Exploring the Role of MITOchondrial ImmunoMETAbolism in Neuroinflammation: Mechanisms and New Targets for Progressive MS Treatment (MITO_META)

In multiple sclerosis (MS), the immune system attacks the central nervous system causing acute clinical symptoms, or relapses. Although there are therapies to stop relapses, most patients still develop a secondary progressive form of MS (P-MS) causing chronic disability, for which there is no cure. The damage in P-MS is caused by immune cells called mononuclear phagocytes (MPs). The aim of MITO_META is to reduce the harmful activation of MPs by targeting the way they produce energy (metabolism) in their powerhouse (mitochondria). I plan to use mouse models of MS (i) to abolish the harmful expression of a mitochondrial protein in MPs, and (ii) to investigate their changes in metabolism. I will then compare these findings to post-mortem data of people with progressive MS. This multi-step approach will lead to significant advances in our understanding of P-MS and allow us to develop new therapies to stop progression.