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Targeting nerve fibre damage

  • Damage to nerve fibres underlies the disability seen in progressive forms of MS and at this stage is irreversible.
  • An Australian team has looked at the role of a particular protein in nerve fibre damage in laboratory models of MS.
  • For the first time, they have identified a key role for this protein in nerve fibre damage and myelin loss, paving the way for potential treatments that block this damage in MS.

Multiple sclerosis (MS) is due to the body’s own immune cells attacking the brain and spinal cord.

Usually, this attack starts with the coating around the nerve fibres, which is made of myelin. Myelin can be repaired, but this is often incomplete and once myelin is permanently lost, the underlying nerve fibres start to be damaged. Damage to the nerve fibres themselves is not able to be repaired and it is this type of damage that leads to the disability accumulation seen in progressive forms of MS.

A group of researchers including Jae Lee and Dr Steven Petratos from Monash University, who are funded by MS Research Australia and The Trish MS Research Foundation, have been looking
at the role of a particular protein in the damage to nerve fibres. In previous research, they have shown that when this protein is removed from cells, MS symptoms are less severe in laboratory models of MS. What is not clear from this earlier work however, is whether the reduced symptoms are due to the attack by immune cells on the nerve being blocked or whether there is something different about the nerve fibre that makes it less vulnerable to damage.

In their new study, published in the Journal of Neuroscience, the team used a laboratory model of MS to examine the molecular pathways related to this protein. In a series of experiments where they removed the protein from nerve cells and then added it back in, they showed that damage to the nerve fibre was linked to blockages in the transport of molecules along the nerve fibre. Nerve cells transport vital molecules related to energy production and other materials along the nerve fibre to keep the nerve cell healthy.

The results show that this protein seems to be linked to both the direct nerve fibre damage and the loss of myelin. This is the first time that experiments have shown that the nerve fibres themselves have a role to play in maintaining myelin in MS.

At the moment, medications for MS are based on blocking the attack of the immune cells on myelin and are ineffective against the nerve fibre damage seen in progressive MS. Understanding the details of how nerve fibres are damaged in MS and the molecules involved brings us one step closer to finding ways to block nerve damage in MS and ultimately provide blueprints for treatments that can reverse damage and treat progressive MS.

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Targeting nerve fibre damage