Research Assistant II
Toby B. Lanser, Patrick Da Silva, Christian Barro, Mahsa Khayat-Khoei, Howard L. Weiner
Howard L Weiner
Multiple Sclerosis (MS) is a debilitating autoimmune disease of the central nervous system (CNS), characterized by demyelination of the brain and spinal cord. Driven by chronic inflammation and immune self-stimulation, this demyelination leads to, if untreated, irreversible clinical and cognitive decline. MS is split into two main categories: progressive and relapsing-remitting. In patients the former relates to worsening neurologic function and cognitive decline, while the latter relates to worsening symptoms followed be a period of remission. By leveraging single-cell RNA sequencing (scRNA-seq) of 6 healthy controls, 6 relapsing remitting MS (RRMS), 9 progressors, and 4 secondary progressive MS (SPMS) non-progressors, we present the first roadmap of the transcriptional dynamics underpinning the differences in RRMS and varying types of progressive MS. Additionally, for the first time, we show how, transcriptionally, blood monocytes differ from secondary progressive non-progressive from SPMS, enabling the modeling of the bifurcation of progression and non-progression after a relapsing-remitting phase. This work lays the foundation for the description, prediction, and modeling of progressive MS disease states, enabling future work to identify pathological processes that contribute to MS progression and new targets for therapeutic intervention.
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the immune system attacking and degrading the brain and spinal cord. As an autoimmune disorder, the root cause of MS is engrained in an over-reactive immune whose warped goal is to attack one’s own body. MS is split into two main categories: progressive and relapsing-remitting. In patients the former relates to worsening neurologic function and cognitive decline, while the latter relates to worsening symptoms followed be a period of remission. Progressive disease is currently untreatable, and patients progress in their clinical symptoms without entering a remitting state. Recent studies suggest that inflammation in the CNS could be driven by a group of cells from the blood who infiltrate the brain. Here, we survey these cells from progressive, non-progressive, and relapsing MS patients, with the goal of, for the first time, describing how these cells act between progressive and non-progressive states. Our findings aid future work focusing on potential biomarkers of progression, therapeutic targets, modeling the disease to predict progression.