Bulletin

Issue: July 2004

Research

Research suggests new ways of treating MS

Researchers from La Trobe University have established a link between a multiple sclerosis (MS)-like condition in mice and damage to the nerves of the spinal cord. The work opens up a range of possibilities for treating MS using a growing number of new techniques for repairing spinal cord injury.

In a paper recently published in Nature Neuroscience, a team led by La Trobe Research Fellow, Dr Tara Karnezis, showed that the onset of the MS-like condition in mice can be significantly delayed by inhibiting or removing a protein which normally prevents spinal nerve regeneration. There is even a suggestion that the protein, known as Nogo A, may have a hand in initiating MS.

'The novelty of the work is that until now no one thought of applying the knowledge that has been gained from the huge amount of recent work on spinal cord injury to MS,' said the Director of La Trobe's Neuroimmunology Laboratory in the School of Molecular Sciences, Professor Claude Bernard, who supervised the research project.

MS is a degenerative disease of the nerves of the spinal cord and brain that, since the eradication of polio, has become the most common cause of paralysis in Western countries. It generally strikes people between the ages of 20 and 40 and is more common in women than men.

Until recently, MS was thought to be solely associated with inflammation of the fatty (myelin) sheath which surrounds the spinal nerves. Degeneration of this sheath results in a misfiring of nerve impulses along the spinal cord. But, following recent work at La Trobe University and in the US, an increasing number of neuroscientists now believe MS also involves actual damage to the nerves themselves. And Nogo A inhibits regeneration of these nerves.

The researchers interfered with the functioning of Nogo A before inducing the condition known as experimental autoimmune encephalomyelitis (EAE) - used as a model of MS - in mice. In one set of experiments they vaccinated against Nogo A, by injecting an active section of the protein to prime the immune system against it. The vaccination resulted in a significant delay in the onset of EAE and a reduction in the severity of its clinical symptoms. The team also worked at triggering EAE in which the gene for producing Nogo A was missing - with much the same outcome.

Nogo A is produced in the myelin sheath, but acts on the spinal nerves themselves. It has been specifically implicated in preventing regeneration. So the research team's results suggest that by neutralising Nogo A, damage to these nerves has somehow been able to be repaired or maybe even have been prevented in the first place. Whatever the case, the work points to a direct functional connection between EAE and spinal nerve damage.

Until now, much of the work linking MS with nerve damage has been undertaken on tissue from human autopsies, Professor Bernard said. The La Trobe research is the first to track the progress of the disease, and its association with nerve damage, in and experimental models of MS, thus supporting and extending the earlier US research.

'This work is important because its relevance is not limited to neuro-degenerative diseases such as MS,' Professor Bernard said. 'It also has significance for many other diseases of the central nervous system where nerves are damaged or lost.'

And there is a potential clinical spinoff. Over the past decade there has been an upsurge in research into spinal cord injury and its treatment, partly stimulated by the activism of and surrounding the star of the Superman films, Christopher Reeve, who was left a quadriplegic by a horse riding accident in 1995. This work has thrown up several new leads for treating spinal injury, which now also may be worth investigating for their relevance to MS.

Some of this research relates to useful drugs. There has been recent interest, for instance, in the role of high concentrations of the amino acid glutamate in damaging nerve cells. Researchers have been testing drugs which counteract the impact of glutamate, and have already shown they can lessen paralysis and nerve damage in mice. There also have been positive steps in using stem cells to regenerate spinal nerves.

The La Trobe group will be continuing its work investigating the possibilities of countering regeneration inhibitors like Nogo A, which may also produce useful therapy in the long term. But the immediate next step is to try and track down the site of any spinal cord injury caused by EAE in mice. Dr Karnezis is now working at Stanford University in California. •

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