MS is a neurodegenerative, inflammatory disease of the central nervous system, in which myelin, the insulating layer surrounding axons is damaged, resulting in a plethora of heterogeneous symptoms that progress over time. The clinical symptoms and disease course are variable, but also at the sites of damage, lesions, there is considerable heterogeneity in the molecular processes and cell types involved. Different MS lesions types are classified based on inflammation and myelin loss. The research team headed by Bart Eggen, Susanne Kooistra and Wia Baron exploited spatial transcriptomics to explore MS lesion heterogeneity and progression.
Through spatial transcriptomics, which allows for the detection of gene activity in a tissue section, changes in biological pathways were identified that are restricted to different lesions and areas within lesions. A transcriptionally distinct rim was detected around active lesions, which is of importance as the rim is considered an area critically involved in MS lesion expansion.
With computational methods, we predicted MS lesion evolution based on the spatial gene expression data of diseased and healthy white matter areas. Biological trajectories were identified that may explain the progression between different lesion types. This data predict that lesion rims precede lesion core formation, and implicate lesion rims as an area of both lesion expansion or repair.
These findings provide insight in the processes that are involved in the formation and expansion of MS lesions. This insight can help future endeavors towards identifying novel therapeutic targets that target lesion expansion, prevent the progression to a lesion core with permanent damage, and stimulate the regeneration of myelin.
This work was financially supported by the Stichting MS Research.
Publication: Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis
