Latest developments in MS research: Epstein-Barr virus as a cause of multiple sclerosis: opportunities for prevention and therapy; Gut Microbiota Changes during Dimethyl Fumarate Treatment in Patients with Multiple Sclerosis; Key Myelin Protein Shows Promise as Biomarker for MS
These noteworthy MS news highlights and more are included in our recently published ECTRIMS Bulletins – a 30-day snapshot of global news & publications on MS research, treatment and care.
ECTRIMS Bulletins can be sent to you every month, delivered straight to your inbox, via our free subscription service. Simply select all “topics” that are of interest to you, and when one of those appears in our news & publication cycle you’ll be sure to hear from us.
COVID-19
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News Medical | 7 February 2023
The safety of COVID-19 vaccines in healthy people and patients with autoimmunity or cardiac issues has been widely discussed. Clinical evidence indicates an increase in autoimmunity symptoms following COVID-19 vaccination, with mRNA and virus-vectored vaccines reported to trigger MS-like episodes. Adverse events after vaccination with either Pfizer’s or AstraZeneca’s vaccine have been reported in individuals with MS from Germany and the UK, with rheumatoid arthritis (RA) flares developing 12 hours after the second vaccine dose in one individual, and another team identifying new-onset RA within four weeks of vaccination.
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Pathogens | 2 February 2023
This review article provides an overview of the safety profile and the actual known adverse effects of COVID-19 vaccines in relationship to their mechanism of action. The use and safety of these vaccines in at-risk individuals, especially those with autoimmune diseases or with previously reported myocarditis, together with the general population, are examined. The real necessity of administering these products with unclear long-term effects to at-risk individuals with autoimmune conditions is considered, given the existence of available therapeutic interventions and the relatively lower aggressive nature of the new viral variants.
Clinical Diagnosis, Imaging and Biomarkers
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Levels of GFAP protein in blood may predict ‘silent progression’ of MS
MS News Today | 9 February 2023
Measuring levels of serum glial fibrillary acidic protein (GFAP) in blood can help to predict disability progression that occurs without relapses in individuals with MS. These findings from a new study may have “clinical implications for patient management and development of novel drugs,” the researchers wrote, noting the ongoing “lack of validated biomarkers for disability progression independent of relapse activity” in MS.
Hi-res MRI Scanners May Bring MS’s Effect on the Cerebellum Into View
MS News Today | 1 February 2023
Researchers have been able to image the cerebellum, the region of the brain that plays key roles in MS and other diseases, with greater clarity than ever before. This novel imaging approach, which used magnetic resonance imaging (MRI) scanners equipped with powerful magnets, may further reveal how the cerebellum is affected in MS and provide new markers for disease prognosis and treatments.
Key Myelin Protein Shows Promise as Biomarker for MS
MS News Today | 23 January 2023
A study has noted that the tiny sacs of cellular content released by the myelin-producing cells of the brain and spinal cord may be good biomarkers for the diagnosis and prognosis of MS. This research showed that levels of myelin basic protein in these sacs are significantly higher in individuals with MS than in healthy subjects. In addition, patients with a primary progressive disease course have increased levels compared with those with relapsing forms of MS.
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Episodic Facial Paresis—An Isolated Presenting Symptom of Multiple Sclerosis
JAMA Otolaryngology – Head and Neck Surgery | 9 February 2023
Facial nerve palsy is a distressing symptom for patients that results in functional and social deficits often without an evident cause. Acute onset and rapidly resolving neurological deficits are typically seen with seizure or ischaemia, whereas subacute onset and persistent deficits are seen in demyelinating disease. Prior cases have described persistent facial paresis as the herald symptom for MS; the current case reports an intermittent unilateral paresis in a young man ultimately diagnosed with MS.
JAMA Neurol | 6 February 2023
This cohort study of 355 individuals with MS and 259 healthy controls investigated whether serum glial fibrillary acidic protein (sGFAP) and/or neurofilament light chain (sNfL) concentrations are associated with, and prognostic for, disease progression in individuals with MS. Findings suggest that sGFAP is more strongly associated with disease progression in MS than sNfL, which may have implications in disease management and the development of novel therapeutics.
J Magn Reson Imaging | 28 January 2023
The detection of new and enlarged lesions in individuals with MS is required to monitor disease activity. The current study aimed to assess the accuracy of novel software for the detection of white matter lesions in 206 individuals with at least two follow-up MRI studies in the Swiss Multiple Sclerosis Cohort study. The novel software demonstrated similar sensitivity to existing protocols.
Radiology | 17 January 2023
The human cerebellum has a large, highly folded cortical sheet. Its visualization is important for various disorders, including MS. The aim of this study was to image the cerebellar cortex in less than 20 minutes, reconstruct the cerebellocortical surface, and extract cortical measures with use of motion-corrected, high-spatial-resolution 7.0-T MRI. The investigators demonstrated the feasibility of this novel approach and postulate that it might provide new prognostic information.
Int J Mol Sci | 3 January 2023
The aim of this study was to confirm whether the presence of protein components of myelin in sacs released by the central nervous system might be useful as diagnostic and prognostic biomarkers in MS. Although the findings from this pilot study are preliminary and require confirmation in a larger patient population, the authors conclude that myelin basic protein measured in blood samples obtained from individuals suspected of having MS could facilitate diagnosis.
Therapeutics
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Zeposia’s long-term use doesn’t affect heart health, Phase 3 trials show
MS News Today | 14 February 2023
Long-term use of Zeposia (ozanimod) did not adversely affect the heart of relapsing MS patients treated for one or two years in Phase 3 clinical trials, with no clinically significant changes in cardiac function reported. Data on people enrolled in the two studies were retrospectively evaluated, as the therapy can affect heart rate. A similar finding came from an analysis of a Zeposia trial in people with ulcerative colitis, an inflammatory bowel disease.
CNM-Au8 preserves white matter in RRMS patients’ brains: Phase 2 trial
MS News Today | 14 February 2023
Treatment with CNM-Au8, an experimental oral liquid therapy, led to statistically significant improvements in the health of connections between brain regions for individuals with stable relapsing-remitting MS (RRMS). The Phase 2 VISIONARY-MS trial (NCT03536559) tested CNM-Au8 against a placebo in adults with stable RRMS and symptoms affecting their vision.
TG Therapeutics | 14 February 2023
Two posters to be presented at the forthcoming Americas Committee for Treatment and research in Multiple Sclerosis (ACTRIMS) annual forum will highlight data from the ULTIMATE I (NCT03277261) and II (NCT03277248) Phase 3 trials evaluating BRIUMVI™ (ublituximab) in adult patients with relapsing forms of MS.
Cycle Pharma | 13 February 2023
Cycle Pharmaceuticals Ltd has announced the launch of TASCENSO ODT, an orally disintegrating tablet, which is its first product to treat individuals with MS in the US. This launch ensures individuals with MS in the US who currently benefit from Gilenya, or generic fingolimod, can access appropriate patient support services alongside the bioequivalent, non-generic, TASCENSO ODT. Gilenya patient support services are scheduled to be withdrawn on 31 March 2023.
Health Canada clears Phase 1 trial of Lucid-MS in healthy volunteers
MS News Today | 9 February 2023
FSD Pharma will soon launch a first-in-human trial in healthy volunteers testing Lucid-21-302, known as Lucid-MS, its novel chemical treatment for MS. In a press release, FSD Pharma announced that Health Canada has cleared the company to initiate a Phase 1 clinical trial of the investigational therapy.
Berberine, plant compound, eases disease severity in MS mouse model
MS News Today | 8 February 2023
Treatment with berberine, a compound found in many plants, eased disease severity and showed anti-inflammatory effects in a mouse model of MS. “These results confirmed that treatment with berberine efficiently improved the disease in the animal model of MS,” the researchers wrote, noting that the results suggest this compound may be a promising therapeutic approach for individuals with MS.
Mayzent, vitamin D combo alleviates MS signs in mouse study
MS News Today | 6 February 2023
Using Mayzent (siponimod) and vitamin D3 as a combination therapy was found to improve motor function and promote remyelination in a mouse model of MS. Potential synergistic effects of vitamin D3 and Mayzent were demonstrated in this model, leading the authors to conclude that the use of this combination regimen to treat individuals with MS may represent a novel strategy to accelerate remyelination, alleviate disease symptoms and improve quality of life.
Rewind’s Remyelinating Therapy Pipeline Backed by New Investments
MS News Today | 31 January 2023
Rewind Therapeutics has received new investments to support the development of its therapeutic candidates designed to promote remyelination in neurodegenerative diseases, including MS. Currently, the company is focused on advancing its lead candidate toward the clinic as it continues to build a pipeline of additional candidate remyelination molecules. Rewind’s approach is to ensure the correct functioning of oligodendrocyte precursor cells and oligodendrocytes, the cells required for myelin production in the central nervous system.
LAPIX, FDA Meeting Sets Way for LPX-TI641 Clinical Development
MS News Today | 30 January 2023
Lapix Therapeutics has met with the US Food and Drug Administration (FDA) to determine how to advance its investigational treatment candidate LPX-TI641 into clinical trials for autoimmune diseases such as MS. The outcome of the pre-investigational new drug meeting request supports Lapix’s plan to develop a path forward to the clinic for LPX-TI641. LPX-TI641 is an orally available small molecule that has been designed to restore immune tolerance, a process that can be disrupted in autoimmune diseases such as MS.
Fractalkine Found to Promote Remyelination in MS Mouse Model
MS News Today | 27 January 2023
The signalling protein fractalkine was found to promote the repair of myelin damaged by the mistaken immune attack that leads to MS. In an animal model of the disease, the molecule triggered both the growth of new myelin-producing cells and the reduction of pro-inflammatory immune cells in the brain. This led to more effective remyelination, suggesting that fractalkine may be a novel therapeutic candidate for reversing myelin damage and potentially slowing or halting MS progression.
Patient Dosing Starts in MS Phase 2 Clinical Trial of Oral SAR443820
MS News Today | 26 January 2023
Patient dosing has begun in a Phase 2 trial testing Denali Therapeutics‘ investigational oral receptor-interacting protein kinase 1 (RIPK1) inhibitor SAR443820 in individuals with MS. RIPK1 is an enzyme that potentiates inflammation and nerve cell death in the central nervous system. The clinical trial (NCT05630547) seeks to enroll about 168 patients, age 18–60 years, with either relapsing-remitting MS, active and non-active secondary progressive, or primary progressive MS. Recruitment is ongoing at sites in China and Europe.
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Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model
Stem Cell Reports | 14 February 2023
Damage or loss of myelin and oligodendrocytes are the principal mechanisms underlying demyelination in individuals with MS. In this murine MS model infusion of fractalkine was shown to increase the formation of oligodendrocytes and thus enhance remyelination within the central nervous system.
JAMA Neurol. | 13 February 2023
This recently published review article provides an overview of Bruton tyrosine kinase (BTK) inhibitors as a novel B-cell-directed therapeutic approach in MS. The authors conclude that, although the novel approach of targeting BTK is highly promising, several questions remain unanswered, such as the long-term effects of using BTK inhibitors in the treatment of inflammatory central nervous system (CNS) disease. Questions also remain regarding the place of BTK inhibitors in the MS treatment algorithm, including their ability to cross the blood–brain barrier, and the optimal sequencing of therapies after anti-CD20 treatment.
Gut Microbiota Changes during Dimethyl Fumarate Treatment in Patients with Multiple Sclerosis.
Int J Mol Sci. | 1 February 2023
The gut microbiota is involved in the development of the immune system and can modulate the risk for immune-mediated disorders such as MS. Dysbiosis has been demonstrated in individuals with MS and its restoration by disease-modifying therapies has been hypothesised. The findings of this study suggest that the gut microbiota may be involved in the therapeutic action and side effects of dimethyl fumarate, representing a potential target for improving disease course and disease-modifying therapy tolerability.
J Comp Eff Res | 27 January 2023
This study investigated the relative costs and benefits of cladribine and dimethyl fumarate for the treatment of relapsing-remitting MS from the perspective of the Spanish National Health Service. Cladribine was shown to be both less costly and more effective than dimethyl fumarate. This study may therefore provide important evidence for policymakers, budget holders and health advisors when making treatment decisions for individuals with relapsing-remitting MS.
Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis.
Neurol Neuroimmunol Neuroinflamm | 26 January 2023
The long-term effects of ocrelizumab treatment on immune cell subsets and B-cell regulatory factors in individuals with MS were investigated for up to 2.5 years in this study. The changes noted indicate persistently decreased B-cells and CD20+ T-cells following ocrelizumab treatment, alongside alterations in regulatory factors and their associated receptors.
JAMA Neurol | 23 January 2023
The findings from the Antelope (NCT04115488) Phase 3 clinical trial comparing the efficacy of biosimilar natalizumab (PB006) with reference drug in patients with relapsing-remitting MS have been recently published. PB006 is the first biosimilar monoclonal antibody developed for MS treatment and was shown to match the efficacy, safety and immunogenicity of reference natalizumab, thus providing an alternative treatment for individuals with relapsing-remitting MS.
Front Behav Neurosci | January 2023
Remyelination is key to alleviating the symptoms associated with MS and preventing further neuronal damage. This study used a toxin-induced mouse model to assess whether combined treatment with vitamin D3 and Siponimod could enhance remyelination. The findings from the study showed improvement in behavioural deficits and significant promotion of remyelination, which may ultimately assist in guiding treatment recommendations for individuals with MS.
Immun Inflamm Dis | January 2023
This study tested the anti-inflammatory effects of the alkaloid, berberine, in an experimental animal model of MS. Inflammation was seen to decrease significantly in mice treated with berberine, with associated effects on the expansion of certain immune cells. The investigators concluded that berberine appeared to have a protective effect on disease development and status in an experimental MS model.
Pathology
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‘Mini-brain’ models point to poorer oligodendrocyte growth in PPMS
MS News Today | 13 February 2023
Using stem cells derived from individuals with MS, researchers have developed cerebral organoids or “mini-brains” to better study the cellular and molecular mechanisms leading to this neurodegenerative disorder. Initial analysis showed that patient-derived stem cells, especially those from people with primary progressive MS, tend to be less able to grow into myelin-making cells called oligodendrocytes.
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Epstein-Barr virus as a cause of multiple sclerosis: opportunities for prevention and therapy
Lancet Neurology | 7 February 2023
Mounting evidence from different fields of research supports the pivotal role of the Epstein-Barr virus (EBV) in the development of MS. Ongoing research is trying to clarify whether EBV causes neuroinflammation via autoimmunity or antiviral immunity, and if the interaction of EBV with genetic susceptibility to MS can explain why a ubiquitous virus promotes immune dysfunction in susceptible individuals. If EBV also has a role in driving disease activity, the characterisation of this role will help diagnosis, prognosis and treatment in individuals with MS. Ongoing clinical trials targeting EBV and new anti-EBV vaccines provide hope for future treatments and preventive interventions.
Biology Open | 6 February 2023
This study used brain models derived from the stem cells of healthy control subjects, together with individuals with primary progressive MS, secondary progressive MS or relapsing remitting MS to investigate the pathological basis of the varied clinical phenotypes of MS. Findings include that the genetic background of an individual can directly alter stem cell function providing new insights into the cellular dysregulation that occurs in MS. In addition, the pathway associated with the cell cycle inhibitor p21 may provide a potential new target for therapeutic strategies in MS.
How does neurovascular unit dysfunction contribute to multiple sclerosis?
Neurobiol Dis. | 1 February2023
This review article revisits MS risk factors and MS pathophysiology, with the aim of highlighting the known and potential roles of neurovascular unit dysfunction in MS development and disease progression. The neurovascular unit consists of a group of cells, closely related to each other, including neurones, astrocytes, endothelial cells of the blood-brain barrier, myoctyes, pericytes and extracellular matrix components. The suitability of the neurovascular unit as a potential target for future disease-modifying therapies for MS is also evaluated.
Tumefactive multiple sclerosis presents with painless progressive hemiparesis and aphasia.
Lancet | 21 January 2023
Tumefactive MS is a rare diagnosis which can be difficult to distinguish from high-grade gliomas. The authors present a case study of a 20-year-old male presenting in the emergency department with progressive, painless paralysis of the right arm and leg that had commenced approximately 48 hours earlier. Investigations resulted in a diagnosis of tumefactive MS and, following treatment, the patient has experienced no relapses.
Differential Diagnosis
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Primary progressive MS confirmed as own disorder in mouse study
MS News Today | 7 February 2023
Primary progressive multiple sclerosis (PPMS) is driven by antibodies in the cerebrospinal fluid, but this is not the case in the more common relapsing forms of MS. Researchers say that this finding will have far-reaching impact in the treatment of PPMS versus other types of MS.
Publications
Appl Neuropsychol Adult. | 11 February 2023
This study examined the relationships among functional outcomes and performance on standard-length and abbreviated cognitive screening measures for MS. The findings extend prior research showing that abbreviated tests of processing speed and immediate recall can provide unique predictive information regarding objective functional outcome.
Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic
Brain | 3 February 2023
There is currently a lack of understanding as to whether primary progressive MS and relapsing remitting MS represent a single pathological disease or two distinct disease entities with the common pathological feature of inflammatory demyelination. In this study the investigators demonstrate that cerebrospinal fluid from individuals with primary progressive MS is unique in its ability to induce motor disability and spinal cord pathology including demyelination and neurodegeneration in a mouse model of MS. These findings may have implications for the development of treatments for individuals with primary progressive MS.
Int Immunopharmacol. | 2 February 2023
Tolerance failure is implicated in the development of several autoimmune disorders, including MS. In individuals with secondary progressive MS (SPMS), a decrease in the frequency of the CD4+CD25+FOXP3+Helios+ regulatory T-cell (Treg) population can result in an imbalanced immune system. Thus, one of the immunological mechanisms underlying this disease may be a deficiency in Tregs. Helios gene expression was also decreased in these patients, which may exacerbate functional defects in Tregs.
Nursing and Care Management
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Dietician advice assists MS patients improve calcium intake: Trial
MS News Today | 13 February 2023
A tailored diet plan from a dietician may help people with MS ingest more calcium from foods, which could make their bones stronger and less prone to osteoporosis, according to findings from a recent study. The CalciCoach (NCT02664623) clinical study compared the amount of dietary calcium consumed by individuals with MS who received three sessions of personalised advice from a dietician with that consumed among those who received nutritional advice from a leaflet.
New remote monitoring system to be tested in MS patients in rehab
MS News Today | 10 February 2023
Datos Health, a remote care automation company, is collaborating with the Shirley Ryan AbilityLab in Illinois on a study that will gauge the effectiveness of remote therapy monitoring in patients with various conditions and disorders, including MS. “The research study will allow us to determine the feasibility of remote therapeutic monitoring for clinicians and patients alike,” said Miriam Rafferty, PhD, director of implementation science at Shirley Ryan.
Older MS patients with stable disease may safely stop DMTs: Study
MS News Today | 10 February 2023
People over 60 years old with MS who have stable disease may discontinue their disease-modifying treatments (DMTs) without an added risk of relapses or worsening disability, according to a small study. At that age, only the presence of lesions with active inflammation and an Expanded Disability Status Scale (EDSS) score above 3, indicating at least moderate disability, were significant predictors of a greater risk of relapses or disability progression.
Sesh, MS Canada partner to help MS patients with mental health
MS News Today | 6 February 2023
To support the wellness journeys of Canadians living with MS, digital healthcare company Sesh is partnering with MS Canada to provide free, unlimited access to its online mental health platform. The partnership allows patients to participate in virtual therapist-led support groups, and kickstarts research efforts around MS and mental health.
MS Cognitive Problems Can Ease With Rehab, Mindfulness Training
MS News Today | 1 February 2023
A clinical trial has shown that two alternative treatments may help to alleviate the cognitive challenges which individuals with MS can face in daily life. Patients randomised to either cognitive rehabilitation therapy (CRT) or mindfulness-based cognitive therapy (MBCT) in the REMIND-MS study had fewer complaints about their cognition, although most benefits were lost within 6 months of the sessions ending.
Aging MS Patients Are Focus of UT Dell Medical School Initiative
MS News Today | 31 January 2023
A team of scientists at the University of Texas at Austin Dell Medical School are working to establish best practices for managing MS in older adults, citing a relative lack of research on the disease in people older than 50 years. The Healthy Aging with MS research initiative and clinical programme will seek to create a multidisciplinary clinic and collaborative care model that focuses on older patients’ needs.
Insufficient and Poor Sleep in Teen Years Increase Risk of MS: Study
MS News Today | 26 January 2023
Teenagers with poor sleep quality or insufficient sleep, that is <7 hours a night, are 40% to 50% more likely to develop MS later in life than those who get adequate rest, according to a Swedish population-based study. The authors concluded that sufficient restorative sleep, needed for adequate immune functioning, may thus be another preventive factor against MS.
Fewer Women with MS Choosing to Stop DMT Use While Pregnant
MS News Today | 25 January 2023
The use of DMTs by pregnant women with MS has significantly increased over the last decade or so, with fewer women stopping treatment before giving birth, according to the findings from a single-centre study in Italy. While most patients (95.1%) discontinued a DMT while pregnant between 2005 and 2012, more than half (53%) of those who became pregnant between 2013 and 2020 continued using their therapy, without greater risks to the mother or child.
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Clin Neurol Neurosurg | 23 January 2023
This observational study aimed to compare outcomes between older individuals (>60 years) with MS who had been stable on therapy for at least 2 years before discontinuing DMTs, and those who continued on therapy. The authors noted no increased risk of relapse, or worsening of disability, in patients who discontinued DMTs, concluding that there may be limited effect of continued immunomodulation in older individuals with MS who have stable disease.
Journal of Neurology, Neurosurgery and Psychiatry | 23 January 2023
Shift work is often associated with sleep deprivation and circadian desynchrony, and has been associated with an increased risk of MS. This Swedish population-based case-control study aimed to examine the impact of sleep duration, circadian disruption and sleep quality on MS risk. The authors noted that compared with sleeping 7–9 hours/night during adolescence, short sleep (<7 hours/night) was associated with increased risk of developing MS as was subjective low sleep quality during adolescence. Sufficient restorative sleep at a young age is needed for adequate immune functioning and may be a preventive factor against MS.
Mult Scler Relat Disord | 20 January 2023
Pregnancy planning is a relevant issue in the management of MS in women of childbearing age. This article reviewed data from a single centre collected over 15 years to describe how pregnancy planning and management for women with MS have changed over time. This study concluded that DMTs are more frequently used in women of childbearing age, even during pregnancy, leading to a reduced annualised relapse rate both before and after delivery and an absence of increased obstetric complications.