‘Major moment in MS research’ as new Octopus trial starts

By Caroline WyattBBC News

6 hours ago

Image credit: Ailsa Guidi

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Ailsa was diagnosed with multiple sclerosis when she was 22 years old

“I was playing a game of ultimate frisbee and had blurred vision in one eye – a bit like looking through a glass of steam.”

Ailsa Guidi was 22 at the time, studying at the University of Manchester.

“The doctor said it was optic neuritis, so I was treated with steroids and the blurriness went away. So I continued to be a student.”

Two years later, in 1999, her vision blurred again. This time, her GP was concerned it could indicate something more serious.

One Friday evening, Ailsa went alone for her first MRI brain scan with the neurologist who would give her a life-changing diagnosis.

“He said: ‘you have very mild multiple sclerosis’. At the time I knew several people who had MS and had to use a wheelchair. My eyes filled with tears and the neurologist asked me ‘why are you crying?’ I just told you that it is very soft”, recalls Ailsa.

“But I was 24, all my friends were getting together in the pub that night, and so for me, it was a really big thing to take on. Even if having milder MS was good, as he saw neurologist, for me diagnosed with MS was not.”

Ailsa started treatment and tried not to let the diagnosis change her life too much.

“At the time, I found it quite difficult to talk to friends about it because they were either so worried about me that I ended up telling them I was perfectly fine, or they just didn’t know much about MS,” recalls Ailsa. .

She saw the millennium in Barcelona with her boyfriend Robert, who studied at the same university. Later they got married and in 2005 their first child was born.

Image credit: Ailsa Guidi

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Ailsa went on to marry and have three children, and is now taking part in a trial of existing drugs to treat MS

MS is a neurodegenerative disease in which the immune system mistakenly attacks the fatty myelin sheath that protects nerves in a similar way to the insulation around electrical wires. As this protection is eroded, nerves can eventually stop being able to send signals that help us walk, talk, think clearly, or use our hands normally.

“A Milestone in MS Research”

Ailsa, now 47, is taking part in a ground-breaking new trial which is looking at whether existing drugs can be repurposed to help slow the progression of MS.

The way it is designed means that some drugs can be tried at the same time and others can be added or removed as the results come in.

The Octopus trial – so called because it is a multi-arm, multi-stage trial – is being led by Prof Jeremy Chataway, from the National Hospital for Neurology and Neurosurgery UCLH in London, with £13 million in funding from the UK MS Society. .

A similar trial model has been used to test drugs for prostate cancer and Covid.

Existing trial patients who prove to be on ineffective drugs can switch to a new arm and are allowed to continue any other MS disease-modifying drugs they may already be taking.

The first two drugs in the trial are high-dose metformin — a diabetes drug that can help regenerate myelin — and a high-dose version of alpha-lipoic acid, which is a dietary supplement that acts as an antioxidant. . It is already approved in Germany for the treatment of neuropathy – weakness, pain, numbness or tingling in damaged nerves.

The trial team spent several years narrowing down 100 potential drugs and will add more as other strong contenders emerge.

“We are at the start of a long journey,” says Prof Chataway. “There are now many treatments for relapsing MS, but far fewer available for progressive MS. This trial facility is like a drug testing machine for progressive MS. We hope to make it a lifelong machine – at least until we have what we want to control and ultimately reverse the progression of this difficult stage of MS.”

He thinks MS patients should eventually be able to take disease-modifying drugs to deal with the inflammatory component of MS and add any remyelinating drugs that prove to help repair or even stop nerve damage.

“This is a huge moment in MS research,” believes Prof Chataway. “Octopus has the potential to change the clinical trial landscape around the world, and we won’t stop until we have treatments that transform the lives of everyone with MS.”

The first 375 patients are already being recruited for the first phase of the trial, with the second phase bringing the total to around 1,000.

This month, Ailsa became one of the first people to be admitted to the trial, which aims to recruit to a further 30 centers across the UK as they are approved.

After a brain scan, blood tests and a full neurological examination, she has now received her first dose of trial medication.

Ailsa knows she may be in the placebo arm by not receiving any real treatment, but she hopes the Octapus trial will help doctors find ways to slow or stop the progression of MS and perhaps even repair some of the damage.

“I have trouble walking, but I can live with that. I just don’t want to get worse.”

‘The biggest impact is what MS takes away from you’

Ailsa took medical retirement at the age of 33 when it became clear that she could not manage her MS fatigue while working and caring for their three children while Robert worked full-time.

Robert, also 47, says MS has had a more visible impact on them as a family as the disease has progressed.

“In the beginning, things were quite normal. But now we have to plan a bit more and get the right equipment. It limits the scope of what you can do, so sports or dancing are no longer options. The biggest impact is the things MS takes away from you,” he says.

“Ailsa and I are a very close partnership and I think we’re both positive people. Everyone has their struggles in life so you just have to get on with it and enjoy life as much as you can.”

It has long been debated why the immune system goes rogue in this way for about three million people worldwide. A 2022 Harvard University study showed compelling evidence that the Epstein-Barr virus that causes glandular fever triggers the process. More research is underway in the hope that one day, MS can be prevented.

As Ailsa’s symptoms progressed, she went from using a cane or single crutch for balance, to a walker and now a wheelchair, trike or mobility scooter for longer distances, such as when walking the family Labrador with Rob or the kids.

“I think it’s important to be really open with kids so they understand MS and the impact in their own way,” she says.

“And obviously the impact changes. When the kids were young, they understood that it might mean you can’t get into the mom race at school, or you might have to do it in your own trike. And as the kids get older, they might have to help me push my wheelchair when I take them shopping.”

In February 2022, Ailsa was given the unwelcome news that she had switched from relapsing-remitting MS, in which symptoms often improve after a relapse, to having secondary progressive MS, where symptoms no longer go away after years cumulative nerve damage.

Around 130,000 people in the UK live with MS, and of those, tens of thousands – like Ailsa and me – live with a progressive form of the disease.

According to current guidelines from the National Institute for Health and Care Excellence, only two drugs – Siponimod and Extavia – are approved for secondary progressive MS, and not everyone will qualify for them.

Ailsa found out this spring that she doesn’t meet the criteria for Siponimod.

“That was a new thing to deal with, because dealing with progressive MS feels very different when you run out of disease-modifying drug options. It means your life has changed in pretty significant ways.”

‘The ability to revolutionize treatment’

Dr Emma Grey, assistant director of research at the MS Society, says the Octapod test should significantly speed up how quickly treatments can be tested.

“We wanted the trial to be as inclusive as we could, including people up to the age of 70 and those who can’t walk, because we often hear from people with more advanced MS that they can’t access studies of My hope is that with Octopus, we have created a world-first platform trial that has the ability to revolutionize the treatment of people with progressive forms of MS – and that this really changes the MS landscape for good.”

For people like Ailsa – and me – with more advanced MS, this test offers hope.

I am currently in the same hospital’s simvastatin MS-STAT2 trial, testing whether a high-dose statin can limit brain atrophy in MS. That trial is now drawing to a close.

If such repurposed drugs prove effective, it could help thousands of people with progressive MS who otherwise risk being told there is nothing more their doctor can do.