Myelin Repair: Cellular Switch Identified?

PROGRESSIVE MULTIPLE SCLEROSIS AND MYELIN REPAIR

We have seen an increasing number of powerful new treatments developed recently for relapsing remitting multiple sclerosis.  These treatments work in various ways to try and stop the immune attack, although we are yet to develop therapies that can improve myelin repair.  As well as this, our understanding of progressive multiple sclerosis is still somewhat lagging behind, and as such, so are the treatment options.  Therefore, any research that identifies potential ways that progressive multiple sclerosis can be slowed and opens up avenues for myelin repair should be highlighted and promoted.

WHO?

A team of researchers primarily from the Achucarro Basque Center for Neurosciences at the University of the Basque Country in Spain.

WHAT?

The study aimed to provide a better understanding of how certain cells in the brain can be switched to reduce inflammation and promote myelin repair.  It was published in the journal EMBO Molecular Medicine and can be accessed here.

HOW?

This research involved using mice with an animal model of multiple sclerosis, known as experimental autoimmune encephalomyelitis or EAE.  If you want to know more about EAE, a short summary of what it is and how it is used in multiple sclerosis research can be found here.

FACT #1:  Microglia are types of immune cells that form part of the immune defence in the central nervous system (CNS).

FACT #2:  Microglia can be both pro-inflammatory and anti-inflammatory.  These pro-inflammatory microglia are associated with damage to the nerves (particularly during the progressive phase of the disease), whereas the anti-inflammatory forms work to protect against further attack and promote repair of the myelin.

FACT #3:  It has been suggested that a block in switching between pro-inflammatory and anti-inflammatory microglia plays an important role in the lack of repair in chronic lesions in multiple sclerosis.

FINDING #1:  The researchers identified the “switch” on these microglia cells in the form of a receptor known as P2X4R.

FINDING #2:  Turning on this switch resulted in microglia being shifted towards becoming anti-inflammatory.  Doing this led to reduced symptoms in the EAE mouse model of multiple sclerosis.

FINDING #3:  Turning off or blocking this switch resulted in microglia becoming pro-inflammatory.  Doing this led to a worsening of disease and symptoms in the EAE mouse model of multiple sclerosis.

FINDING #4:  The switch didn’t appear to have an impact on the acute phase of the disease, as is to be expected with these cells being linked to the progressive course of multiple sclerosis.

FINDING #5:  Turning on the switch to favour the anti-inflammatory microglia was important for these cells to be able to swallow up and remove myelin debris.  Their increased ability to eliminate the remnants of the damaged myelin led to improved myelin repair by other cells, known as oligodendrocytes.

THOUGHT:  This research represents an exciting development in our understanding of how important cells can be switched between states that are either damaging or helpful in multiple sclerosis.

THOUGHT:  This is at a very early stage and the results have been mostly generated from experiments performed in a mouse model of multiple sclerosis.  It is unclear whether these results will translate across to human studies.

THOUGHT:  If it turns out that this does work the same in multiple sclerosis in humans, it may lead to new avenues for treatment that can reduce damage during the progressive form of the disease and promote the repair of already damaged myelin.