprez T, Li X, Calabresi PA, van Pesch V, Reich DS, Absinta M. B cell depletion therapy does not resolve chronic active multiple sclerosis lesions. EBioMedicine. 2023; PMID: 37437310.