Characterizing Inflammatory and Neurodegenerative Pathways Driving Clinical Disease in Primary Progressive Multiple Sclerosis

Background: To develop more effective treatments for multiple sclerosis (MS), researchers require a better understanding of the biological processes that lead to susceptibility and progression, as well as animal models that emulate human disease. Unlike relapsing-remitting MS, progressive MS is not managed with current therapies, and the development of effective treatments is hindered due to the lack of animal models that resemble human disease.

Overview: To address this gap, this team of researchers developed the first mouse model of MS based on a human mutation (Nr1h3 gene) to understand the mechanisms involved in disease progression. The Nr1h3 gene mutation is known to cause severe and rapidly progressive MS in families. Preliminary analysis of this model has already revealed parallels with the human disease. Dr. Jacqueline Quandt and team will conduct a comprehensive characterization of this new animal model to identify the underlying biological pathways and mechanisms responsible for the onset of MS, thereby providing insight into the human disease. The researchers hypothesize that this study will reveal biological pathways not previously thought to be involved in progressive MS, which may point to new targets for therapy.

Impact: Development and understanding of a new animal model that better mimics human primary progressive MS will provide researchers with a needed tool to identify targets for therapy and evaluate novel therapeutics that better target progressive disease.

Project Status: In Progress