Project R-15239

Elongation of polyunsaturated fatty acids (PUFAs) to induce remyelination in multiple sclerosis. (Research)

MMultiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system (CNS), in which microglia and infiltrated macrophages play a crucial role. Chronic active demyelinating lesions observed in progressive MS are characterized by inflammatory phagocytes that enhance lesion development and halt CNS repair. Current therapies slow disease progression, yet fail to induce repair. Therefore, there is a pressing need for novel therapies for progressive MS. Driving involved phagocytes towards an anti-inflammatory, regenerative phenotype is considered a promising strategy to induce CNS repair. Our recent data show that prolonged intracellular accumulation of myelin-derived lipids induces an inflammatory phenotype in phagocytes and that enzymes of fatty acid metabolism drive the induction of this detrimental phenotype. Based on my preliminary data, I hypothesize that targeting the elongation of dietary-derived polyunsaturated fatty acids (PUFAs) induces a reparative phagocyte phenotype, promoting remyelination in MS. To test this hypothesis, I elucidate if modulating PUFA elongation induces CNS repair by utilizing state-of-the-art cell- and, tissue culture, animal models and human MS lesions, combined with innovative lipidomic techniques. Obtained results will lead to enhanced insights into MS lesion progression and repair, and identify PUFA elongation as a target for developing improved treatments for demyelinating diseases such as MS.

01 November 2024 - 31 October 2028