Abstract Details

Title Finding New Targets for the Understanding and Treatment of Multiple Sclerosis: Modeling Multiple Sclerosis through Disease-Specific Neural Stem Cells

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-002

Objective We aim to demonstrate disease-specific variations in neuronal stem cell maturation in multiple sclerosis (MS) and identify opportunities for therapeutic intervention.

Background Investigation of the cellular and molecular mechanisms of neurodegenerative diseases is difficult due to the risk of obtaining central nervous system (CNS) tissue from patients. However, human induced pluripotent stem cells (iPSCs) can be derived from peripheral blood and differentiated into neuronal cells. This allows in vitro modeling of a disease of interest, via analysis of cells derived from patients with the disease compared to healthy controls. MS is the quintessential autoimmune demyelinating disorder of the CNS. However, a unifying understanding of the etiology of MS is lacking which may provide targets for regenerative cell-based therapies in MS.

Design/Methods Eight subjects with a confirmed diagnosis of MS were recruited from our neurology clinic along with age and gender matched controls. Consenting subjects underwent a peripheral blood draw and mononuclear cells were purified. Cells were reprogrammed via forced expression of a defined cocktail of genes promoting pluripotency (OCT4, SOX2, KLF4, MYC/NANOG, and LIN28). iPSCs were purified and differentiated into neural stem cells (NSCs) and then oligodendrocytes, astrocytes, and neurons which were confirmed via immunohistochemistry.

Results We have successfully generated iPSCs, NSCs, and all three mature neuronal lineages from both control and MS subjects. We are now comparing vulnerability, proliferation, and differentiation efficiency of the cells between the two study groups. Additionally, transcriptome analysis and genomic testing of each study group is currently underway to query candidate processes leading to such differences. We expect these results prior to the AAN Annual Meeting 2020.

Conclusions Our study is the first to our knowledge to explore intrinsic abnormalities in CNS cell populations derived from patients with MS, which may empower new therapies to repair demyelination and/or reestablish neurodegenerative losses.

Authors/Disclosures
Paul M. Elsbernd, MD (Brooke Army Medical Center) PRESENTER	Dr. Elsbernd has nothing to disclose.
Jon Williams, DO, PhD (Premier Physicians Network)	Dr. Williams has nothing to disclose.
Marcel Daadi, PhD (Texas Biomedical Research Institute)	The institution of Prof. Daadi has received research support from NIH. Prof. Daadi has received intellectual property interests from a discovery or technology relating to health care.

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