Scots researchers lead drive for new generation of Multiple Sclerosis drug – Herald Scotland

RESEARCHERS in Scotland are leading the drive to develop a new generation of multiple sclerosis drugs designed to reverse symptoms in patients with more advanced disability.

The only MS drugs currently available treat the earlier, inflammatory stages of the disease and cannot repair the nerve damage which causes problems with speech and mobility.

However, scientists in Edinburgh and Glasgow are now leading projects funded by MS Society Scotland which they hope will eventually produce treatments which can repair myelin - the protective sheath around nerve cells which is destroyed in MS.

Dr Anna Williams, a neurologist at Edinburgh University's Centre for Regenerative Medicine, said: "Myelin is like the insulation on wires - it's there to make your nerves conduct electricity better. If it comes off, your nerves don't conduct electricity well so you might want to move your leg but find it more difficult to do so because the electrical impulse isn't being transmitted properly from the brain to the muscle. In the longer term if the myelin isn't there then the nerve itself dies and people get stuck with disability.

"What we want to do is persuade the brain to put the myelin back on these nerves and stop them from dying."

The three-year project is focused on a protein called fractalkine which appears to guide repairs in the brain by first attracting macrophage cells to damaged areas to "hoover up the mess" and then instructs oligodendrocytes - the cells which carry out myelin repair - to get to work.

The scientists will analyse samples of brain tissue donated by deceased MS patients to test their theory.

"If one lesion has a lot of fractalkine then we would expect to find a lot of 'repair cells' as well, and ones that ones with less fractalkine would have fewer," said Dr Williams. "If so, that will give us an indication of whether fractalkine is important in humans."

The scientists will then attempt to use fractalkine to repair myelin in mice brains designed to simulate MS. Although fractalkine occurs naturally in humans and there is evidence that some myelin repair already takes place, it always stalls before the repair is complete. The scientists hope that by gaining a better understanding of the protein, they will eventually pave the way to a drug which can either mimic the effect of fractalkine or encourage it to work more effectively - thereby promoting myelin repair and preventing nerve cell death, a major breakthrough for MS patients.

Meanwhile, researchers in Glasgow, Liverpool and Munich are looking at how a chemical better known for its blood thinning properties could also offer clues to myelin repair.

The study is using heparin - a type of sugar normally associated with breaking down clots - but which has been modified instead to block a type of scarring response associated with MS and other nervous system damage, including spinal cord injuries. The team found that when these modified heparins were added to cell cultures in the lab designed to mimic MS, they encouraged myelin repair.

The next phase will test the response directly in mice which have been fed cuprizone, a toxin which will trigger the destruction of myelin in the rodents' brains. Once this has been achieved, the modified heparin will be administered to the mice either by an IV drip or directly by injections into the affected regions of the brain.

Afterwards the tissue will be dissected to assess whether the myelin has been restored.

Sue Barnett, professor of cellular neuroscience at Glasgow University, said: "If we can keep nerves in MS patients myelinated for longer then it might have some consequence on the progression of the disease. It could alleviate symptoms."

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Scots researchers lead drive for new generation of Multiple Sclerosis drug - Herald Scotland