Abstract

Development of a Novel Drug Discovery Platform for Progressive Multiple Sclerosis

Stephen Crocker, Associate Professor, Department of Neuroscience, University of Connecticut School of Medicine

Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) without any effective treatment. Patients with PPMS generally do not benefit from currently prescribed  immuno-modulatory therapies which can be effective among relapsing-remitting MS (RRMS) patients. Hence, promoting endogenous brain repair by promoting the differentiation of myelin-forming oligodendrocytes (OLs) is viewed as a potential strategy to halt and possibly restore neurologic function in patients with PPMS. This presentation will provide an update on our current approach to develop a novel drug screening assay that can be used to identify compounds with potential to promote brain regeneration in PPMS patients. The basis for this assay is our recently developed and characterized induced pluripotent stem (iPS) cell lines from PPMS patient samples which we have determined can be used to model the lesion environment of the PPMS brain. When compared against iPS cells from age-matched, non-diseased control cell lines we recently reported that the cells from all PPMS patients tested have an inherent defect in their ability to protect or promote myelin forming OLs. This work provides an innovative approach with personalized medicine potential because it models a crucial aspect of the disease microenvironment. Outcomes from this assay may have important implications for understanding re-myelination failure in PPMS that may have therapeutic potential to benefit other forms of MS.