What’s New in MS Research – September 2025

Are telltale signs of MS present more than 10 years before diagnosis?

People with MS make increased use of healthcare services up to 15 years before recognized onset of the neurological disease, a team of Canadian researchers report. This suggests that the condition may often be present long before it is identified.¹

The investigators reached that conclusion after examining more than 25 years’ worth of records for 12,200 people who received care in the Canadian province of British Columbia. Slightly more than 2,000 of the study subjects had been diagnosed with multiple sclerosis. Seventy-four percent of people in the MS group were women, and group members’ average age at symptom onset was 37.9 years. The other 10,082 people in the study served as a matching cohort for purposes of comparison, with each person with MS matched with up to five individuals based on sex, birth year, socioeconomic status, and residential postal code.

In the 14 years before recognized MS onset, the people with multiple sclerosis had 19% more physician visits – on average, and for any reason – than their counterparts. In the year before onset, they had 28% more visits.

When looking at specific reasons for a person seeing the doctor, researchers found that visits for signs and symptoms without a clear cause were consistently elevated 15 years before recognized MS onset, with the rate of visits being almost 1.5 times higher among people with MS than their matched controls in the year prior to onset. Visits related to mental health were higher in all but three of the 14 years before MS onset.

Not surprisingly given the nature of MS, visits for sensory issues were elevated in the eight years before onset, while visits for musculoskeletal and nervous system complaints were increased relative to the matched cohort five and four years, respectively, before MS onset. In the year prior to onset, visits for neurological issues were 2.4 times higher in the MS group than in the comparison group.

Looking at the data in terms of type of physician seen, people with MS started having a relatively greater rate of visits to psychiatrists 12 years before recognized onset and neurologists and ophthalmologists eight to nine years before MS onset. The study’s authors concluded, “Mental health and psychiatric issues along with ill-defined signs and symptoms might be among the earliest features of the prodromal period [a “prodromal period” is a prelude to the emergence of a condition marked by potentially telltale signs], preceding nervous system–related and neurologic visits” by many years.

People with MS often report feeling that “something just wasn’t right” years before their diagnosis. While many of the symptoms those people experienced aren’t specific to MS and could be caused by any number of conditions, this study suggests that a “prodromal period” may, indeed, precede the clear onset of MS. If so, further research may be directed toward identifying a set of symptoms or clinical findings that indicate an elevated risk for MS and that warrant periodically monitoring at-risk individuals via magnetic resonance imaging (MRI) and other means.

 

– Back to index –

 

Encouraging findings on impact of DMTs in late-onset MS

Starting a disease-modifying therapy (DMT) within three months of being diagnosed with relapsing-remitting MS can be beneficial to adults regardless of whether they are older or younger than age 45, according to a recent study.²

Because the favorable impact of DMTs is believed to decrease with age, neurologists have long pondered whether the risks of initiating therapy in people with late-onset MS – generally defined as symptom onset after age 45 – outweigh the benefits those medications offer. To explore this question, researchers affiliated with an MS center in London conducted a prospective study in which they followed 1,644 people with relapsing forms of MS over two years. Of that total, 1,494 people were diagnosed between ages 18 and 45 years, with 29.6 being the average age of disease onset. They compared that group’s outcomes with those of 150 people diagnosed at age 46 or later. The average age at disease onset in this group was 50.6 years. More than 70% of people in both groups were female.

At the start of treatment, the people in the older group had a higher average Expanded Disability Status Scale (EDSS) score than their younger counterparts, indicating a greater degree of disability, and more non-MS health conditions, which medical professionals call comorbidities. After adjusting for potentially confounding factors (these are variables that are not the main focus of a study, but can confuse or mislead the findings), the researchers found no difference between the groups at Year 1 in terms of probability of relapses, worsening EDSS score, or developing evidence of disease activity after not having had such evidence. At Year 2, similar results were observed in terms of those measures and with MRI activity.

A second analysis that focused on people who were diagnosed and started a DMT at age 50 or older yielded comparable findings. Further, the rate of stopping medication due to side effects was similar between the two groups. In treating MS, neurologists work very hard to maximize the benefits of a medication while minimizing the potential for side effects. As people age, it is common for them to develop additional health conditions, such as diabetes and high blood pressure. Many of those conditions, as well as the normal aging process, can affect how the body metabolizes MS therapies.

Further, the medications that people take for their other conditions may interact with MS treatments in adverse ways. Combine those factors with the observation that the inflammatory component of MS tends to decrease with age and it is easy to understand how challenging it can be for clinicians to assess the risk:benefit ratio for patients diagnosed in their late 40’s or beyond. This study, while conducted at a single center and involving a relatively small number of people with late-onset MS, contributes important – and reassuring – evidence about the value that DMTs can provide regardless of age at diagnosis.

 

– Back to index –

 

Can a diabetes medication promote remyelination in MS?

Laboratory research suggests that metformin, an oral medication long used to treat diabetes, may facilitate the development of human oligodendrocytes, the cells that produce the myelin sheath that insulates the ends of neurons, enabling efficient transmission of electrical impulses.³ In MS, damaged – or sclerosed – areas of myelin sheath slow or disrupt the transmission of those impulses, interfering with the brain’s ability to send signals to other parts of the body.

Earlier research showed that metformin rejuvenates oligodendrocyte progenitor cells (OPCs) in adult rats. A progenitor cell is a descendant of a stem cell. It has the ability to develop and differentiate into one or more specific cell types in a particular tissue or organ, such as oligodendrocytes in the central nervous system.

Based on those animal-model studies and other research, a number of clinical trials are being conducted to assess the impact of metformin on people with MS. While investigators await the results of those trials, an international team of scientists examined how metformin affects OPCs derived from human stem cells. After conducting tests using three different types of tissue samples, they found that metformin increased myelin proteins and/or sheaths in all three.

These findings are exciting, but it is important to emphasize that this research was conducted in tissue samples, or cultures, not in people. The ongoing clinical trials assessing the efficacy and safety of metformin in people with MS will yield the results that matter the most. While we await the outcome of those trials, however, it is encouraging to know that researchers continue to move forward in their search for medications that can repair damaged neurons and, hopefully, restore function as a result.

 

– Back to index –

 

Walking in place can take you far – and in just six weeks

Living with MS sometimes can feel like walking on a treadmill: You keep taking steps but they may not seem to get you as far as you would like to go. If you’ve ever had that sense, here’s some good news: Actually walking on a treadmill can increase walking distance while easing the perceived difficulty involved.

Those findings come from a French study involving 46 people with MS who had a moderate degree of disability.⁴ Researchers assigned study participants at random to a treatment group that had 18 treadmill training sessions over six weeks or to a control group.

At the end of the six weeks, the people in the treatment group had a statistically significant improvement from baseline in a six-minute walk distance and reduction in their sense of walking difficulty.

 

– Back to index –

 

Study suggests that Vitamin D may reduce disease activity in participants with MS precursor

People who took Vitamin D supplements after experiencing a first demyelinating event had significantly less MS-related disease activity over the following 24 months than other people who had a demyelinating event but did not take Vitamin D.⁵

French researchers reported that finding after studying more than 300 people over the course of 10 years. The study subjects all had clinically isolated syndrome (CIS), the term physicians use to describe a single event, such as numbness or weakness in a limb, the visual disturbances of optic neuritis, or other neurologic event indicating that the myelin sheath coating a nerve has been damaged. People with CIS are at high risk for later being diagnosed with MS.

Because Vitamin D deficiency is known to be a risk factor for MS, the researchers wanted to see how giving people with CIS a regular Vitamin D supplement would affect their subsequent course.

The people studied were between 18 and 55 years of age, had CIS for less than 90 days, and had serum Vitamin D concentrations less than 100 nmol/L. None had received medications for their demyelinating event and all had imaging or fluid-based biomarker results consistent with a demyelinating event. The trial, which was conducted at 36 MS centers in France, assigned people at random to receive either 10,000 units of cholecalciferol (a form of Vitamin D) or placebo by mouth every two weeks for 24 months. The participants’ median age was 34 years and 70% of study participants were women. The study’s primary endpoint was disease activity, defined as occurrence of a relapse and/or MRI activity, such as new or contrast-enhancing lesions seen on imaging.

Among the people who completed the 24-month trial:

• Disease activity was observed in 60.3% in the Vitamin D group and in 74% in the placebo group.
• Median time to disease activity was 432 days in the Vitamin D group versus 224 days in the placebo group.
• New lesions were seen on MRI in 46.2% of patients in the Vitamin D group as compared to 59.2% of people in the placebo group.
• Contrast-enhancing lesions were found on MRI in 18.6% of the Vitamin D group members and in 34.0% of those receiving placebo.

All four of the differences between groups cited above were statistically significant, meaning that they were unlikely to be due to chance. Several other outcome measures showed a trend favoring Vitamin D supplementation but were not statistically significant. These included relapses when examined alone rather than along with MRI activity, as it was in the primary outcome measure. The incidence of a relapse was 17.9% in the Vitamin D group versus 21.8% in the placebo group.

Seventeen people in the Vitamin D group and 13 in the placebo group had severe adverse events during the study, but researchers investigating those events determined that none were related to cholecalciferol. Those researchers concluded, “These results warrant further investigation, including the potential role of pulse high-dose Vitamin D as add-on therapy.”

Because low levels of Vitamin D have long been known to increase risk for MS, numerous studies have explored whether giving people supplements of this vitamin can reduce that risk or improve outcomes in those already diagnosed with the condition. The results of those studies have been mixed. Further, because the studies sought answers to different questions, employed different designs, and focused on different patient populations, it has been difficult for clinicians to derive definitive guidance from them. With this French trial showing positive results, it seems clear that the role of Vitamin D will continue to be explored.

Meanwhile, people interested in exploring whether they might benefit from Vitamin D should discuss the option with their MS provider rather than starting an over-the-counter supplement or any other medication on their own.

 

– Back to index –

 

French study finds that compared to men, a lower proportion of women receive DMTs, although family planning is a big factor

While women are more likely than men to develop MS, one study found that they are less likely than men to receive disease-modifying therapies (DMTs) to treat the condition. That finding emerged from a study in which researchers drew on a French database to analyze information on 22,657 people with multiple sclerosis.⁶ Study participants all experienced onset of relapsing-remitting MS between ages 18 and 40 years. Seventy-four percent of the people studied were female. Study participants’ average age at MS onset was 29 years, and participants were followed for a median of 11.6 years.

The study’s female participants were 8% less likely than men to receive any DMT and 20% less likely to receive a high-efficacy DMT. Gender-based differences in treatment patterns appeared one year after MS onset for the high-efficacy medications and two years after disease onset for DMTs overall.

In exploring possible reasons for these differences, researchers analyzed data on 5,268 women who gave birth to their first child during the study period. They found that the proportion of those women who were receiving a DMT declined from 42.6% at 18 months before childbirth to 27.9% at the estimated time of conception.

Based on this finding, the investigators concluded, “Anticipation of pregnancy was probably an important factor underlying this difference, but also sex-specific therapeutic inertia” may be a factor. They added, “Neurologists and patients should be educated on the most recent recommendations on the use of DMTs in the context of pregnancy to avoid deleterious therapeutic inertia.” (Deleterious therapeutic inertia refers to a patient failing to begin or increase treatment when recommended, and this delay in treatment has led to a missed opportunity for early intervention to slow the disease process and/or to reduce the chances of long-term health complications.)

The study authors’ conclusion underscores the importance of women talking with their MS providers well before pursuing pregnancy in order to fully understand and weigh the benefits and risks of any decision about continuing or stopping DMT use.

Two caveats also warrant mention. First, while the biology of MS doesn’t vary based on where a person lives, the psychology of treating the disease may. People with MS and clinicians in France may – on the whole, allowing for individual variation – be more or less risk averse, i.e., less willing to take a risk, than patients and providers in the United States. Second, the study focused on people in the prime of their childbearing years. Hopefully, any gender-based differences in DMT treatment end once pregnancy is no longer a consideration, but other studies are needed to explore that issue.

 

– Back to index –

 

How looking people in the eye may reveal a lot about their MS

Optical coherence tomography, or OCT, is a painless, non-invasive, office-based test that uses light waves to create high-resolution images of a person’s retina. Software programs analyze those images to measure the thickness of different retinal layers and the optic nerve, allowing identification of the nerve inflammation and swelling that occur when a person with MS has optic neuritis.

Now, however, research suggests that this sophisticated means of “looking a person in the eye” may provide physicians with even greater insights into the nature of a patient’s secondary-progressive multiple sclerosis (SPMS).

Researchers participating in a substudy of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) analyzed clinical findings, brain magnetic resonance imaging (MRI) scans, and OCT results for 192 people with SPMS, looking at differences from baseline to Week 96 of the trial.⁷

The investigators found that baseline OTC measurements indicating the thicknesses of two optic nerve fiber layers (the peripapillary retinal nerve fiber layer [pRNFL] and the macular ganglion cell-inner plexiform layer [GCIP]) correlated with study participants’ scores on the Symbol Digit Modalities Test. This test assesses cognitive function.

The researchers also found that the thicknesses of those optic nerve fiber layers correlated with deep grey matter (DGM) volume. Grey matter is a type of brain tissue that is essential to a number of functions, including cognition, emotions, movement, and more. Research shows that DGM volume loss drives disability accumulation in MS.⁸

Further, baseline measures of the nerve fiber pRNFL was associated with a change in Expanded Disability Status Scale (EDSS) score from the start of the study to Week 96. Baseline measures of both nerve fibers pRNFL and GCIPL were associated with a change in Timed 25-Foot Walk distances over the course of the study, as well as in the 96-week percentage change in brain volume.

Why does identifying such correlations matter? For at least two reasons… First, the better that neurologists can understand how various components of MS “move in sync” with one another, the better they can understand the disease itself, and how to treat it.

Second, because OTC is a safe and easily performed test (patients rest their chin on a support and look into the lenses of a machine, just as they would with a regular eye exam) that can be completed in a few minutes, it provides an efficient way to gather considerable information about the current status and likely future course of secondary-progressive MS.

 

– Back to index –

 

Getting a good night’s sleep with MS: study finds no easy answers

From muscle spasms and worrisome thoughts, to bathroom runs and feeling too warm under the covers, people with MS face many obstacles to getting a good night’s sleep.

They also are pursuing many means of overcoming those obstacles, according to a recent study from Australia.⁹ Unfortunately, however, the study found that several of those strategies have significant downsides.

The study’s authors analyzed data on 1,590 people with MS who participate in the Australian MS Longitudinal Study. The people studied had an average age of 58.9 years and an average time since diagnosis of 17.0 years. Eighty percent were female. Researchers used an instrument called the Pittsburgh Sleep Quality Index (PSQI) to divide the participants into those with good sleep quality (n=474; 30% of the total group) and those with poor sleep quality (n=1,116; 70% of the total).

Compared to people with good sleep quality, those with poor sleep quality were more likely to pursue several approaches to enhance their sleep, as detailed in the table below.

Treatment types, %	People with good sleep quality	People with poor sleep quality
Any type of sleep treatment (medication or sleep hygiene practice)	52%	80%
Three or more sleep treatments	33%	50%
Sleep hygiene behaviors only	35%	24%
Medications only	6%	13%
Both sleep hygiene and medications	7%	38%

 

The sleep hygiene behaviors practiced most often by people with poor sleep quality were limiting caffeine use later in the day (41%), limiting fluid intake later in the day (29%), meditation or relaxation techniques (28%), exercise (24%), and limiting the use of electronic screens, such as those on computers, tablets, and phones (18%).

The medications used most frequently by study participants with poor sleep quality included sleeping tablets (22%), antidepressants (20%), melatonin (12%), and cannabis or related products (8%).

The researchers found that 52% of people in the study took medications that could affect sleep. Those medications, which in some cases may have been prescribed to promote better sleep and in other cases prescribed for different reasons, included antidepressants (38%), anti-spasticity medications/muscle relaxants (17%), benzodiazepines (8%), and narcotic analgesics (8%). The investigators’ analyses showed that people who took benzodiazepine had worse sleep quality than other people in the study, while those who took a widely prescribed class of antidepressants known as selective serotonin reuptake inhibitors had worse sleepiness during the daytime.

It’s hardly surprising that people with comparatively poor sleep quality would go to greater lengths than others to try to get a solid night of rest. At the same time, it’s discouraging that they remain in the “poor sleep quality” category despite those efforts. In fact, the study’s authors concluded, “Most prescription medications had no impact on sleep after adjusting for confounding [factors].”

This research examined a large population to help people with MS and their clinicians better understand a significant problem. The solution to that problem has to be found one person at a time, often through a process of trial and error and always in close consultation with an MS provider. As with so many efforts to enhance wellness and quality of life with multiple sclerosis, it begins with a conversation with one’s healthcare team.

 

– Back to index –

 

AI-driven analysis proposes new way to classify MS and its progression

After using artificial intelligence (AI) to analyze data on more than 8,000 people with multiple sclerosis, an international team of 22 experts has recommended a new approach to classifying MS progression across a spectrum of eight clinical states.¹⁰

In outlining the need to look at multiple sclerosis from a fresh perspective, the experts wrote, “Traditional classification of MS into distinct subtypes poorly reflects its pathobiology and has limited value for [predicting] disease evolution and treatment response, thereby hampering drug discovery.”

They added that while long-established terms such as relapsing-remitting MS, secondary-progressive MS, and primary-progressive MS have been useful in helping clinicians and patients discuss the disease and in designing clinical trials, “these traditional descriptors are based on clinical presentations of the disease rather than on the underlying disease biology.” They continued that while the current terms are considered mutually exclusive, “in reality, relapsing and progressive disease features often overlap.”

In developing their new approach to classifying MS, the researchers applied an AI method known as “bespoke probability machine learning.” They used the method to analyze information from the Novartis-Oxford MS database on 8,023 people with multiple sclerosis. Those people had participated in a Phase II or Phase III clinical trial of an MS medication.

At trial entry, 5,761 were classified as having relapsing-remitting multiple sclerosis (RRMS), while 1,550 had a diagnosis of secondary-progressive multiple sclerosis (SPMS) and 712 had been diagnosed with primary-progressive multiple sclerosis (PPMS). The database had up to 15 years’ worth of follow-up information on the patients.

The AI model’s analysis of data on those patients found four key dimensions of MS:

1. physical disability
2. changes in the brain
3. relapse rate
4. subclinical disease activity

Working within that framework, researchers used the model to identify eight clinical states of MS, ranging from early, mild, and evolving states at one end of the spectrum, to three advanced states at the other end. They also developed descriptions of the different clinical states of MS as demonstrated in the participating patients, and then outlined the probabilities for progression along the disease spectrum, according to the AI-driven data.

To test the validity of their approach, the experts replicated their results in an independent clinical trial dataset that had information on 2,243 people and in a 
real-world cohort of 2,080 people with MS.

What does this recommended new approach mean for people living with MS?

In the months ahead and probably even the next few years ahead, terms such as relapsing-remitting MS and primary-progressive MS will continue to be used in describing a diagnosis to a patient and determining which people with MS should be enrolled in a particular clinical trial.

However, the sheer volume of data analyzed in this study, the power of the AI methodology employed, and the prominence of the experts involved assure that this research will have a considerable impact on how clinicians think about MS. Combine those factors with many providers’ frustration with the way the current terminology does not adequately account for nuances and variations in how people experience multiple sclerosis, and this new classification system is likely to find a receptive audience.

By using AI to identify distinct clinical states of MS, along with patterns of movement from one clinical state to the other – as identified and charted by AI through data-driven analysis – this approach will hopefully allow people with MS and their clinicians to better understand a person’s current situation and likely future course, and to fashion comprehensive treatment plans accordingly.

 

– Back to index –

 

Using blood levels of a protein to gauge disease severity and predict treatment response

“Mind the gap,” railroad conductors say in urging passengers to watch their step as they move from a platform onto a train. Based on the results of recent research, MS clinicians may soon be telling themselves to “mind the GFAP” as they employ an emerging biomarker to assess and manage their patients’ multiple sclerosis.

Researchers recently examined data from two Phase III trials of the disease-modifying therapy Zeposia^® (ozanimod) to see what blood levels of a substance known as glial fibrillary acidic protein, or GFAP, could reveal about the severity of a person’s MS and expected outcomes on treatment.¹¹

GFAP provides structural support to astrocytes, specialized cells in the central nervous system (CNS) that nourish neurons and facilitate their function. The protein also helps to control the activity of CNS immune cells and to repair tissue in the brain and spinal cord.

When astrocytes are damaged due to conditions such as traumatic brain injury, Alzheimer’s disease, or MS, they release GFAP into the blood stream. Once scientists realized that elevated serum levels of the protein are an indicator of astrocyte damage, they began investigating how this information could help them better characterize the nature of a person’s MS and perhaps shape treatment plans.

In the Phase III SUNBEAM and RADIANCE trials, people with relapsing forms of MS received either ozanimod or an interferon-based disease-modifying therapy (DMT). In the first trial, study participants were treated for one year or longer, while the second study was 24 months in duration. In both trials, participants’ serum GFAP levels were measured at baseline, before they received medication.

The researchers first determined baseline GFAP levels and baseline participant characteristics, which included demographics (age, sex, and body mass index [BMI]), clinical characteristics (number of relapses in the previous year and EDSS scores), radiologic characteristics (number and types of lesions), as well as laboratory parameters (including blood levels of neurofilament light chain). The researchers then used statistical techniques known as “adjusted regression models,” to examine relationships between baseline GFAP levels and baseline participant characteristics to predict outcomes if taking a DMT.

They found that baseline GFAP had:

• Inverse associations with baseline body mass index (BMI) and whole brain volume (WBV); for example, lower GFAP levels in the blood were associated with a higher body mass index and greater whole brain volume

• An inverse association with whole brain volume when on treatment, meaning that a higher baseline serum GFAP level was associated with less whole brain volume on treatment
• Positive associations with (1) age, (2) blood levels of neurofilament light chain (which can indicate damage to the axons that project from the ends of neurons and convey electrical impulses from one neuron to another), (3) number of gadolinium-enhancing and T2 lesions seen on magnetic resonance imaging (MRI), and (4) Expanded Disability Status Scale (EDSS) score
• Positive associations with the number of relapses through Months 12 and 24 when taking a DMT, number of gadolinium-enhancing lesions at Month 12, number of new or enlarging T2 lesions over 12 months, and Month 12 EDSS score

In a different type of analytical model, baseline GFAP concentration independently predicted only the number of relapses through Month 12.


The study’s authors concluded, “These data suggest that plasma GFAP is a relapse-independent metric of baseline disease severity and a predictor of treatment response in participants with [relapsing MS].”

The study also shows how much research must be conducted to investigate a promising biomarker, validate its usefulness, and determine the significance of various findings or levels in different types of patients or clinical situations. While that work continues, the results of this and other studies suggest that clinicians eventually will have another reliable, easily obtained means of evaluating and treating their patients’ MS.

 

– Back to index –

 

Study demonstrates that Mavenclad^® reduces risk of conversion to MS after first demyelinating event

In a study of 227 people who experienced a first clinical demyelinating event, those who received the oral disease-modifying therapy (DMT) Mavenclad^® (cladribine) were less likely to convert to clinically definite multiple sclerosis (CDMS) than people who received placebo.¹²

After a median follow-up of 9.5 years, 52% of those treated with Mavenclad had gone on to CDMS. By comparison, 81% of placebo recipients were diagnosed with multiple sclerosis after a first demyelinating event, such as optic neuritis, balance problems, or numbness and tingling in a limb.

Further, time to CDMS was much longer in the Mavenclad group than in the placebo group – a median of 8.4 months versus 0.8 months. Additionally, relative to the placebo group, people with MS who received Mavenclad after their first event were less likely to be using a wheelchair or ambulatory device or to have received subsequent DMTs. Fifty-three percent of people in the Mavenclad group had not experienced a relapse, almost twice the proportion of people in the placebo group who were relapse-free (28%).

In 2018, the American Academy of Neurology (AAN) issued practice guideline recommendations supporting prescribing a DMT to a person with a single demyelinating event who was found to have two or more brain lesions characteristic of MS on magnetic resonance imaging and who wanted to start treatment after having received counseling on the risks and benefits of therapy.¹³

The study provides further evidence in support of that recommendation, which the AAN re-affirmed last year. ¹⁴

 

– Back to index –

 

Identifying the gut microbiome bacteria associated with the development of MS

Seventy percent or more of the body’s immune cells reside in the gut microbiome, the ecosystem of bacteria and other microbes that live and interact in the intestines. 
Researchers long have recognized that the composition of a person’s gut microbiome helps determine the risk for a wide range of diseases, including multiple sclerosis.

But which types of bacteria are most strongly associated with MS risk?

A team of researchers from Germany and the United States conducted an innovative, two-part experiment to help answer that question.¹⁵

First, they analyzed the mix of microbes found in the small intestines of 81 sets of monozygotic (identical) twins. In each case, one of the twins had MS while the other did not. The investigators explained that obtaining samples from the twins allowed them to “minimize confounding effects by genetic and early environmental factors.” The researchers identified 50 different, abundantly populated, types of microbes from this analysis.

Next, they took microorganisms from the small intestines of selected twins and transferred them orally into mice. They found that mice who received microbiota from a twin with multiple sclerosis subsequently developed MS-like disease at a much higher rate than mice who received microbes from a twin who did not have MS. Further analysis showed that two bacteria, Eisenbergiella tayi and Lachnoclostridium, were likely responsible for the increased incidence of the disease.


The researchers concluded that their work “may pave the way to functionally understand the role of gut microbiota in initiation of MS.” And because the composition of the gut microbiome is influenced in part by the food a person eats, studies such as this hold out the possibility of one day using diet to reduce MS risk and moderate the course of the disease. While that day is not on the near horizon, continued research may help speed its arrival.

 

– Back to index –

 

FDA extends review of tolebrutinib, an investigational medication for SPMS

The Food and Drug Administration (FDA) has extended its target action date for completing review of a new drug application (NDA) for the investigational MS medication tolebrutinib, according to Sanofi, the biopharmaceutical company developing the therapy.¹⁶

In a recent September 22nd press release, the company announced that the FDA had extended the date by three months as regulators review data supporting Sanofi’s application to approve tolebrutinib for use in treating non-relapsing, secondary-progressive multiple sclerosis (SPMS) in adults. The new target action date for an FDA decision is December 28, 2025.

Tolebrutinib belongs to a class of medications called Bruton’s tyrosine kinase inhibitors, or BTKis. These therapies work by blocking a protein – Bruton’s tyrosine kinase (BTK) – that plays a crucial role in the development and activation of B cells and microglia, two types of immune cells that have been implicated in the MS disease process. Inhibiting BTK is believed to diminish the pro-inflammatory effects of microglia that contribute to MS progression.

The Sanofi press release announcing the new date noted, “Based on the submission of additional analyses during the review, the FDA has determined that the additional information constituted a major amendment to the NDA and extended the target action date accordingly.” The press release also noted that, “Sanofi is confident in the potential positive impact tolebrutinib can provide and will continue to collaborate closely with the FDA during the review period.”

The company added that tolebrutinib was the first brain-penetrant BTK inhibitor in non-relapsing SPMS to be designated as a breakthrough therapy by the FDA. The FDA’s review is focused on data from the HERCULES and GEMINI 1 and 2 phase III studies evaluating tolebrutinib in people with non-relapsing SPMS and relapsing MS (RMS). Another phase III trial, PERSEUS, is evaluating tolebrutinib in primary-progressive MS. Sanofi said that the results of that study are anticipated later this year.

 

– Back to index –

 

References

1. Ruiz-Algueró M. Zhu, F, Chertcoff A, et al. Health care use before multiple sclerosis symptom onset. JAMA Netw Open. 2025;8;(8):e2524635. doi:10.1001/jamanetworkopen.2025.24635.
2. Al-Araji S, Moccia M, Jha A, et al. Effectiveness of disease-modifying therapies in patients with late-onset relapsing-remitting multiple sclerosis. Neurology. 2025. Aug 26;105(4):e213967.doi: 10.1212/WNL.0000000000213967.
3. Kazakou N-L, Bestard-Cuche N, Wagstaff LJ, et al. Metformin alters mitochondria-related metabolism and enhances human oligodendrocyte function. Nat Commun. 2025 Aug 30;16(1):8126. doi: 10.1038/s41467-025-63279-4.
4. Massot C, Guyot MA, Blanchard A, Norberciak L, Donze C. Effectiveness of aerobic treadmill training on walking distance in patients with multiple sclerosis with moderate disability: a randomised controlled multicentre trial. NeuroRehabilitation. 2025. 56(2):243-253. doi: 10.1177/10538135241306674.
5. Thouvenot E, Laplaud D, Lebrun-Frenay C, et al. for the D-LAY MS Investigators. High-dose vitamin D in clinically isolated syndrome typical of multiple sclerosis: the D-Lay MS randomized clinical trial. JAMA. 2025 Apr 22;333(16):1413-1422.doi: 10.1001/jama.2025.1604.
6. Gavoille A, Leray E, Marignier R, et al. for the OFSEP investigators. Sex-related gap in the use of disease-modifying therapies in multiple sclerosis. Neurology. 2025 Aug 26;105(4):e213907.doi: 10.1212/WNL.0000000000213907.
7. De Angelis F, Cameron JR, Eshagi A, et al. for the MS-SMART Trial investigators. Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial. J Neurol Neurosurg Psychiatry. 2025;96(7):647-654. doi: 10.1136/jnnp-2024-334801.
8. Eshaghi A, et al. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018 Feb;83(2):210-222. doi: 10.1002/ana.25145. Epub 2018 Feb 6. PMID: 29331092; PMCID: PMC5838522.
9. Jemere T, van der Mei I, Honan C, et al. Treatments used by people living with MS to get to sleep or stay asleep, and impacts on sleep quality and daytime sleepiness. Mult Scler Relat Disord. 2025 Sep:101:106565. doi: 10.1016/j.msard.2025.106565.
10. Ganjgahi H, Häring, DA, Aarden P, et al. AI-driven reclassification of multiple sclerosis progression. Nat Med. 2025.
11. Harris S, Comi G, Cree BAC, et al. Glial fibrillary acidic protein as a marker of disease in relapsing multiple sclerosis: post hoc analysis of phase 3 ozanimod trials. Eur J Neurol. 2025. Jun;32(6):e70222.doi: 10.1111/ene.70222.
12. Giovannoni G, Boyko A, Correale J, et al. Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort. Mult Scler. 
2025.31(1):44-58. doi: 10.1177/13524585241302170.
13. Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90:777-788. doi:10.1212/WNL.0000000000005347
14. Yoon H, Gerdes LA, Beigel F, Peters A. Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—an unbiased functional study. Proc Natl Acad Sci U S A. 2025. May 6;122(18):e2419689122.doi: 10.1073/pnas.2419689122.
15. American Academy of Neurology. AAN Summary of Practice Guidelines for Clinicians. Practice guideline recommendations: disease-modifying therapies for adults with multiple sclerosis. Available at https://www.aan.com/Guidelines/home/GuidelineDetail/898. Accessed September 13, 2025.
16. Sanofi. Update on the US regulatory review of tolebrutinib in non-relapsing, secondary progressive multiple sclerosis. September 22, 2025. Accessed September 23, 2024.

 

– Back to index –

 

For More Information

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.

Written by Tom Garry, Medical Writer
Reviewed by Dr. Barry Hendin, MSAA Chief Medical Officer
Edited by Susan Wells Courtney, MSAA Senior Writer

Medical details and study results provided in MSAA’s published materials are for informational purposes only and are not to be considered as treatment advice or recommendations. Readers are encouraged to consult a healthcare professional before making any changes to their current treatment regimen.