New perspective promises potential MS breakthrough

Discovering why a critical nerve sheathing called myelin deteriorates might be key to curing multiple sclerosis, new research from Galway suggests

A RESEARCH group based in Galway have made an important discovery about multiple sclerosis, something that may lead to new drug treatments against the disease.

Dr Una FitzGerald leads the team at NUI Galway’s National Centre for Biomedical Engineering and Science where she is leader of the stroke and MS research group.

The current work is one of only two such research projects being undertaken anywhere in the world, she says.

Up to 7,000 people in Ireland have MS, a progressive neurological disease that causes damage to myelin, the protective coverings of nerve cells. If the myelin is damaged or destroyed, the nerves “short circuit” like bare electrical wire.

“The myelin sheath breaks down and causes the nerve signal to move more slowly,” says Dr FitzGerald.

Patients with MS typically have alternating periods of disease symptoms and then remission, but as it advances to secondary progressive MS, the symptoms are there all of the time, she explains. Her research focus is on this secondary state and she is trying to understand why this happens.

MS research activity has tended to focus on the brain’s white matter, a region of tightly packed myelin-covered nerves. This is because the damage caused by the disease is most obvious in this tissue, she says.

The team, which includes senior post-doctoral researcher Dr Jill McMahon in the Galway lab, Dr Stephen McQuaid from Queen’s University Belfast and Prof Richard Reynolds of Imperial College London, decided to take a different approach.

They studied damage caused to nerves in the brain’s grey matter, the processing part of the brain that controls thought, movement and the senses.

“These lesions [grey matter damage] are there all of the time throughout the disease,” says Dr FitzGerald, but are much more difficult to see. The team had to use specialised methods to detect the damage and understand what was driving it.

Their belief is that damage to the grey matter was the main cause of the severe symptoms seen in secondary progressive MS.

With funding from MS Ireland and private donations via the Galway University Foundation they went after the cause, focusing on a cell-signalling system known as the ER-stress pathway.

The ER-stress pathway is triggered when a cell is under some kind of assault. In a stroke this happens when cells become starved of oxygen. In MS it happens when the disease affects a compartment within the cell where the ingredients for myelin are produced, Dr FitzGerald explains.

The researchers used MS brain samples from tissue banks in Dublin and Belfast, cutting slices just 100th of a millimetre thick for analysis.

Using their advanced methods, the team was able to show that levels of ER-stress were raised in areas of myelin damage in both white and grey matter.

“We believe we have shown the pathway is relevant to MS,” she says.

Dr FitzGerald believes that substances released by the cells when the ER-stress pathway is switched on are actually causing the damage to myelin.

More research is needed to prove the connection, but the finding opens up the possibility of developing drugs that can block or interfere with the pathway, she says.

The hope is that the drug would switch off the pathway and shut down the myelin damage.

The next step is to develop a model system so that the pathway can be studied in more detail. Understanding myelin damage was “essential to find ways to treat, prevent or one day cure MS”, says the chair of MS Ireland’s research committee, Prof Michael Hutchinson of St Vincent’s Hospital. He expressed MS Ireland’s “delight” in funding such an important piece of research.

MS Ireland is currently taking applications for its 2011 research programme and is also introducing a Dean Medal travel bursary. Information about the programme is available at ms-society.ie/pages/research