SCIENTISTS researching cures for multiple sclerosis have proven for the first time that it is possible to repair damaged nerve tissue in humans.

A study due to be presented tomorrow at MSVirtual2020, a joint meeting of the European and American Committees for Treatment and Research in Multiple Sclerosis, found that a cancer drug normally used to treat lymphoma is capable of repairing damage to myelin.

Researchers say this is a "critical" breakthrough which could pave the way to therapies to halt and reverse MS damage.

A clinical trial involving 52 patients with relapsing MS, funded by the MS Society, compared outcomes of cancer drug called bexarotene against a placebo.

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They found that bexarotene helped to restore myelin – the protective fatty coating that surrounds nerve fibres which is attacked and destroyed in MS by the body's own immune system. 

This damage is what stops signals getting around the body, leading to disability and difficulties talking, eating and thinking.

The scientists used a form of MRI brain scan to identify in minute detail the patches inflammation - or lesions - caused by MS. 

When they re-examined patients' brains using the same technology six months later they were able demonstrate improvement in those who were on bexarotene, compared to the placebo. 

"That can only be caused by re-myelination, because in the brain nerve cells don't regrow," said Professor Alasdair Coles, the neurologist who led the research at Cambridge University.

Separately, the researchers also compared how fast electrical signals travelled along the optic nerve from the retina at the back of the eye to the visual cortex in the brain.

Damage to the optic nerve is common in MS patients due to the erosion of myelin, which is responsible for speeding up the conduction of electrical signals. 

The researchers found that participants who had received bexarotene saw an acceleration in the speed of these impulses after six months on the drug.

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Unfortunately, the cancer drug also caused serious side effects in many of the participants, including hypothyroidism - which leads to weight gain and depression - as well as potentially dangerous build ups of triglyceride fatty molecules in the blood, which increases the risk of strokes, heart attacks and acute pancreatitis.

As a result, it is too unsafe to be considered as a potential treatment for MS, but the evidence of myelin repair has given scientists hope that the effects can be successfully replicated using a different drug.

Researchers have already demonstrated that diabetes drug metformin can restore myelin in rats, and the medication is now set to be investigated in human trials.

Prof Coles said: "The lessons we’ve learned are incredibly exciting, as we now have further concrete evidence that re-myelination in humans is possible.

"This discovery gives us confidence that we will stop MS, and will swiftly be taken forward into further studies trialling other potential new myelin repair treatments.”

Co-investigator Professor Siddharthan Chandran from Edinburgh University, added: “We now understand much more about myelin repair and are in a significantly better position to measure re-myelination in clinical trials.”

The MS Society is now funding the trial of metformin in combination with clemastine - an over-the-counter allergy drug which was was shown in a California study to modestlimprove vision in MS patients with optic nerve damage.

It is hoped that these could provide a safer, and potentially more effective, way of stopping disability progression in the condition.

The Phase 2a clinical trial of metformin and clemastine, which has been delayed due to the Covid pandemic, will be led by Professor Coles.

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He hopes to be able to begin recruitment soon with the trial expected to take one year to complete, meaning results could be available before the end of 2021.

Prof Coles said: "What metformin seems to do is rejuvenate the stem cells that make myelin in the brain.

"If you go back to the science that bexarotene emerged from, the original observation is that older rats will not re-myelinate naturally whereas younger rats will - you don't need any drugs.

"The problem is that the stem cells that produce myelin age and become less efficient, and bexarotene wakes them up and makes them re-myelinate.

"But metformin also wakes them up and makes them sensitive to other drugs that they previously were not sensitive to.

"Clemastine, in animals, when you give it with metformin it has a much more dramatic effect.

"Our hope is that by giving metformin [to patients] we will rejuvenate the stem cells in the brain so we should see re-myelination not only at the levels we're seeing with bexarotene, but we should see it at greater levels."

Scotland has one of the highest MS rates in the world, with around 15,000 people currently living with the disease.

Prevalence is highest in the north of the country and in Orkney, but it remains unclear exactly what causes the disease.

Prof Coles added that being able to combine existing MS drugs with a therapy capable of reversing damage at the point of diagnosis would have major implications for patients. 

He said: “In an ideal world, for someone newly diagnosed with MS, you’d get two types of treatment: you’d get the treatments available now which would stop any further damage by suppressing the immune system.

“There are 13 drugs that are now licensed in Scotland and England to do that.

“But what I also hope right from the outset is that they would get a drug, like metformin, that will repair damage that has already been done.

“The reason why that is really important early on is because the danger is that if you leave a nerve without myelin for too long, the nerve cell will degenerate.

“That’s what causes people with MS problems later on in life, when they get a progressive worsening of disability – it’s because nerve cells are dying off that years before were stripped of their myelin.

“So if we can give a re-myelinating therapy early on, maybe just for one or two years – that might be all that’s needed – and we can stop further damage being done, that really will be seriously good news for people with MS.”

Morna Simpkins, director of MS Society Scotland, said: "This new research is a major milestone in our plan to stop MS and we’re incredibly excited about the potential it’s shown for future studies.”