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Multiple Sclerosis: The cellular basis of myelin repair

LMU and TUM scientists investigate, which cells can repair myelin sheaths in the inflamed brain.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system and the most common neurological cause for persistent disability in young adults. In MS, immune cells enter the brain and spinal cord where they damage nerve cells and their isolation, the so-called myelin sheaths. Damaged myelin sheaths can in principle be repaired by a process called remyelination – however, this often fails in patients with MS.

In a collaborative study, the teams of Martin Kerschensteiner from the Biomedical Center and Thomas Misgeld from the Institute of Neuronal Cell Biology, TU Munich, have used a mouse model for MS to resolve which cells can contribute to remyelination. They had shown before that oligodendrocytes, the myelin-generating cells in the central nervous system, can survive the inflammatory insult in an “amputated” state.

In the new study the researchers wanted to understand, if and how such surviving, amputated cells could contribute to myelin repair. The scientists established genetic tagging strategies allowing them to selectively label either surviving or newly differentiating oligodendrocytes. Using in vivo microscopy, the Kerschensteiner and Misgeld teams showed that surviving oligodendrocytes can in fact form new myelin sheaths. However, in inflammatory lesions this process is often inefficient - in particular when compared to myelin formation by newly differentiating oligodendrocytes.

This finding suggests that surviving oligodendrocyte would need therapeutic support to efficiently repair myelin. Notably, the researchers found that current therapeutic strategies developed to support myelin formation by newly differentiating oligodendrocytes rather blocked than supported myelin repair by surviving oligodendrocytes.

Taken together, this study indicates that new therapeutic strategies are required to promote myelin formation by surviving oligodendrocytes in MS.

Publication: Mezydlo et al.: Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex, Neuron 2023