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ECTRIMS Bulletin: March 2023


min read

Latest developments in MS research: new study may help explain protective effects of pregnancy in MS; astrocyte receptors may help to ease MS cognitive issues; and a large; 10-year study has investigated the use of fingolimod in a real-world setting in MS patients.

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.


Clinical

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Study may help explain protective effects of pregnancy in MS

MS News Today | 8 March 2023 (as published in Clinical Epigenetics | 10 February 2023)

A new study of women with MS who had previously given birth may have identified one of the mechanisms behind the lasting protective effects of pregnancy seen in MS patients. Patients who’d had children were found to have a number of differences in methylation, a type of DNA modification, compared with their counterparts who had never been pregnant. Many of the affected genes were related to nerve cell development and function. The authors stated that, “Based on these findings, we believe that pregnancy-induced differences in DNA methylation could underlie the long-term protective effect of pregnancy in women with MS.”

ACTRIMS 2023: High-dose vitamin D doesn’t reduce MS activity: Trial

MS News Today | 3 March 2023

Taking high-dose vitamin D supplements as an add-on to standard MS treatment doesn’t reduce the risk of inflammatory disease activity for people with relapsing-remitting multiple sclerosis (RRMS), according to data from a clinical trial. The authors noted that these findings “suggest that prescribing higher doses of vitamin D for purposes of modifying the RRMS disease course may not be beneficial”.

ACTRIMS 2023: Documentary offers hope for the black MS community

MS News Today | 2 March 2023

MS has long been considered a disease that mostly affects white women. However, data from the US indicate that black people, particularly black women, may be more likely to develop the neurodegenerative disease than people of other racial and ethnic backgrounds. This misunderstanding can lead to misdiagnoses, gaps in care, under-representation in clinical trials, and an overall lack of visibility in the MS community. The “MS in Black and African Americans” documentary explores the experiences of black patients living with MS, highlighting the health inequities they face and ways to address them.

ACTRIMS 2023: HIV-positive people found to be less likely to develop MS

MS News Today | 1 March 2023

People infected with the human immunodeficiency virus (HIV), including HIV-positive individuals who received antiretroviral treatment at some point after infection, are significantly less likely to develop MS. The decrease in MS risk was particularly pronounced among HIV-positive women. Findings from this international cohort study suggest that HIV infection may protect against the development of the neurodegenerative disorder, particularly in female patients.

 

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Cognitive rehabilitation in multiple sclerosis: Three digital ingredients to address current and future priorities

Front Hum Neurosci. | 23 February 2023

This review article considers the cognitive impairments experienced by individuals with MS and the difficulties in daily living that these may cause. Current advanced technologies that may play a role in cognitive rehabilitation are described and the use of digital twin technology to address cognitive impairments in a large number of individuals with MS is proposed.


Pathogenesis

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ACTRIMS 2023: Astrocyte receptors may help to ease MS cognitive issues

MS News Today | 28 February 2023

Recent research suggests that activating certain receptors on astrocytes may offer a way of treating cognitive problems in individuals in MS. MS mouse models genetically engineered to lack tumour necrosis factor receptors (TNFR2) showed signs of greater cognitive problems, whereas cognitive gains were evident in mice with higher-than-normal receptor levels. Additional experiments are underway to further validate these findings, the researchers noted, with an ultimate goal of “explor[ing] the potential of TNFR2 as a therapeutic target for counteracting cognitive dysfunction in MS.”

ACTRIMS 2023: Loss of myelin in spinal cord tied to MS disability

MS News Today | 27 February 2023

Data from a new study using an advanced magnetic resonance imaging (MRI) technique called magnetisation transfer ratio (MTR) to assesses overall myelin integrity were presented at ACTRIMS 2023. The investigators demonstrated that a greater loss of myelin in the part of the spinal cord found in the neck was associated with worse disability in individuals with MS. More substantial myelin loss in the cervical spinal cord was also associated with declines in motor function and dexterity. Myelin loss was particularly evident in patients with primary progressive MS (PPMS), which is characterised by steadily worsening symptoms over time.

 ACTRIMS 2023: ‘Bacteria X’ in gut microbiome may drive inflammation

MS News Today | 27 February 2023

A certain bacterial species is enriched in the gut of people with secondary progressive MS (SPMS) and may promote neuroinflammation and drive disability progression in these patients, a study found. When isolated from SPMS patients and given to a mouse model, this strain of gut bacteria led to more pronounced neurological disability and increased numbers of immune cells directly implicated in the inflammation that drives MS.

  

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Early derangement of axonal mitochondria occurs in a mouse model of progressive but not relapsing-remitting multiple sclerosis

Neurobiology of Disease | March 2023

This study examined whether changes that occur in the functioning of mitochondria, the organelles responsible for cellular energy production, in individuals with MS are a driving factor in the evolution of MS, or occur later following nerve cell damage. Using mouse models of progressive MS and relapsing-remitting MS (RRMS) the investigators demonstrated that changes in mitochondrial function occur prior to the emergence of symptoms in progressive MS. Therefore, early mitochondrial dysfunction may be central to the neuropathogenesis of this type of MS.

Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case-control study.

J Neurol | 16 February 2023

Disease- and treatment-associated immune system abnormalities may confer a higher risk of COVID-19 in individuals with MS. This study aimed to assess modifiable risk factors associated with COVID-19 in individuals with MS. At multiple logistic regression, higher levels of vitamin D emerged as a protective factor against COVID-19. In contrast, a higher number of cohabitants and work requiring direct external contact, or in the healthcare sector, resulted in increased risk of infection with COVID-19.


Imaging and Non-Imaging Biomarkers

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Icobrain MS, an AI tool for assessing MRI scans, being tested in UK

MS News Today | 9 March 2023

An upcoming study will investigate how well Icobrain MS, an artificial intelligence-based technology, can interpret magnetic resonance imaging (MRI) data from people with MS and how its use might influence patient care. The project, called AssistMS and led by Icometrix and Queen Mary University of London, ultimately aims to improve MS care. The study lead investigator noted that “If successful, AssistMS will have a significant impact on [MS patients’] quality of life, as well as equity and efficiency of MS care across the UK.”

 

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Visually Evoked Potential as Prognostic Biomarker for Neuroaxonal Damage in Multiple Sclerosis From a Multicenter Longitudinal Cohort

Neurol Neuroimmunol Neuroinflamm. | 6 March 2023

With the increasing use of visually evoked potentials (VEPs) as quantitative outcome parameters for myelin in clinical trials, an in-depth understanding of longitudinal VEP latency changes and their prognostic potential for subsequent neuronal loss is required. This longitudinal multicentre study evaluated the association and prognostic potential of VEP latency for retinal neurodegeneration, measured by optical coherence tomography (OCT), in relapsing-remitting MS (RRMS).

Association of Serum Neurofilament Light Chain Levels at Disease Onset With Disability Worsening in Patients With a First Demyelinating Multiple Sclerosis Event Not Treated With High-Efficacy Drugs

JAMA Neurology | 27 February 2023

In this multicentre cohort study, serum neurofilament light chain (sNfL) levels were assessed in 578 individuals with MS within 12 months of disease onset. The investigators examined any association between sNfL levels and long-term worsening of disability, and concluded that high sNfL levels within the first year of MS were predictive for disability worsening. It is possible, therefore, that sNfL level measurement may help identify optimal candidates for highly effective disease-modifying treatments.

Genetically determined serum serine level has a novel causal effect on multiple sclerosis risk and predicts disability progression

J Neurol Neurosurg Psychiatry | 2 February 2023

This study used Mendelian randomisation methods to assess the potential causal relationship of 174 metabolites with MS. Genetic scores for identified causal metabolite(s) were then computed to predict MS disability progression in an independent longitudinal cohort. A novel genetic causal effect of serine on MS onset was noted, such that individuals whose serine level is 1 standard deviation above the population mean will have 1.67 times the risk of developing MS. These findings support investigating serine as an important candidate biomarker for MS onset and disability progression.


Therapeutics

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ACTRIMS 2023: GA Depot found to ease MS disability in Phase 3 trial

MS News Today | 7 March 2023

GA Depot, an experimental, long-acting version of glatiramer acetate, significantly reduced relapse rates and prevented the development of new lesions among people with relapsing forms of MS, according to new data from a Phase 3 clinical trial (NCT04121221). Disability levels were also significantly reduced with the treatment, given via monthly injections, as compared with placebo. According to researchers, these findings suggest that GA Depot may serve as a more convenient alternative to an approved version of glatiramer acetate that is given either once daily or three times per week via subcutaneous injections.

ACTRIMS 2023: RRMS treatment may ‘give patients a better choice’

MS News Today | 7 March 2023

New data from the EMPhASIS Phase 2 trial (NCT03846219) and its open-label extension, testing vidofludimus calcium, a novel oral treatment candidate for relapsing-remitting multiple sclerosis (RRMS), show promising safety and efficacy. The therapy was found to safely reduce brain lesions and prevent disability progression in most people with RRMS. For a population that often faces a choice between efficacy or safety when it comes to selecting a disease-modifying therapy, vidofludimus calcium may prove an effective and well tolerated treatment option.

Intermittent fasting for 8 weeks shows benefits in MS in pilot study

MS News Today | 22 February 2023 (as published in Front. Neurol | 12 January 2023)

An eight-week intermittent fasting intervention for individuals with relapsing-remitting MS (RRMS) led to significant improvements in cognition and manual dexterity. Patients also tended to have lower fatigue and pain scores at the programme’s end, an exploratory study showed. Importantly, according to researchers, participants stuck with the intervention, showing high levels of adherence and acceptability to the time-restricted eating plan.

 

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Towards equitable access to treatment for multiple sclerosis

Lancet Neurol | March 2023

This editorial notes inequalities in access to treatments for MS around the world and reports how on Dec 11, 2022, the Multiple Sclerosis International Federation (MSIF) applied to the World Health Organization (WHO) requesting the addition of disease-modifying treatments for MS to their Model List of Essential Medicines. Approval by WHO of the MSIF application will be a crucial first step to ensure that people with MS around the world will be able to access appropriate treatment options.

A decade of fingolimod in multiple sclerosis: Insights from a large real-world cohort study.

Rev Neurol (Paris) | 23 February 2023

This study analysed baseline characteristics and clinical evolution of 1227 patients with relapsing-remitting MS (RRMS) treated with fingolimod from 2010 to 2019 in four French MS referral centres. According to authors, findings of this large cohort study confirm the durable reduction in annualised relapse rate (ARR) described in the pivotal studies of fingolimod. Switching from a moderate-efficacy disease-modifying therapy (DMT) to fingolimod decreased the relapse risk; although switching from high-efficacy DMT increased the risk of relapse, the overall 5-year ARR remained stable.