Latest developments in MS research:
1. Read about the twin study that has identified early dysregulation of CD8+ T cells in MS.
2. Know more about the energy the brain of individuals with MS needs to switch between different states.
3. Learn more about the cluster of Tyzzerella nexilis that is enriched in progressive MS and may promote neuroinflammation.
These noteworthy MS news highlights and more are included in our recently published ECTRIMS Research Updates – a 30-day snapshot of global news and publications on MS research, treatment, and care.
ECTRIMS Research Updates 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 and publication cycle, you’ll be sure to hear from us.
Genetics
Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis
Science Immunology | 27 September 2024
CD8+T cell phenotype with enhanced activation, higher migratory potential and proinflammatory capacity was identified in both cotwins with subclinical neuroinflammation and individuals with MS.
The study leveraged the MS TWIN STUDY cohort, which involves a large group of monozygotic twins where only one twin has MS. The authors selected 12 twin pairs, in which one twin has MS, 6 cotwins are healthy and 6 have a subclinical neuroinflammation (SCNI). Thanks to in-depth immunological and metabolic single-cell analyses of peripheral CD8+ T cells, the authors observed transcriptional features of CD8+ T associated with MS in both cotwins with SCNI and individuals with MS. Brain tissues data, obtained from publicly available datasets, validated the persistence of these pathological signatures within MS lesions. Infiltrating CD8+ T have a proinflammatory role that may drive the disease already in early, prodromal stages.
Tyzzerella nexilis strains enriched in mobile genetic elements are involved in progressive multiple sclerosis
Cell Reports | 27 September 2024
A distinct cluster of Tyzzerella nexilis enriched in progressive MS may promote neuroinflammation.
This study identifies Tyzzerella nexilis, Ruthenibacterium lactatiformans, and Oscillibacter sp. as taxa enriched in progressive MS. In particular, the abundance of the bacterium Tyzzerella nexilis was associated with neurological disability and negatively correlated with brain volume. Importantly, a specific cluster of T. nexilis, characterised by many mobile genetic elements (MGEs), was enriched in individuals with secondary progressive MS. Specific genes of this cluster were linked to sulfate reduction and flagella formation. Mice that were mono-colonised with MGE-enriched T. nexilis were more likely to develop experimental autoimmune encephalomyelitis. This distinct cluster of T. nexilis may have the potential to promote neuroinflammation.
Clinical Trials
Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials
The Lancet Neurology | September 2024
These phase-3 clinical trials do not support the use of evobrutinib in individuals with relapsing MS.
Two phase-3 clinical trials, conducted at 701 MS centres and neurology clinics across 52 countries, compared the safety and efficacy of evobrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, versus teriflunomide, all taken orally. It included participants aged 18 to 55 years old with relapsing multiple sclerosis. The primary outcome of the trials was the reduction of the yearly relapse rate, but evobrutinib was not more effective than teriflunomide. It was also not superior to teriflunomide for the secondary outcomes, such as reducing disability and imaging measures of focal inflammation in the central nervous system. At week 12, the concentrations of serum neurofilament light chain (NfL) were slightly lower in individuals taking evobrutinib versus those taking teriflunomide in one trial. But these differences disappeared by week 96.
Evobrutinib was generally well tolerated. The most common adverse events were COVID-19, headache, and temporary increases in liver aminotransferase. Elevations in liver aminotransferase to more than 5 times the upper limit of normal (ULN) were more common with evobrutinib, especially in the first 12 weeks, and were completely normalised after discontinuation. These findings do not support the use of evobrutinib in individuals with relapsing MS.
Cognition & MS
Energy associated with dynamic network changes in patients with multiple sclerosis and cognitive impairment
Neurology | 12 November 2024
Switching between different brain states costs more energy in individuals with MS and cognitive impairment, new study shows.
Our brain is in different states while doing different activities, such as moving, perceiving the external world, paying attention, and resting or focusing on internal world – thoughts, memories, future plans. We switch from one state to another several times during the day. This study shows that individuals with MS who have a cognitive impairment switch between states less frequently than those with preserved cognitive function. Individuals with a cognitive impairment tend to spend more time in the “default mode network” state – engaged at rest or during moments of self-directed thinking – and less in the “visual network state”. Furthermore, they require more control energy to make these transitions.
Women’s Health
Topical review: Lactation and use of DMTs in women with MS
Multiple Sclerosis Journal | 20 August 2024
There is a need for further studies to inform decision-making on postpartum treatment for women with MS.
Breastfeeding, along with starting effective treatments early, can likely help lower the risk of rebound inflammatory activity after childbirth. Breastfeeding is associated with lower risk of relapses soon after giving birth, with an even greater benefit seen in mothers who exclusively breastfeed. Data on transfer of disease-modifying treatment (DMT) into breastmilk are still limited.
This article reviews the current research on how each DMT passes into breastmilk, its effects on infants, and the guidelines for using these treatments while breastfeeding. Overall, the available data suggest that first-line injectables, such as interferon beta and glatiramer acetate, and monoclonal antibodies, such as antiCD20 or natalizumab, can be considered safe during pregnancy and breastfeeding. Data are lacking for ofatumumbab, ublituximab, and alemtuzumab. In contrast, oral medications should be avoided while breastfeeding.
Comorbidities
Multiple sclerosis and cancer: Navigating a dual diagnosis
Multiple Sclerosis Journal | 30 September 2024
What are challenges when treating individuals with both MS and cancer?
So far, most studies indicate that DMTs have minimal to no effect on the risk of cancer. However, since individuals with MS now live as long as the general population, their risk of developing cancer may increase with age. Effectively managing the MS treatment and cancer immunotherapy requires close collaboration between oncologists and neurologists, to ensure individuals with MS are closely monitored with regular check-ups and scans. More studies are needed to understand the impact of cancer treatment and decisions on how to manage MS treatment on clinical outcomes for individuals with MS.
NMOSD and MOGAD
Quality of life in patients with myelin oligodendrocyte glycoprotein antibody associated disease compared to patients with AQP4-IgG positive neuromyelitis optica spectrum disorders: A Korean multicenter study
Multiple Sclerosis and Related Disorders | November 2024
Overall quality of life is similar between individuals with MOGAD and NMOSD.
This multicenter study compared the quality of life of 41 individuals with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and 78 with neuromyelitis optica spectrum disorder (NMOSD) from 10 hospitals in South Korea. The overall quality of life was similar between individuals with MOGAD and NMOSD. They both experienced at a similar level sleep disorders, fatigue and depression.