Latest developments in MS research:
- Read about the possible inclusion of the optic nerve as a fifth area among the diagnostic criteria of MS
- Know more about the predominant themes of 2023, an outstanding year for MS research
- Learn about the prehistoric origins of the elevated risk of MS in Northern Europe
These noteworthy MS news highlights and more are included in our recently published ECTRIMS Bulletins – a 30-day snapshot of global news and 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 and publication cycle, you’ll be sure to hear from us.
Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
The study extensively explores the prehistoric origins of the elevated genetic risk for multiple sclerosis among northern Europeans. The research teams used modern data from the UK Biobank, together with a large ancient-genome dataset from the Mesolithic to the Bronze Age, and new DNA samples, extracted from teeth or skulls of ancient individuals from Medieval and post-Medieval periods. Taken together, these datasets depict 10,000 years of history of European population. The authors investigated which regions in the genomes of contemporary white Europeans show significant ancestry compositions. Pastoralist ancestry was associated with an apparent positive selection pressure within the HLA region on chromosome 6, particularly in people of steppe ancestry. The genetic risk for MS became more and more frequent during the Bronze Age, around the time where steppe pastoralist populations migrated from central Asia to Europe – 5,000 years ago. These populations introduced in Europe changes in lifestyle and diet, which involved direct contact with domesticated animals and their consumption. These aspects, along with the higher population density, may have exposed people to new pathogens transmitted by animals. The new pathogen pressure may have driven a positive selection of variants, which are now associated with an increased risk for MS.
Multiple sclerosis in 2023: beyond the boundaries
Three interconnected themes defined an outstanding year for MS research in 2023. The International Advisory Committee on Clinical Trials in MS has proposed a new perspective on MS, viewing it as a continuum where inflammation and neurodegeneration are both present from the onset of the disease and evolve over time. This novel, mechanism-driven framework necessitates new biomarkers, which can be complementary and used in combination to understand and predict the course of the disease. The third crucial theme of 2023 concerned the necessity of starting therapeutic interventions as early as possible. In this regard, genetic research has been offering new directions and insights.
Toward identifying key mechanisms of progression in multiple sclerosis
In this review, the authors aim at identifying the most prominent mechanisms of progression in MS. There is accumulating evidence that progression independent of relapse activity (PIRA) starts in early stages of MS and becomes the prominent feature in later disease stages. Progressive MS represents an ongoing process of neurodegeneration, in which microglia and astrocytes play a pivotal role. Inflammatory and neurodegenerative processes are driven by different pathophysiological mechanisms. Despite the differences, these processes are closely intertwined and are present in all disease courses. Therefore, the major goal of forthcoming treatments for progressive MS should be to combine strategies that simultaneously address active and progressive disease.
Astrocyte signaling and interactions in Multiple Sclerosis
This review highlights the relevance of investigating the contribution of astrocytes, the predominant glial cell population in the central nervous system, to demyelination and myelin repair in MS. The findings discussed elucidate that in MS astrocytes lose critical homeostatic functions and gain neuroinflammatory functions that promote disease. These changes, indeed, affect the crosstalk of astrocytes and other cells of the central nervous system, such as oligodendrocytes and microglia. The literature suggests the possibility of mitigating MS progression with specific therapeutic interventions targeting astrocyte subtypes. Further studies are required to better understand the role of astrocytes in demyelination and remyelination and assess the potential risks of interventions targeting astrocytes in MS.
Adding the optic nerve in multiple sclerosis diagnostic criteria: A longitudinal, prospective, multicenter study
The inclusion of the optic nerve as a fifth area to demonstrate dissemination in space (DIS) among the diagnostic criteria of multiple sclerosis would improve their capacity to correctly identify people with MS. In this study, fewer cases of MS were missed when the optic nerve assessment was included among the DIS criteria. The modified DIS criteria showed a sensitivity of 92.5% compared to the 88.2% of the 2017 McDonald criteria. The study assessed 157 people with MS from five different centers in the MAGNIMS (European Magnetic Resonance Imaging for Multiple Sclerosis) network. The optic nerve was assessed with two out of the 3 following investigations: magnetic resonance (MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP). The specificity (i.e. the criteria’s ability to correctly screen as negative people who did not have MS) of the modified criteria was slightly lower compared to the current criteria (80% versus 86.5%) and the accuracy (i.e. the capacity to give a correct result) was similar (86.6% vs 86.5%).
Phase 1 clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis
Transplantation of human stem/progenitor cells (hNSCs) was reported to be feasible, safe, and tolerated in a group of 15 participants – aged between 38 and 57 – with secondary progressive multiple sclerosis, active and non-active. The authors of this one-year phase I clinical trial treated the patients with hNSCs and an immunosuppressive regime. They observed no death nor serious adverse event related to the treatment. None of the participants withdrew from the study. After 6 months, only one person developed a mild partial motor seizure, that was possibly related to MS. Patients did not experience clinical relapses. Overall, clinical and laboratory measures showed a substantial stability of the disease. Inflammatory activity captured by magnetic resonance imaging (MRI) did not change.
Patient-reported outcome parameters and disability worsening in progressive multiple sclerosis
Patients-reported outcome measurements (PROMs) are increasingly used in clinical practice and clinical trials following the recommendations of health authorities. The authors of the present study evaluated the contribution of PROMs in predicting disability and in differentiating patients with disability progression and those with stable progressive MS in two progressive multiple sclerosis (PMS) cohorts. The PROMs were evaluated longitudinally and included Beck depression inventory – II (BDI-II), multiple sclerosis impact scale -29 (MSIS – 29) and fatigue scale for motor and cognition (FSMC). Patients with disability progression reported worse depression, fatigue, and quality of life scores. Furthermore, the authors observed an association between worse scores indicating physical limitation and higher risk for progression. The study highlights the potential of PROMs to offer additional insights on disability progression.
Evaluating the effects of brain injury, disease and tasks on cognitive fatigue
The study explores cognitive fatigue (CF) – i.e. the mental exhaustion which results from cognitive effort – in 3 groups of participants: 31 with MS, 31 with traumatic brain injury (TBI) and 30 healthy controls. Cognitive fatigue was induced with two different tasks while acquiring data with functional magnetic resonance imaging (fMRI). When reporting the subjective perception of their mental fatigue, before starting the tasks – “how mentally fatigued are you right now?” – people with MS rated an intermediate level of CF compared to the other two groups (although the difference between MS and control group was not statistically significant). After completing the cognitive tasks, mental fatigue increased at the same rate across the three groups. When the three groups experienced more fatigue, they also took more time to respond to the tasks. The authors also observed a correlation between the activation of the caudate nucleus of the basal ganglia and thalamus and cognitive fatigue in the three groups. Higher sense of fatigue was associated across the groups with an increased activity of the thalamus and a decrease in activation of the caudate nucleus.