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Investigation of 960YT as a novel remyelination therapeutic for multiple sclerosis

Presenters Name: 
Megan Chappell
Co Presenters Name: 
Primary Research Mentor: 
Alban Gaultier
Secondary Research Mentor: 
Anthony Fernandez-Castaneda
2:00 - 3:15
Time of Presentation: 
2019 - 2:00pm to 3:15pm
Newcomb Hall Ballroom
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Double Hoo Research Grant

Multiple sclerosis, or MS, is an immune-mediated disease that causes the immune system to attack oligodendrocytes, which produce the myelin surrounding and protecting axons within the central nervous system (CNS). There is no cure for MS, and all current treatments are exclusively immunomodulatory and do not promote myelin repair, a process known as remyelination. Oligodendrocyte progenitor cells, or OPCs, are found throughout the CNS and can differentiate into myelinating oligodendrocytes, but fail to do so in MS lesions. Here we demonstrate that 960YT, a compound from an in silico bioactive compound screen, enhances remyelination in an in vitro culture system, as well as in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Treatment of 960YT increased expression of myelin markers MBP and CNP in OPCs cultured in both OPC differentiation conditions and proliferation conditions. In mice immunized with EAE, treatment of a low dose of 960YT did not have beneficial effects on disease severity. However, mice treated with a high dose of 960YT had lower clinical scores and incidence of disease than mice treated with vehicle, suggesting a high dose of 960YT may decrease EAE severity. Collectively, our findings demonstrate that 960YT may prove to be a viable remyelination therapeutic for demyelinating diseases such as multiple sclerosis, and may improve the quality of life for patients suffering from these diseases.