New insights into multiple sclerosis: it's not just about the lesions

 

Image credit: https://openai.com/index/dall-e/

Multiple sclerosis (MS) is a disease that affects the brain and spinal cord, and it’s different for everyone. Scientists have been trying to understand why some people get a more severe form of MS than others. New research has made some exciting discoveries by looking at the brains of people with MS in incredible detail.

This study, led by Will Macnair and colleagues, analyzed over 600,000 individual cells from the brains of 54 people with MS and 28 people without the condition. They used a technique called single-nucleus RNA sequencing (snRNA-seq) to see what genes were active in each individual cell. This is like looking at the instruction manual of each cell to understand what it’s doing.

Key Findings

• White vs. Grey Matter: The study found that changes in brain cells are different in the white matter (the inner part of the brain with nerve fibers) and grey matter (the outer layer with nerve cells) of people with MS. This means MS affects these two parts of the brain in different ways.
• Lesion Types: The researchers looked at different types of MS lesions – areas of damage in the brain. They found that the cells within these lesions had similar gene activity patterns, suggesting that the damage is part of a global response, rather than specific to the type of lesion. This was a surprising result.
• Patient Differences: Surprisingly, the biggest differences in gene activity were found between individual patients, not between different lesion types. This means that what's going on in the brain cells of one person with MS is very different from what's happening in another person's brain, even if they both have similar lesions. This suggests that each person with MS may have their own unique way in which the disease is affecting their brain cells.
• Patient Subgroups: Using a sophisticated data analysis approach (MOFA+), the study identified four main subgroups of MS patients based on the unique patterns of gene expression in their white matter cells. These groups weren't explained by the type of lesions, sex, age or any other known factor.
• Glial Response: These subgroups appear to be driven by different responses in glial cells, which are the support cells of the brain.
• One subgroup shows a "stressed" cell response with increased activity in genes involved in protein folding and stress.
• Another subgroup had an immune response with higher levels of interferon genes.
• The other subgroups also show distinct patterns in the glial cells.
• Validation: The team validated these findings in an independent group of MS patients and also used a technique called RNAscope to visualize these different patterns in brain tissue. This provides strong evidence for their findings.

Why is this important?

This research suggests that we need to think about MS in a new way. It’s not just about the lesions; it’s about how the cells in each individual person are responding to the disease. These findings may help explain why some clinical trials for MS treatments haven't worked well for everyone. It also points the way for more personalized medicine approach for MS.

Moving Forward

The findings open up the possibility of developing new therapies that are tailored to the specific biology of each patient’s MS. The study also provides a valuable resource for other researchers, allowing for a deeper investigation of the biology of MS. This research marks a significant step forward in our understanding of MS.

This study highlights the complexity of MS and suggests that future research and treatment approaches should be more personalized, based on the unique biological profile of each patient.

 

Additional information: snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses. Neuron DOI: 10.1016/j.neuron.2024.11.016

 

Journal information: https://www.cell.com/neuron/home