In the News

All the latest must-read MS research and stories

High-dose vitamin D does not reduce MS disease activity

High-dose vitamin D does not lessen the risk of disease activity for people with multiple sclerosis (MS), data from a new clinical trial indicates.

Patients aged 18 to 50 with relapsing remitting MS were enrolled at US neurology clinics between 2012 and 2019. They had to have an Expanded Disability Status Scale of less than four and have had no more than 1,000 IU of supplemental vitamin D on average daily for the previous 90 days. All were being treated with glatiramer acetate (Copaxone).

They also had to have blood levels of vitamin D of 15 ng/ mL or more, because it is unethical to enrol people who have a deficiency in a clinical trial in which they may be given a low dose.

Patients were randomly assigned low (600 IU) or high (5,000 IU) doses a day for approximately two years.

Researchers said the low dose was effectively a

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placebo as they didn’t expect to see any kind of change in MS activity with this amount.

In the patients receiving the high dose, average blood vitamin D levels rose substantially, and in the lowdose group, levels were generally stable.

Researchers made comparisons between the rates of radiologically-measured change in MS, such as active inflammatory lesions, new and emerging lesions, and rates of brain shrinkage.

There were no statistically to [glatiramer acetate] therapy, does not reduce imaging measures of disease activity in established RRMS.”

Although this trial tested vitamin D alongside glatiramer acetate specifically, the researchers said they’d expect the results to be similar with any disease-modifying therapy.

Researchers compared rates of active inflammatory lesions, new and emerging lesions and brain shrinkage

significant differences in any of these measures between the two groups, leading the researchers to conclude that “high dose vitamin D3 supplementation, as add-on

The results were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, Feb. 23-25 in San Diego.

Baclofen is one of the drugs licenced to treat spasticity in people with MS, but a new Swedish population-based study showed half of patients discontinued it in the first month, and 90 per cent stopped within two years.

When accounting for people with incident MS and prevalent MS, 65 per cent stopped baclofen within a year.

Patients who were more disabled, scoring higher on the expanded disability status scale (EDSS), kept on the treatment longer.

Two other treatments commonly used to treat spasticity, diazepam and gabapentin, also showed high discontinuation rates among MS patients – with those in the study almost all discontinuing after six months and 75 per cent stopping gabapentin after a year.

The researchers said that the results highlighted “the importance of informed treatment options and better understanding of spasticity in general among patients with MS.”

Smokers with MS now have another reason kick the habit

Smoking is linked to higher prevalence of anxiety and depression in people MS, a new systematic review has found.

Across all of the studies analysed, smoking was associated with a 1.3-2.3 times higher depression prevalence, and around a 1.2 times higher rate of anxiety.

The results indicated that stopping smoking seemed to help anxiety levels, but not depression.

Researchers said more studies were needed to investigate the links because of the different ways the studies in the review were reported made interpreting the results challenging.

It’s well established that smoking is linked with MS development, plus worse disability progression and higher risk of relapsing remitting MS converting to secondary progressive.

Overall, smoking was linked with a 20 per cent increase in risk of anxiety. One study found depression in current smokers was found to be 2.3 times higher than in non-smokers, and another found depression increased at a faster rate in current smokers than in those who had never smoked.

The researchers suggested the link could be due to tobacco’s inflammatory and immunomodulatory effects and noted this might negate the immune-modulating effects of disease-modifying therapies.

If you want to quit smoking, call MS-UK’s Helpline on 0800 783 0518 and download our MS and Smoking Choices booklet at ms-uk.org/choices-smokingand-ms-content/

SPMS gut bacteria clue

Scientists have identified a certain species of bacteria which may drive disability progression in people with secondary progressive multiple sclerosis (SPMS) they announced in a recent presentation at the Americas Committee for Treatment and Research in Multiple

Sclerosis (ACTRIMS) Forum 2023, held Feb. 23-25 in San Diego.

Due to patient protection, the team couldn’t release the name of the bacteria, instead naming it ‘bacteria X’. But when taken from SPMS patients and given to mice with MS, the rodents developed more neurological disability and more immune cells that are implicated in the inflammation behind MS.

Scientists think this species of bacteria’s flagella, which are hair-like parts it uses to move around and invade cells, are what promote the inflammation.

The research team had analysed stool samples

Blood marker can identify risk of silent disability progression

The levels of a protein called glial fibrillary acidic protein (GFAP) in the blood of people with MS can help to predict disability that happens in the absence of relapses – often called silent progression, according to a new study.

Relapses are often the main driver of MS disability, but for those who experience worsening disability without them, there are no clinical biomarkers that can predict it.

Researchers found that levels of neurofilament light chain protein (NfL), a protein from nerve cells that’s a well-established marker of a relapse, went up by 53.2 per cent during relapses, but GFAP levels changed less than 5 per cent. But in those with silent progression, GFAP were 57.5 per cent higher and NfL only 28 per cent higher.

NfL levels also were significantly associated with silent progression in people who were being treated with Ocrevus.

The researchers said the results previously from people with both relapsing remitting MS and SPMS and had found a distinct gut bacteria profile that was associated with each type. support GFAP being a useful biomarker for predicting progression independent of relapse activity risk, and back up previous research identifying NfL as a marker of relapse activity.

Two different subtypes were identi ied within bacteria X, with one signiicantly more abundant in SPMS patients compared with RRMS patients and healthy people.

Whether there is a “causal relationship between gut dysbiosis and MS progression remains elusive,” said the researchers, adding that if a relationship should be confirmed, the specific “diseaseenhancing causative bacteria” remain to be identified.

They said more research is needed, in particular a need to assess whether GFAP can predict PIRA in MS patients on other therapies.

Teenagers who sleep poorly – less than seven hours a night – are between 40 and 50 per cent more likely to go on to develop MS later on than those who have good sleep, a recent populationbased study from Sweden has found.

Research has investigated the affect of shift work, and particularly at a young age, and found it raises the risk of MS. It’s also known that poor sleep quality stimulates proinflammatory pathways and it’s thought this can increase the risk of inflammatory diseases.

Poor sleep quality and duration had, however, not been thoroughly examined.

To investigate, Swedish researchers used data from the Epidemiological Investigation of

Multiple Sclerosis which was launched in 2004 and features people aged 16-70 from the general population of Sweden. Overall the results showed that people who slept less than seven hours a night in adolescence were 40 per cent more likely to get MS in later life, compared to people who slept for seven to nine hours. Those who slept longer at weekends but still less than seven on a weekday (or work day) still had a 30 per cent increased likelihood. The association remained after researchers adjusted for other risk factors like smoking, body fat and Epstein-Barr virus infection. Other conditions at the age of 20 and at the onset of MS did not affect the findings, neither did the mean weekly sleep duration.

The study then looked at sleep quality. Those with low quality in adolescence were 50 per cent more likely to develop MS than people who reported good to very good sleep. This association was still significant whether people slept for more or less than seven hours.

The researchers said that the findings should be interpreted with cautious because it’s not known if reverse causation was at play.

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Molecule triggers remyelination in MS in new study

A signalling protein called fractalkine promoted myelin repair in a new study in a mouse model of MS.

Fractalkine triggered new growth of myelin-producing cells, oligodendrocytes, and also reduced pro-inflammatory immune cells in the brain.

The protein has been shown in previous studies to help stimulate oligodendrocyte precursor cells to turn into mature oligodendrocytes more quickly.

For the study, mice were fed cuprizone for six weeks, which causes loss of myelin. Fractalkine was then infused directly into their brains for three

Promote Remyelination

In a mouse model of MS, combining Mayzent (Siponimod) and vitamin D was found to improve motor function and help restore damaged myelin sheath.

Researchers in Saudi Arabia divided mice with MS into four groups. Untreated control, oral vitamin D3 treatment, Mayzent, and a combination of vitamin D3 and Mayzent. Each group was then examined during the early remyelination phase (week 5 to week 7.5), and late remyelination phase (week 7.5 to week 9).

The mice who were treated with the combination, or just vitamin D alone, performed better on speed tests, in the earlier phase but not in the later one. Mayzent on its own didn’t seem to affect their walking speed. The mice given the D3/ Mayzent showed an increase in the distance they could travel, but the other groups didn’t.

Myelin basic protein, which experts believe plays a big role in remyelination, was significantly increased in the mice given the vitamin D/Mayzent combination days. The mice were then given a normal diet to allow myelin formation to begin. compared with untreated mice, but not in the mice given either the single vitamin D or Mayzent.

Oligodendrocyte precursor cells and mature oligodendrocytes increased up to double the amount in the treated mice. The molecule also reduced the number of immune cells that travel round the brain and spinal cord and are thought to contribute to MS – proinflammatory microglia. Fractalkine also increased myelin density.

Testing found that fractalkine acts on the microglia and the oligodendrocyte precursor cells to increase oligodendrocyte formation. The study’s authors said fractalkine ‘represents a novel candidate for remyelination strategies.’ It will be tested in other disease mouse models.

The research team said that the vitamin D3 plus Mayzent combination shows promise as a future treatment for human patients.

Possible new biomarker for MS diagnosis discovered

Researchers have discovered a new possible biomarker for the diagnosis and prognosis of MS.

Myelin basic protein, a key myelin protein in the sacs of cellular content that are released by oligodendrocytes – which are the myelin-producing cells of the brain and spinal cord – was found at significantly higher levels in people with MS than in healthy people. Additionally, primary progressive patients had higher levels than those with relapsing remitting MS.

A diagnosis is currently made based on imaging, clinical and laboratory information, but a non-invasive, quick and easy test for biomarkers isn’t available. Oligodendrocytes release tiny membrane-coated sacs called extracellular vesicles. These contain proteins, fats and material from the original cell. Researchers examined whether the amount of myelin proteins in them could help diagnose MS and help with prognosis.

The results showed that myelin basic protein levels in the extracellular vesicles from the healthy control group in the study were significantly lower than in people with MS, and the concentration found allowed the researchers to discriminate between people with MS and healthy people with a 96.3 per cent accuracy. people with MS who did intermittent fasting for eight weeks had cognition and manual dexterity improvements, and also had less fatigue and pain scores. The criteria of the fasting programme was that participants had to eat their meals within an eight-hour window only, with the other 16 hours of the day spent fasting.

The results indicate that ‘a minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis,’ the researchers said.

The participants had a mean age of 46 and 83 per cent were women. One person dropped out of the trial.

Positive reports included two people noticing they slept better, and others said they lost weight, had more energy, less acid reflux and feeling better overall. Negative reports included headaches, constipation and having to schedule their social lives around the eating times. After eight weeks, clinical outcomes were assessed. Fasting was found to have improved hand and finger dexterity and cognition. Pain and fatigue scores had lowered, although they were not deemed to be statistically significant, the researchers called them ‘clinically significant’.

The study’s authors said this study only focused on timings of food rather than food type.

Anxiety, depression and MS

The rate of psychiatric symptoms such as anxiety and depression is higher in people during the five-year lead up to diagnosis with MS than it is in healthy people, a new analysis has found.

Mental health problems are common among the MS population. But before diagnosis many patients notice health changes which aren’t suggestive of MS, including sleep disorders. This study set out to see if psychiatric symptoms were implicated.

Researchers analysed the data from 6,863 Patients with MS, matched for sex, age and location with up to five healthy people from the general population who were the control group.

They found depression, bipolar disorder, anxiety, and

New study on omega 3 and MS

A new study has shown that consuming omega 3 fatty acid may be beneficial to people with MS after it reduced inflammation and disease severity in a mouse model. Researchers investigated the effects of DHEA, a molecule in omega 3 fatty acid. Mice with experimental autoimmune encephalitis, a mouse model of MS, had DHEA injected into their abdomens.

schizophrenia had a significantly higher prevalence in the MS group than the control for the five years before disease onset. The prevalence seemed to get higher as the onset date approached.

A total of 28 per cent of the MS participants and 15 per cent of the control group had psychiatric issues during the five-year period. This is an 88 per cent greater risk for the MS group.

Depression was the most common symptom, anxiety was the second.

The team also noted mental health-related doctor visits were 125 per cent more frequent in MS patients than the controls and visits to psychiatrists were 150 per cent more common in the year before diagnosis. Hospital admissions were also up for MS patients by 130 per cent five years prior to onset, rising to almost 200 per cent by one year to onset. Psychiatric medication prescriptions were up by 75 per cent five years prior and 100 per cent at one year to onset.

The rodents treated with DHEA developed MS symptoms more slowly than mice given an inactive solution.

The study found that some mice didn’t respond to the DHEA treatment. In some of the DHEA-treated mice, there were longer remission periods between the beginning of their disease and another relapse, while some developed MS at the same time as the mice who weren’t treated.

When analysed, tissue from the nervous system of the mice had a reduced number of inflammatory T-cells – something the researchers had shown DHEA to be capable of doing with cells in dishes in the lab.

They concluded that DHEA can affect T-cell polarisation and affect T-cell effector function, which gives a positive outcome in MS and autoimmune disease.

Salt implicated in MS development in study

Salt disrupts the ability of certain cells whose job it is to control inflammation and combat autoimmunity, a new study has found.

Salt rendered regulatory T-cells (Tregs) less effective at controlling a mouse model disease of MS. Tregs dampen parts of the immune system and help control activity that could damage the body’s tissue. Scientists think when Tregs are unable to suppress other immune activity this might contribute to autoimmune conditions such as MS.

Plant compound decreased MS severity

Mice treated with a plant compound called berberine had decreased disease severity in a mouse-model of MS, a new study has found. Berberine is a compound found in plants such as tree turmeric, European barberry and goldenseal. Previous research has found berberine to have

A high-salt diet, which is common in the Western world, has been shown to make Tregs more pro-inflammatory. Tregs exposed to salt look similar to autoimmune Tregs found in conditions such as MS.

In cell cultures, the gene activity of cells exposed to salt was also changed. Similarly altered genes were observed in MS patients.

Researchers then injected Tregs from healthy mice, which were then cultured in salt, into anti-inflammatory and neuroprotective properties. In this study, Iranian scientists treated mice with experimental autoimmune encephalomyelitis, a mouse model of MS, with either berberine or a salt water inactive treatment. a mouse model of MS. Normal Tregs could stop MS developing in the mice, but the ones exposed to salt could not.

Mice treated with the plant compound retained greater body weight, which is generally an indicator of better health.

Disease severity measures were also significantly lower in the group given berberine, and a greater effect was seen with higher doses, with disability and paralysis severity decreased.

Analysis of tissues showed the brains of the mice who received berberine had fewer inflammatory cells and there was less evidence of demyelination.

Inhibiting a molecule called NCLX, which allowed the Tregs’ mitochondria to take up salt, restored the ability of the Tregs to control disease again. Researchers said this could show promise for the treatment of salt-sensitive diseases, more work is required to properly understand the molecular mechanisms.

There were also less proinflammatory signalling molecules, and a higher level of anti-inflammatory molecules.

“These results confirmed that treatment with berberine improved the disease in the animal model of MS,” said the researchers, noting the study’s results suggest the compound may be a promising therapeutic approach for people with MS.

Please note this study was done on mice and not humans with MS. Always speak with your doctor before taking a supplement. Although berberine is available to buy as an overthe-counter supplement it is likely unsafe for some people to take and more research is needed to establish exactly for whom it is safe.