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Three new MS subtypes identified

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Three new subtypes of multiple sclerosis (MS) have been identified by using artificial intelligence (AI). 

The new MS subtypes were defined as ‘cortex-led’, ‘normal-appearing white matter-led’, and ‘lesion-led.’

The study, by scientists at UCL, has been hailed as potentially being key in identifying those people more likely to have disease progression and help target treatments more effectively. 

“Currently MS is classified broadly into progressive and relapsing groups, which are based on patient symptoms; it does not directly rely on the underlying biology of the disease, and therefore cannot assist doctors in choosing the right treatment for the right patients,” says Dr Arman Eshaghi, from UCL Queen Square Institute of Neurology. 

“Here, we used artificial intelligence and asked the question: can AI find MS subtypes that follow a certain pattern on brain images? 

“Our AI has uncovered three data-driven MS subtypes that are defined by pathological abnormalities seen on brain images.”

MS affects over 2.8 million people globally and 130,000 in the UK, and is classified into four ‘courses’, which are defined as either relapsing or progressive. 

Patients are categorised by a mixture of clinical observations, assisted by MRI brain images, and patients’ symptoms. These observations guide the timing and choice of treatment.

For this study, researchers wanted to find out if there were any—as yet unidentified—patterns in brain images, which would better guide treatment choice and identify patients who would best respond to a particular therapy.

They used the UCL-developed AI tool, SuStaIn (Subtype and Stage Inference), to the MRI brain scans of 6,322 MS patients. The unsupervised SuStaIn trained itself and identified three previously unknown patterns.

Once SuStaIn had completed its analysis on the training MRI dataset, it was then used to identify the three subtypes in a separate independent cohort of 3,068 patients, validating its ability to detect the new MS subtypes.

“We did a further retrospective analysis of patient records to see how people with the newly identified MS subtypes responded to various treatments,” adds Dr Eshaghi.

“While further clinical studies are needed, there was a clear difference, by subtype, in patients’ response to different treatments and in accumulation of disability over time. This is an important step towards predicting individual responses to therapies.”

NIHR Research Professor Olga Ciccarelli, of UCL Queen Square Institute of Neurology, and the senior author of the study, adds: “The method used to classify MS is currently focused on imaging changes only; we are extending the approach to including other clinical information.

“This exciting field of research will lead to an individual definition of MS course and individual prediction of treatment response in MS using AI, which will be used to select the right treatment for the right patient at the right time.”

Researchers say the findings suggest that MRI-based subtypes predict MS disability progression and response to treatment and can now be used to define groups of patients in interventional trials. Prospective research with clinical trials is required as the next step to confirm these findings.

MS

World-first MS trial to test existing drugs

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A world-first trial is being launched in the UK into whether drugs already on the market can prevent multiple sclerosis (MS) from worsening and even reverse the disabilities it causes.

The Octopus trial will investigate the potential benefits of using a number of different medications at once, in the hope of finding effective new treatments up to three times faster than if the medicines were trialled separately.

Octopus – named because of its many arms – marks the culmination of years of planning for the ‘mega trial’ for progressive MS. 

University College London has been announced as delivering the trial, with the MS Society confirming contracts have been signed, with Professors Jeremy Chataway and Max Parmar leading the research.  

The initial drugs to be tested will be announced later in the year, with hundreds of patients being sought to participate. The trial will be randomly assigned to have either standard care for progressive MS or standard care plus one of three drugs that doctors hope will at least protect their neurons from the disease if not repair the damage done.

“In conventional trials, one group of people take the potential treatment. Another ‘control’ group take either an inactive placebo or a treatment already available for MS,” explains Dr Emma Gray, assistant director of research at MS Society. 

“And each treatment goes through several ‘phases’. You start with a small group of people. If the treatment looks promising, you set up more trials with increasingly larger groups. 

“Although this approach works, it takes a really long time. Octopus will speed things up by merging lots of these trials into one.” 

About 130,000 people in the UK live with MS. The condition arises when the immune system mistakenly attacks the fatty myelin sheaths that wrap around nerves in the brain and spinal cord. Without the lipid-rich coating, electrical signals travel more slowly along nerves, are disrupted or fail to get through at all. 

Through this multi-arm, multi stage (MAMS) design trial, Octopus will test multiple drugs at once, comparing them with a single control group, and are able to eliminate drugs from the trial at an early stage. More can then be added in, in a means of effectively merging two trials.  

“Merging separate trials may sound obvious,” says Dr Gray. 

“But launching a MAMS trial for MS needs so many things to line up perfectly, from hospitals around the country equipped to be trial sites, to the incredibly complicated statistics that underpin the design.”

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MS

MS medication approved for use in Scotland

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A final decision on rolling out the medication to the rest of UK is expected in the coming months

Approval has been given for use of a multiple sclerosis (MS) medication in Scotland, with a final decision on its introduction in England and Wales expected later this year.

The medication ozanimod, or Zeposia, has been given approval by the Scottish Medicines Consortium (SMC) for people with active relapsing remitting MS.

Ozanimod is a disease modifying therapy which is taken as a tablet and traps immune T-cells in the body’s lymph nodes.

In a two year clinical trial, it was shown to reduce relapses in those with active relapsing remitting MS by around 38 per cent, compared to beta interferon, an existing MS treatment.

Scotland is the first nation in the UK to approve ozanimod and its approval means there are now 15 disease modifying therapies available on the NHS in the country.

In January, the National Institute for Health and Care Excellence (NICE) provisionally decided not to recommend the drug for use in England and Wales, although a final decision is expected in the coming months.

In NICE’s preliminary decision, it cited the uncertainty around how effective ozanimod is compared to other treatments, and cost-effectiveness estimates are uncertain because of limitations in clinical evidence.

MS charities have welcomed the decision to introduce ozanimod in Scotland, with its use in tablet form providing an option for people who find injectable therapies difficult to administer and widening existing options.

“It’s very welcome that ozanimod has been approved for use on the NHS in Scotland. MS is relentless, painful, and disabling, and this treatment increases the options for people to manage their condition and help prevent symptoms,” says Morna Simpkins, director of the MS Society in Scotland.

“Our community’s experiences tell us just how big a difference having different treatments available can make.

“We hope that appraisal bodies in other parts of the UK follow suit as soon as possible, so everyone with MS can access ozanimod if it’s the right option for them.

“We have never been closer to stopping MS, and this is just the latest in a number of new treatments which have been made available in the past few years for the 15,000 people living with MS in Scotland.”

David Martin, chief executive of the MS Trust, hailed its introduction in Scotland as “excellent news”.

“The approval of Zeposia in Scotland increases the choices for people with relapsing MS, particularly those who prefer taking a tablet,” he says.

“An expanding range of drugs that work in different ways and have different benefits and risks means more people can find the treatment that is best for them.”

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MS

MS research reveals sight breakthrough

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The findings come from a recent study held by UC Riverside School of Medicine

Vision in patients with multiple sclerosis (MS) could be improved through the use of medication, a new study has found.

A mice study investigated the effect of indazole chloride (IndCl) on the pathology and function of the afferent visual pathway for the first time, which includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

“IndCl has been previously shown in mice to reduce motor disability, increase myelination, and neuroprotection in the spinal cord and corpus callosum,” says Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study’s lead author.

“Its effects in the visual system, however, were not evaluated until now.

“Our study shows the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, are able to restore some function with IndCl treatment with successful attenuation in inflammation and an increase in remyelination.”

In MS, damage can often be caused to the optic nerve and other parts of the visual system, which results in around 50 per cent of patients with MS experiences optic neuritis – inflammatory demyelination of the optic nerve – prior to showing initial symptoms.

Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.

The researchers used IndCl to assess the impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.

The visual pathway in mice is similar to that in humans, say researchers. In the lab, Professor Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days, and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice.

At the end of the experiment, they performed functional assay to measure the visual electrical signal, and immunohistochemistry to examine the visual pathway.

The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.

“Measuring visual function and recovery in the presence of novel therapies can be used to screen more effective therapies that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage,” says Professor Tiwari-Woodruff.

Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.

“We treated the MS mice with IndCl at peak disease,” Professor Tiwari-Woodruff says.

“If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There’s a point of no return.

“Our paper stresses that to acquire vision improvement, treatment must start early. Early treatment can recover 75%-80% of the original function.”

Tiwari-Woodruff stresses that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.

“There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS,” Professor Tiwari-Woodruff adds.

“Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good oestrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment.”

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