Abstract
Charcot-Marie-Tooth disease (CMT1A) is the most common hereditary neuropathy, caused by a PMP22 gene duplication, leading to myelin defects and slow nerve conduction. Despite advances in targeting PMP22, no effective treatment exists for CMT1A patients. Increasing evidence indicates that the immune system, and especially macrophages, plays a secondary role in the pathology, but this is far from understood. Macrophages are considered to be one of the most plastic cells of the immune system, and they have the capacity to profoundly adapt to their tissue of residence and to change in response to injury or disease. By using state-of-the-art transcriptomics and lipidomic approaches, advanced microscopy, metabolism assays, preclinical models, and unique human CMT1A patient nerve biopsies, I here aim to phenotype the metabolic and functional properties of macrophages in CMT1A, and explore how they influence Schwann cell differentiation and myelination. The findings of this study will provide deeper insight into the role of macrophages in CMT1A disease pathology and uncover novel immuno- and lipid metabolism-based strategies to enhance recovery and promote remyelination in CMT1A.
Researcher(s)
Research team(s)
Project type(s)