MS research project at UCD yields some surprising results


By taking a different approach, researchers have discovered what could eventually be a new type of treatment, writes CLAIRE O'CONNELL

SOMETIMES IN scientific research, taking a new angle can unearth unexpected but welcome discoveries. And that’s what happened when researchers in University College Dublin’s Conway Institute looked at a type of tissue damage associated with multiple sclerosis.

It’s early days yet, but by analysing the effects of a cognition-enhancing agent on nerve cells in the lab, they have identified what could eventually offer a new approach to help address the condition.

In MS, a progressive neurologic condition that affects more than 7,000 people in Ireland, it’s thought the immune system attacks an insulating, fatty sheath around nerve cells called myelin, explains researcher Dr Mark Pickering, a post-doc at UCD’s school of biomolecular and biomedical science.

When myelin is damaged, the nerves can no longer work properly, and therapies try to protect the remaining, intact myelin rather than targeting the myelin which has already been damaged, according to Pickering.

“So far, drugs that have been used to treat MS are looking at preventing the immune damage to myelin,” he says.

In his own studies, Pickering was looking at links between damage to myelin and cognition, or the ability of the brain to function in learning. And while working with a type of drug that can enhance cognition, he discovered that it also had a welcome talent for prompting the repair of damaged myelin in cells growing in the lab.

“The project wasn’t initially to look at the myelin itself, it was to look at cognition, a secondary effect of the loss of myelin,” he recalls. “But we found that treatment with this drug accelerated the repair of myelin.”

The work, which was funded by the MS Society of Ireland, used neurons or nerve cells growing in a dish.

Pickering treated the neurons with a toxin that damages the myelin surrounding the neurons, and then he looked at the effects of adding this cognition-enhancing drug.

Neurons without the added drug repaired the myelin slowly over several days, but if the drug was added the myelin repair was dramatically faster, says fellow researcher Dr Keith Murphy, a principle investigator at the neurotherapeutics research group in UCD.

“At 24 hours after the toxin was removed, the myelin around the neurons is still very depleted in the normal situation, whereas if you had added the cognition-enhancing drug the myelin is completely normal at that point,” he explains.

“The amount of myelin left after the toxin alone would be 20 per cent of healthy levels, but with the drug on board it is back up to normal.” The cognition-enhancing drug also appears to accelerate myelin repair in other pre-clinical models where myelin has been damaged, according to the researchers.

So to build on their initial findings, the team now has funding from Enterprise Ireland and the Congressionally Directed Medical Research Programs in the US to take the project further.

They plan to do more pre-clinical studies with the drug, and then progress to the first human trials, according to Murphy.

“We are hoping that we will be ready to start to think about clinical trials within a two-year period if the data keep looking positive,” he says.

And ultimately, if all goes to plan, how would they see a myelin-repair agent being used?

“To put it into its disease context, the most usual form of MS is the relapsing-remitting version, where there are periods of inflammation causing the damage, then the inflammation dies down and there’s a period of repair of the myelin. The symptoms more or less resolve themselves in the remission period,” says Murphy.

He describes how a drug treatment to boost myelin repair could theoretically be used during those times of remission, to help tackle the damage caused during the relapsing, inflammatory periods.

“Current treatments for MS elongate the periods of remission – so you could use those drugs to buy the time, elongate the remission period, and at the same time use a myelin repair-boosting agent to make sure that the damage doesn’t progressively get worse over time.”

The researchers are keen not to raise false hopes, but they are optimistic that because the drug has previously been proven safe in humans, and because it could be trialled within the context of existing treatments for MS, they should know within about five years whether the approach can help.

The drug’s effect on myelin was something they hadn’t suspected at the start, but which they welcomed when they found it, says Murphy.