Neurobiology of multiple sclerosis: from basic science to clinical translation
ECTRIMS Online Library. Lubetzki C. Oct 12, 2018; 232078; 326
Catherine Lubetzki
Catherine Lubetzki

Abstract: 326

Type: Plenary Session

Abstract Category: N/A

Clinical disability in multiple sclerosis mostly relates to irreversible neuronal/axonal damage and loss. Such axonal pathology is likely to take place early in disease evolution, before becoming clinically eloquent years later, after reaching clinical threshold. Preventing neurodegeneration therefore represents a major challenge and unmet need in multiple sclerosis.
Recently the many and not exclusive causes of neuronal damage in multiple sclerosis have been deciphered. Neuronal alterations can be driven by the direct impact of the inflammatory cascade, and such changes can occur independently of demyelination. In contrast, other neuronal/axonal changes are the direct consequence of myelin disruption. Redistribution of voltage dependent sodium channels along the naked axons or axonal metabolic dysfunction due to disruption of oligodendrocyte coupling are examples of such “demyelination-dependent” axonal changes observed in a non inflammatory environment.
Prevention of neurodegeneration can be achieved through the development of neuroprotective drugs. Promoting remyelination is an alternative strategy for neuronal protection, as evidenced by both experimental studies and neuropathological analysis of multiple sclerosis demyelinated and remyelinated lesions on the one hand, by imaging methods in multiple sclerosis patients on the other hand.
I will review some recent studies generated using different and complementary experimental models, which have clarified the different cellular and molecular steps involved in the process of endogenous myelin repair. These results have paved the way for the identification of therapeutic targets, and to the development of screening tools to identify novel therapeutic candidates for myelin repair. After many years of experimental studies, clinical translation is ongoing in patients with multiple sclerosis. I will present and discuss the results of the few completed early phase clinical trials focusing on strategies aimed at promoting endogenous myelin repair and neuroprotection, as well as the rationale of studies that should take place in the near future.
Disclosure: CL participated to advisory boards for Roche, Biogen, Merck-Serono, Genzyme, Vertex. CL had a scientific collaboration with Vertex pharmaceutical company and has an ongoing scientific collaboration with Merck Serono

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