Could White Matter Give Us a Lead on a Treatment to Prevent MS Inflammation?

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Lesions are the inflammatory sites where the myelin is broken down and taken up by microglial cells. But do we see something in the tissue even before these inflammation spots appear?

To answer this question, Aletta van den Bosch and Wiebke Moebius looked into human post-mortem brains of MS patients and controls that have been donated. Their focus was particularly on the so-called ‘normal-appearing white matter’. 

The team took a detailed look at myelin to see if there are early changes in people with MS. Myelin is an insulating white, fatty substance that is wrapped up to 150 times around the nerve fibers. At regular distances from each other there are interruptions of the myelin, these are the Nodes of Ranvier. During the transmission of electrical signals, the signal jumps from one Node or Ranvier to the next, allowing a myelin-containing fiber to transmit a signal 100 times faster than without myelin. In people with MS, myelin is damaged and signal transmission in the central nervous system is disrupted. What kinds of changes in brain tissue can we observe in the early stages of MS?

‘In MS, myelin was found to be less tightly wrapped around the nerve-fiber. This means that the fiber is not properly insulated which has major consequences: the signal can’t be transmitted as fast as it used to be. We saw that where myelin was less attached to the fiber, there was a disruption of the nodes of Ranvier combined with increased levels of T-cells and activated microglia. Furthermore, there were more mitochondria. Mitochondria are the energy factories of the cell, so this phenomenon may indicate that more energy is needed for signal movement and maintenance of the fibers.’

‘The next step is to see if we can prevent the myelin from winding so loosely around nerve endings. First, we want to experiment in culture dishes to see if we can make the wrapping of myelin stronger. Subsequently, we will have to perform tests in laboratory animals, and eventually we will be able to take the step to humans. It would be great if we could find something to prevent myelin detachment. While this will not prevent the damage of the lesions that are already there, it might prevent the development of new lesions. This would provide a whole new target for MS treatment.”

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Sources:

Aletta M. R. van den Bosch, Sophie Hümmert, Anna Steyer, Torben Ruhwedel, Jörg Hamann, Joost Smolders, Klaus‐Armin Nave, Christine Stadelmann, Maarten H. P. Kole, Wiebke Möbius, Inge Huitinga. Ultrastructural Axon–Myelin Unit Alterations in Multiple Sclerosis Correlate with Inflammation. Annals of Neurology, 2023; 93 (4): 856 DOI: 10.1002/ana.26585

Netherlands Institute for Neuroscience – KNAW. “The white matter of the MS brain shows abnormalities even before inflammation.” ScienceDaily. ScienceDaily, 25 May 2023. <www.sciencedaily.com/releases/2023/05/230525141313.htm>.

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