Project R-12271

A novel target to boost OPC maturation and remyelination in multiple sclerosis (Research)

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis (MS). Why endogenous repair mechanisms fail in these disorders is poorly understood, however, there is now strong evidence that this is related to the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. My preliminary findings indicate that a specific fatty acid transporter is a strong driver of CNS repair by promoting the differentiation of myelin-forming oligodendrocytes. I therefore hypothesize that this transporter promotes remyelination by increasing the uptake of fatty acids by OPC. By using innovative state-of-the-art techniques, transgenic mouse models, and unique human patient samples, I aim to unravel the metabolic changes that underlie the impact of this transporter on oligodendrocyte differentiation and assess if identified metabolic pathways and intermediates can be harnessed to promote CNS repair. Findings from this project will lead to increased insight in the role of this fatty acid transporter in OPC maturation and CNS repair, and will unravel the therapeutic applicability of fatty acid transporter modulators to stimulate CNS repair in demyelinating disorders such as MS.

01 November 2021 - 31 October 2023