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Text by Ian Fyfe for 'Nature Reviews Neurology'

Molecular pathways involved in early neurodegeneration in progressive multiple sclerosis (MS) have been identified with a novel tissue analysis technique. The work, published in Nature Neuroscience, identifies potential therapeutic targets.

Neurodegeneration underlies progression in MS, but incomplete understanding of the mechanisms involved is hampering development of effective therapies. In their new work, Lars Fugger and colleagues used spatial transcriptomics to gain insight into the specific pathways involved.

'Spatial transcriptomics is a novel technique that can detect the expression of thousands of genes with spatial resolution directly in the tissue,' explains Fugger. 'Thus, it becomes possible to combine the structural detail of microscopy with high-dimensional measurements to capture complex disease pathways.'

The researchers studied post-mortem tissue from 13 patients with progressive MS and five controls. They first mapped areas of neurodegeneration in the grey matter and identified regions at different stages of degeneration. They then analysed changes in gene and protein expression in these areas to determine which molecular pathways are associated with different stages.

'By measuring gene expression and localization in the tissue simultaneously, we were able to identify receptor–ligand pairs in close proximity to one another in specific stages of MS neurodegeneration in the brain, suggesting that the corresponding signalling could be involved in the disease,' explains Fugger.

Crucially, the approach identified pathways involved in early neurodegeneration, when treatment is most likely to be beneficial. These pathways, therefore, represent candidates for therapeutic targeting.

Read the full paper in Nature Neuroscience.

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