NDST1 is upregulated in multiple sclerosis (MS) and positively correlates with remyelination potential and small lesion size

1. MRC Centre for Regenerative Medicine, Multiple Sclerosis Society Centre for Translational Research, University of Edinburgh, Edinburgh, UK
2. Aix Marseille Univ, CNRS, IBDM, Marseille, FranceAix

NDST1 is an enzyme performing the first and rate limiting step of heparan sulfate (HS) production. Heparan sulfate has been shown to be involved in oligodendrocyte precursor cell (OPC) migration and proliferation. In a mouse model of CNS demyelination, our collaborators have shown that NDST1 and HS are upregulated in oligodendroglial cells and deletion of NDST1 in OPCs negatively impacts remyelination and namely increases lesion size.

We aimed to assess the relevance of NDST1 in the human demyelinating disease multiple sclerosis (MS), where therapies are being sought to improve remyelination and reduce disability. We examined the NDST1 expression patterns in post-mortem human MS and control brain tissue. We found that NDST1 is upregulated in the normal appearing white matter (NAWM) and in lesions of MS tissue compared with white matter of control tissue. The primary cell type expressing NDST1+ cells was oligodendroglial cells (OLIG2+), followed by astrocytes (GFAP+), macrophages/microglia (IBA1+) and neurones (NEUN+). Chronic inactive lesions, which are least likely to repair, have significantly less OLIG2+ NDST1+ cells than NAWM. Patients who have more NDST1+ cells have higher remyelination potential (judged on a scoring system of how likely the lesion types they have are to remyelinate). Moreover, higher numbers of NDST1+ OLIG2+ cells inversely correlate with lesion size – the higher the number, the smaller the lesion.

We suggest that in MS, NDST1 is upregulated primarily in oligodendroglial cells and that the level of upregulation is positively correlated to the remyelination potential.  This provides another potential target for therapies to improve remyelination.

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* entered into the PhD student poster competition