Differential expression of CNS-specific proteins in progressive EAE point to potential biomarkers for progressive MS

Abstract

Abstract The lack of reliable markers for assessing the progression of multiple sclerosis (MS) from the relapsing-remitting to the secondary progressive form hinders the ability for therapeutic intervention and results in continued physiological deterioration. To begin to address the urgent need for biomarkers of progressive MS we investigated proteome changes over the disease course of progressive experimental autoimmune encephalomyelitis (EAE) in NOD mice as a preclinical model of the disease using a high-throughput quantitative proteomic technique pioneered in our lab. In this study, we utilized this established proteomic technique as well as bioinformatics tools to prioritize key proteins whose expression level in the CNS correlated specifically with the progressive phase of disease in the NOD EAE model. Hierarchical clustering of timepoints indicate that samples cluster based on progression of disease. Specifically, late time points cluster separately from naïve and peak time points. Importantly, statistical testing identified proteins with differential expression in the CNS of mice across the time course of NOD EAE, several of which are CNS specific. We are seeking to detect corollary changes in these CNS-specific proteins in the serum, pointing to a minimally invasive means of monitoring disease progress and measuring drug efficacy. Our studies will provide proof-of-concept for identifying homologous human biomarkers to guide treatment in individual patients. Furthermore, our results may provide insights into mechanisms that contribute to disease pathology and offer additional therapeutic targets for slowing the progression of MS.