Recently, we used a MS animal model to perform high-throughput sequencing of astrocytes’ transcriptome during disease progression. Our data shows a surprising up-regulation of glycolytic and tricarboxylic acid (TCA) cycle regulatory genes. These results are in line with data from other fields, showing that a TCA cycle increase in monocytes is associated with a stronger immune response. Hence, we hypothesize that TCA cycle upregulation in MS astrocytes, is contributing to exacerbate brain inflammation leading to myelin damage. For that reason, we propose metabolic reprogramming as a novel therapeutic approach in MS. Our aim is testing itaconate treatment in MS animal models and evaluate metabolic reprogramming efficiency and treatment efficacy by using state-of-the-art metabolomic approaches, in vivo magnetic resonance spectroscopy (MRS), and functional electrophysiological evaluations of nerve conduction