Project R-14697

Fatty acid elongation and desaturation in control of lesion progression and repair in multiple sclerosis. (Research)

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system (CNS) in which phagocytes such as microglia and macrophages play a crucial role. Severe, progressive types of MS are linked to chronic active lesions in the CNS, characterized by inflammatory demyelinating phagocytes that promote lesion development and prevent repair. There is a high need for novel, more effective therapies for these progressive forms of MS. Our recent data show that prolonged intracellular accumulation of myelin-derived lipids induces an inflammatory phenotype in phagocytes, and that enzymes of fatty acid synthesis drive the induction of this detrimental phenotype. We hypothesize that targeting these enzymes can skew phagocytes in MS towards a reparative phenotype that resolves inflammation and promotes remyelination. To prove this hypothesis, we define changes in fatty acid synthesis in phagocytes in MS lesions by combining innovative lipidomics and transcriptomics approaches. In addition, we elucidate if targeting fatty acid enzymes induces brain repair by making use of state-of-the-art cell- and, tissue culture, and animal models. Obtained results will lead to a better insight into lesion progression and repair in MS and the identification of new targets for the development of improved treatments for progressive MS.

01 January 2024 - 31 December 2027