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GMSI Award 2015 – Driving microglia metabolism towards remyelination and restoration of brain damage in multiple sclerosis

Claudia Verderio

ECTRIMS_Ceremony_06_Claudia_Verderio

This lecture was given at the Grant for Multiple Sclerosis Innovation Awards Event, 8th October 2015. The GMSI award was supported by Merck KGaA, Darmstadt, Germany. Dr. Verderio is an award winner and works at the National Research Council, Milan, Italy.

According to Dr. Verderio, the new proposal stemmed from data on the biological activity of vesicles from microglia cells, on the proliferation, differentiation and myelination of oligodendrocyte precursor cells (OPCs). These were mainly present in the healthy brain in a quiescent state. Upon injury they started to proliferate; they differentiated into true oligodendrocytes, which quite efficiently supported remyelination. However, there was a general remyelination failure in the chronic progressive phase of multiple sclerosis. This was probably due to a unfavourable local inflammatory environment.   

Dr. Verderio and her colleagues had studied the effect on OPCs of vesicles produced by microglia, either unstimulated or M1 microglia (TH1 cytokines; pro-inflammatory)) or M2 microglia (anti-inflammatory; IL-4). Vesicles induced by proinflammatory M1 microglia significantly reduced the differentiation rate of OPC. This was counteracted by coculture with MSC. Thus MSC resurrected the beneficial function of microglia. 

The first objective of the project was to validate the promyelinating action of extracellular vesicles released from microglia conditioned with MSC in the lysolecithin mouse model of focal demyelination. The second objective was to dissect the metabolic changes induced in microglia by exposure to MSC. The third objective was to investigate the effects of metabolically reprogrammed microglia on in vivo remyelination. This might be a new approach to induce the M1-M2 microglia transition.