Scientists explore how to repair MS damage

Behind the Headlines

Monday December 6 2010

Brain scan showing MS damage (red/yellow) due to myelin loss

Scientists have announced a "revolutionary" discovery that could reverse the nerve damage and paralysis caused by multiple sclerosis, reported the Daily Express.

The news story is based on a laboratory study in animal and human cells. The study established the role of particular substances in the natural repair of myelin, the substance that insulates nerve cells in the brain and that is damaged in multiple sclerosis (MS).

This type of research is a crucial first step in understanding the neurological processes underlying diseases such as multiple sclerosis. The findings have been called “one of the most exciting developments in recent years” by the Multiple Sclerosis Society, which part-funded the research.

These are preliminary findings, however, and this should be emphasised. Whether the processes identified here in rat cells will translate directly into human cells remains to be seen. As the lead researcher, Prof Robin Franklin, says: "The caveat is that the road from where we are to a treatment is unpredictable, but at least we now have a road to go down". The Guardian reports him as saying there could be “preliminary trials of potential drugs within five years and treatments within 15 years”. 

 

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, the Queen’s Medical Research Institute in Edinburgh and other European and international academic organisations. The research was published in the peer-reviewed scientific journal Nature Neuroscience.

Many of the newspapers reporting this study only mention that this research was in rodents towards the end of their articles.

 

What kind of research was this?

This research examined how myelin, a protective covering that surrounds nerve fibres in the brain and spinal cord, is repaired naturally in the body. Myelin is the electrically insulating sheath that protects the cells of the central nervous system and allows electrical signals to be transmitted smoothly. In healthy bodies, damaged myelin is repaired by cells called oligodendrocytes. In people with demyelinating diseases such as multiple sclerosis (MS), however, the myelin does not repair.

This animal and laboratory research investigated the processes that lie behind ‘remyelination’ of cells in the central nervous system in rats and in post-mortem samples of cells from the brains of people with MS. The researchers were particularly interested in what signals the oligodendrocytes respond to once demyelination has occurred (i.e. what ‘recruits’ them).

 

What did the research involve?

The researchers induced demyelination in rats using a toxin and analysed in detail the lesions that resulted in the rats’ brains. They used these observations to make a map of the genetic processes that occur in nerve cells as they respond to myelin damage. Each stage of the response was recorded and analysed with the aim of furthering the understanding of the way that the body spontaneously regenerates myelin.

The researchers isolated the lesions in the rats’ brains that developed 5, 14 and 28 days after exposure to the demyelinating toxin. They then identified which genes were being expressed in the lesions over time, and explored their function and how they were involved in processes leading up to remyelination.

There are several cells involved in the remyelination process, including oligodendrocytes, microglia or macrophages, and reactive astrocytes. The researchers wanted to identify exactly which of these cells was expressing the genes of interest. Further studies were conducted to determine exactly which kinds of oligodendrocytes were recruited to help repair damaged myelin. This involved using genetically modified animals that could not produce key substances that were important in the remyelination process.

Similar experiments were conducted on cell samples from three humans who had died with MS. Here, the researchers were looking for evidence of expression of the same genes they had identified in the animal experiments.

 

What were the basic results?

The researchers identified several stages of the process of “spontaneous remyelination” of cells. One major finding was that oligodendrocytes appear to be signalled to action initially by messages sent from cells in the damaged area. These are then followed by remyelination signals inspired by a second genetic location.

The researchers identified several genes that seemed to be active in the remyelination process, the most active of which is called retinoid X receptor gamma. They also established that these genes were being expressed mainly in the damaged regions of the brain, and that the processes involved cells called macrophages and oligodendrocytes. They also established that the retinoid X receptor gamma gene stimulates stem cell precursor cells to develop into oligodendrocytes that are able to help repair the myelin.

In human tissue, the retinoid X receptor gamma gene was more active in the plaque tissue than in the normal brain tissue.

 

How did the researchers interpret the results?

The researchers conclude that they have profiled the complex genes and reactions involved in remyelination of healthy cells and have, as a consequence, generated a "transcriptional database of genes that are differentially expressed in association with spontaneous CNS remyelination". They say that this will be a useful resource for furthering our understanding of what causes precursor cells to activate and repair damaged brain cells.

They conclude that they have identified a particular role for the retinoid X receptors and that this "opens a new area of research on the role" of these substances in the repair and regeneration of cells.

 

Conclusion

This type of research is a crucial first step in understanding the neurological processes that lie behind diseases such as multiple sclerosis. The findings have been called “one of the most exciting developments in recent years” by the Multiple Sclerosis Society, which part-funded the research.

Emphasis needs to be placed on the preliminary nature of these findings, however. The MS Trust called this an “important area of MS research”, but also added that this is still early research in rodents. Whether the processes identified here in rat cells will translate directly into human cells remains to be seen.

The researchers say that the process by which retinoid X receptor gamma is activated in rats is probably the same in humans. If the processes are the same, there will be years of development and testing to create a treatment that can simulate or stimulate the regenerative mechanisms that the researchers recorded and analysed in these rodents.

As the lead researcher, Prof Robin Franklin, says: "The caveat is that the road from where we are to a treatment is unpredictable, but at least we now have a road to go down". The Guardian reports him as saying there could be “preliminary trials of potential drugs within five years and treatments within 15 years”.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Breakthrough gives new hope over MS. Daily Express, December 6 2010

MS could be reversed by activating stem cells in brain, new study suggests. The Guardian, December 6 2010

Study offers hope of 'repairing' MS. BBC News, December 6 2001

Stem cell finding could reverse ravages of multiple sclerosis. Daily Mail, December 6 2010

Breakthrough could lead to MS drug. The Independent, December 6 2010

Links to the science

Huang JK, Jarjour AA, Oumesmar BN, et al. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nature Neuroscience 2010, Advance online publication December 5

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