Latest developments in MS research:
- Read about a new framework for guiding research on physical activity and MS
- Learn about early cortical remyelination in people with MS
- Know about the identification of independent neuropathological dimensions to disentangle the heterogeneity of MS
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.
Lifestyle and physical activity
Focusing on neural mechanisms of exercise training benefits in multiple sclerosis
Multiple Sclerosis and Related Disorders | June 2024
The present paper aims to propose a framework for guiding research on the effects of physical activity on mobility and cognition in multiple sclerosis (MS). It suggests four pathways within an experimental medicine framework: 1) developing a model by identifying potential targets in the central nervous system (CNS); 2) establishing associations between the conceptual model and cognitive and motor outcomes; 3) assessing the effects of exercise interventions on CNS outcomes; 4) conducting a comprehensive examination of the effects of physical training on motor and cognitive outcomes using the CNS targets as mediators. This approach could help provide more robust evidence to support the promotion of exercise training among healthcare providers for people with MS.
Pathogenesis
Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis
Journal of Neuroinflammation | 14 May 2024
Microglia and astrocytes play a crucial role in neuroinflammation associated with MS and contribute to alter the synaptic transmission by releasing proinflammatory cytokines. Interleukin-9 (IL-9) – a pleiotropic cytokine – is involved in MS pathophysiology. In individuals with relapsing-remitting MS, IL-9 levels in the cerebrospinal fluid (CSF) are inversely correlated with inflammation and neurodegeneration. The present study investigates the role of IL-9 in female mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. The authors observe that both systemic and local administration of IL-9 ameliorates EAE disease, significantly improving clinical disability and attenuating neuroinflammation and synaptic damage.
Neuropathology
Disentangling the heterogeneity of multiple sclerosis through identification of independent neuropathological dimensions
Acta Neuropathologica | 21 May 2024
The present study investigates the heterogeneity of lesion types in individuals with MS. Researchers analysed the data from 226 donors with MS in the Netherlands Brain Bank autopsy cohort. They identified three dimensions of MS neuropathology associated with clinical manifestations. Dimension 1 is associated with clinical severity and demyelination. Donors scoring high on Dimension 1 had more extensive pathology, neuroaxonal damage, more active and mixed lesions, more lesions with foamy microglia, and more severe disease. Dimension 2 is linked to less severe disease and the presence of nodules, which may be considered the first stage of lesion formation. Donors scoring high on Dimension 2 had a higher proportion of active lesions with ramified microglia. Interestingly, Dimension 2 is related to genetic risk in the HLA region. Dimension 3 is linked to a decreased lesion activity and to a higher proportion of mixed compared to active lesions. Donors scoring high on Dimension 3 had longer disease duration, ramified microglia morphology, more propensity to form scars, less involvement of the adaptive immune system, less axonal damage, and a higher axonal density. The three dimensions were not associated with age at onset, sex, or clinical phenotypes of MS. Considering the individual scores on these different dimensions can represent a starting point for further stratification of individuals with MS.
Review
Neurological efficacy and safety of mesenchymal stem cells (MSCs) therapy in people with multiple sclerosis (pwMS): An updated systematic review and meta-analysis
Multiple Sclerosis and Related Disorders| 14 May 2024
After analysing 30 studies, researchers found that individuals who received a specific type of stem cell treatment – intrathecal (IT) protocol-based transplantation of mesenchymal stem cells (MSCs) – showed a notable improvement in their expanded disability status scale (EDSS) in the short term compared to the group who received placebo. No difference was observed in the annual rate of relapses.
Therapeutics
Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis
The study investigates demyelination and remyelination in 140 people with all clinical phenotypes of MS for 5 years, using magnetization transfer imaging (MTI). As the disease progresses over time, cortical myelin loss increases. However, about half individuals with MS benefit from extensive spontaneous repair of cortical myelin, regardless of age and disease duration. Interestingly, the authors show that cortical remyelination prevents atrophy and long-term disability in individuals at early stages of MS and with limited cortical myelin loss.