Myelin regeneration: from gene therapy to energy metabolism

Speaker: Dr. Vanja Tepavcevic
Institution: Departamento de Neurociencias, Facultad de Medicina y Enfermería, Universidad del País Vasco. Leioa, Spain
Place: CIPF conference room

Abstract: Multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS), is the leading cause of acquired neurological disability in young adults. Current treatments are immunomodulatory and provide temporary relief during relapses, but mostly lack an effect on disability progression, caused by axonal degeneration. Remyelination (myelin repair) of demyelinated axons reduces axonal degeneration in mice and patients, but this process eventually fails with disease progression. Thus, promoting remyelination in MS is a potential therapeutic strategy to prevent irreversible neurological deficits. So far, the search for pro-remyelinating agents has focused primarily on compounds that promote differentiation of oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the CNS, thus generation of new oligodendrocytes. Yet, clinical trials performed have shown modest functional benefits and scarce impact on the clinical outcome. In this talk, I will we argue that achieving clinical benefits in patients with MS will likely require complementary/alternative approaches to stimulate remyelination. I will present our recently published data on gene therapy as a therapeutically relevant strategy for stimulating OPC repopulation of demyelinating lesions that, as I will show, fails in the disease. Then, I will present our ongoing work based on the hypothesis that remyelination in MS fails due to metabolic deficit that prevents OPCs from synthesizing new myelin.