Circulating CNS Cell-Derived Extracellular Vesicle Based Biomarkers to Identify Neurodegeneration and Glial Activation in Multiple Sclerosis
Abstract
Extensive synaptic loss is noted in MS brain and spinal cord samples and may independently drive disability progression. The mechanism of synaptic loss may be related to complement deposition and subsequent synaptic engulfment by phagocytic cells. Extracellular vesicles (EVs)are produced by all cells in the body and have both physiological and pathological roles. Neuronally-enriched (NEVs) and astrocyte-enriched (AEVs) EVs can be isolated from peripheral blood using immunoprecipitation for cell-specific markers. SPRINT-MS was a phase 2, randomized, placebo-controlled trial assessing the effect of ibudilast on several measures of tissue destruction in 255 participants with progressive MS. This trial included deep clinical and imaging phenotyping in addition to collection of biospecimens, making it an ideal cohort to evaluate the utility of these biomarkers. We will utilize plasma from the SPRINT-MS cohort to isolate NEVs and AEVs using an extensively validated method. We will then measure synaptic protein levels (synaptophysin and synaptopodin) in NEVs and complement component levels in AEVs. We will utilize mixed-effects models to examine both cross-sectional and longitudinal relationships between EV-based measures and clinical (EDSS, MSFC) and imaging (MRI and OCT) based measures and examine trajectories in the two treatment groups to determine whether these novel measures are good correlates for disease progression and monitoring of the effects of putative neuroprotective agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2023
- Accession Number
- AD1216086
Entities
People
- Pavan Bhargava
Organizations
- Johns Hopkins University