In the progressive stage of multiple sclerosis repair of damaged myelin fails. Myelin is the insulating layer surrounding axons that is crucial for communication between nerve cells. The lack of remyelination is due to the fact that a specific cell type in the brain called oligodendrocyte precursor cells (OPCs) no longer differentiate into mature myelinating cells. Previous research has already shown that lipids play an important role in this differentiation process. Lipids are taken up by oligodendrocytes by lipid transporters such as CD36. In this project we investigate the impact of CD36 on oligodendrocyte differentiation and determine whether this knowledge can be used for therapeutic purposes.   

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis (MS).  Why endogenous repair mechanisms fail in MS is poorly understood. However, there is now strong evidence that this is related to the inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Our preliminary findings indicate that the fatty acid transporter CD36 is a strong driver of CNS repair by promoting the differentiation of myelin-forming oligodendrocytes. This project will use innovative techniques, transgenic mouse models and unique patient samples to identify the impact of this fatty acid transporter on metabolic changes during oligodendrocyte differentiation and investigate whether these identified mechanisms can be used to promote CNS repair. The results of this study will provide further insight into the role of this fatty acid transporter in OPC differentiation and CNS repair and the therapeutic applicability of fatty acid transporter modulators in demyelinating diseases such as MS.