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Brain cell changes in people with MS revealed

24 January 2019

Fresh insights into the types of cells found in the brains of people with multiple sclerosis could help develop improved therapies, new research published in Nature has found.

The study focused on cells in the brain that help to repair damage to nerve cells caused by the disease. The researchers identified various types of these cells – called oligodendrocytes. They found people with MS have different types of oligodendrocytes than healthy people.

The findings could shed new light on how the disease progresses and could also help scientists develop treatments.

In collaboration with the Karolinska Institute in Sweden the team analysed post-mortem brain samples from five people without neurological disease and four people with the most advanced form of multiple sclerosis, called progressive MS.

Working with researchers from the healthcare company Hoffmann-La Roche, they used an advanced genetic analysis technique called single nuclear RNA-Seq. This technique provides a snapshot of all the genes that have been switched on in a single brain cell, providing insights into how each individual cell functions. By doing this on thousands of brain cells, the approach can build a detailed picture of all the cell types that are present in the brain from that person.

The researchers found there are several types of oligodendrocytes, and that the ratio of these cells in people with MS differs from healthy people. These differences suggest the oligodendrocytes are functioning differently in the brains of people with MS, which might be key to understanding how disease progresses, the researchers say.

Professor Charles ffrench-Constant said,

"We found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain."

MS occurs when the protective sheath that surrounds nerve cells – called myelin – becomes damaged. This means that nerve cells cannot transmit signals around the body as effectively. It also leaves nerve cells vulnerable to damage, and eventually the nerves can die.

Oligodendrocytes are found in the brain and spinal cord where they repair damaged myelin. In people with MS, this process does not work as well as in healthy people. Many treatments under development for MS are designed to target oligodendrocytes in the hope of boosting myelin repair. Professor Anna Williams, who helped lead the study, said,

"Understanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximising the chances of developing treatments."

Studies with mice had previously identified several types of oligodendrocytes in the mouse brain, suggesting each have slightly different functions. This is the first study to show that people also have several types of oligodendrocytes in the brain. The differences in types of oligodendrocytes they found in people with MS might explain why their myelin repair process does not work as well. The study also found people have and different types of oligodendrocytes than mice. The findings suggest the cells may work differently in each species. This could have important implications for how findings from mouse studies of MS are interpreted.

Multiple sclerosis is a lifelong condition that causes balance problems, fatigue and progressive disability. Around 2.5 million people are living with the condition worldwide. There are currently no treatments for the progressive form of the disease. Dr Susan Kohlhaas Director of Research, MS Society said,

"More than 100,000 people in the UK have MS, and many of them are still without effective treatments. Those living with progressive forms of MS desperately need new options that repair myelin damage and halt progression."

The study, published in Nature, was funded by the UK MS Society, the European Union and the European Research Council. The European Committee for Treatment and Research of Multiple Sclerosis and the Wellcome Trust also funded the research, among others.

Jäkel et al. (2019). Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature, published online 23 January 2019. DOI: https://doi.org/10.1038/s41586-019-0903-2

Oligodendrocytes are different in MS brain compared to Control brain

The image above shows that oligodendrocytes are different in MS brain compared to Control (Ctr) brain. Each dot represents a single oligodendrocyte and the most similar cells are grouped together, and then colour coded. There are fewer oligodendrocyte types 1 and 6, but more of oligodendrocyte types 2, 3 and 5 in MS brain compared to controls. These differences suggest that oligodendrocytes work differently in MS brain and normal brain.

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