Clinical trials

A new hope for slowing disability in MS

ChariotMS will be the first multiple sclerosis clinical trial to include people who can’t walk. Natalie Healey talks to the MS Society about the trial and explores why new treatment options for patients with advanced stages of the illness are so desperately needed.

Jenny Ferguson, a 63-year-old former midwife from Norwich, has relied on a wheelchair for the last seven years. She was diagnosed with multiple sclerosis (MS) – a chronic condition of the brain and spinal cord – when she was 37. Today her only limb function is in her right arm and hand. She needs help with basic things like going to the bathroom, getting dressed and preparing food. 

As a keen painter, Ferguson’s right hand is her lifeline. “When MS meant I had to stop working, I started painting to save my sanity, and I’m grateful I can still enjoy that,” she says. “I think without painting there would be virtually no purpose to my day at all. Your life is only worth living if you’re happy with yourself - and being able to do things and have some independence is key to that.”

MS is a lifelong condition that sometimes causes serious disability. It leads to a variety of potential symptoms, such as problems with vision, movement and balance. More than a third of MS patients have significant difficulty walking. The condition can be divided into three main types: relapsing, primary progressive and secondary progressive. 

Around eight in ten people with the condition are initially diagnosed with relapsing MS. Patients will have episodes of new or worsening symptoms (relapses) that typically last for days to weeks to months, then slowly improve over a similar time period.

Many people with relapsing MS go on to develop secondary progressive MS, where they have a build-up of symptoms independent of relapses. While 10% to 15% of patients have primary progressive MS, which means the illness starts with a gradual worsening of symptoms, rather than appearing as sudden attacks. These problems accumulate over several years and there are no periods of remission.

Patients have been left behind 

For people with relapsing MS, there is some cause for optimism – there are more than a dozen licensed disease-modifying therapies for people with this type of the illness. But tens of thousands of patients with other forms of the disease in the UK do not have effective treatment. 

Patients like Ferguson who rely on wheelchairs have long been excluded from trials of new MS drugs as medicines have only been given the green light if they improve walking ability. As a result, there are currently no therapies licensed to preserve upper limb function in people with MS. 

“I have sometimes felt that people like me, with advanced MS, are not seen as important,” says Ferguson. “Being excluded from treatment and trials, and then being told there is nothing for you is very discouraging. If you can’t use your arms you are completely left behind, and we deserve to have the same hope as everyone else.”

Being excluded from treatment and trials, and then being told there is nothing for you is very discouraging.

However, hope could be on the horizon for people like Ferguson who have never before been eligible for a clinical trial. The first MS clinical study to focus on people who can’t walk will begin recruiting in early 2021.

The ChariotMS trial, led by Professor Klaus Schmierer at Queen Mary University of London & Barts NHS Health Trust, will investigate whether cladribine tablets (Merck’s Mavenclad) can slow the rate of upper limb disability progression in people with advanced MS. Cladribine is already licensed for relapsing MS. It works by preventing white blood cells from attacking the myelin covering around the nerves in the brain and spinal cord. 

“Traditionally, researchers thought this type of treatment wouldn’t work very well in more advanced MS because for these people, the damage is less likely to be caused by the immune attacks and more likely to be caused by progressive damage to the nerves,” says Dr Katie Howe, research communications manager at UK charity the MS Society. However, new evidence has emerged that suggests tackling the immune system in this way might still be effective for patients with advanced disease. 

The nine-hole test

MS clinical trials usually use walking ability as the key measurement for whether a treatment is effective, Howe explains – so people who use wheelchairs have been left out.

But the ChariotMS phase II trial will test whether cladribine can help people who can’t walk maintain the use of their arms, so will need a different test. Researchers will recruit 200 people who can’t walk further than 20 metres without crutches but still have some use of their arms and hands. 

Participants will be randomly assigned to take either cladribine or placebo over a two-year period. Throughout the trial, researchers will test the participants’ arm and hand function using an examination called the ‘nine-hole peg test’. Here, a patient sits at a table with a small, shallow container holding nine pegs and a block containing nine empty holes. 

Having a treatment that could preserve the use of my hand would make such a tremendous difference to my life.

When the researcher starts a stopwatch, the patient picks up the pegs one at a time as quickly as possible and puts them into the holes. Then, once all pegs are in the holes, the patient removes them again as quickly as possible and puts them back in the container. Researchers record the total time it takes to complete the task. And they will also look at MRI scans of the participants to work out whether cladribine has an effect on lesions in the brain. 

Howe says ChariotMS is “an incredibly exciting development” and points out it has only been made possible thanks to close collaboration between government, charity and commercial funders.

If cladribine is shown to slow the worsening of disability for people with advanced MS, a larger phase III will then be needed to confirm the findings. But if this is successful, it could mean patients with advanced MS get access to a disease-modifying treatment that will help them continue the activities that make their life fulfilling.

“Having a treatment that could preserve the use of my hand would make such a tremendous difference to my life,” says Ferguson. “It would be huge.”