The latest developments in MS research:
- Read about the organoids enriched by glial cells that can aid in research and treatment testing.
- Know more about the global strategies that may enhance MS research.
- Learn about the associations between different lipids and axonal damage and disease activity.
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.
Stem Cells and Therapeutics
A glia-enriched stem cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis
Cell Reports Medicine | 20 August 2024
A simplified platform replicates the human brain’s diverse cells and opens the door for testing new drugs to stop inflammatory neurodegeneration.
3D models of the human brain, known as organoids, were capable of self-organising and mimicking the complex makeup of the human brain. They contained human induced pluripotent stem cells (hiPSC), neurons, astrocytes, and oligodendroglia. Over an 8-week period, the organoids rapidly generated a diverse range of mature cells typical of the central nervous system.
When stimulated with inflamed cerebrospinal fluid from individuals with MS, the organoids – enriched by glial cells – accurately imitated the communication between cells usually seen in chronic active MS. The models replicated the specific patterns of cell behavior and damage associated with MS chronic inflammation. Remarkably, six days after the exposure, the number of oligodendrocytes was reduced by half.
Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis
Cell Stem Cell | 25 August 2024
Stem cell models are providing new insights into how glia cells contribute to MS and may reveal potential new targets for treatment.
Researchers from The New York Stem Cell Foundation (NYSCF) Research Institute and Case Western Reserve University studied the possible role of disfunctional glial cells in initiating MS and progression. They used induced pluripotent stem cell (iPSC) technology to investigate human glial cells in isolation, outside the brain. This approach allowed them to examine the cells’ behaviour without the interference of inflammation and immune cells.
The team generated 17 iPSC lines from individuals with various phenotypes of MS – relapsing-remitting, primary progressive and secondary progressive – and 5 iPSC lines from healthy individuals. The cells were enriched in astrocytes and oligodendrocyte lineage cells. Single-cell RNA sequencing of these glia-enriched coltures revealed intrinsec features of oligodendrocytes and astrocytes in individuals with MS. Notably, cultures derived from individuals with primary progressive MS showed fewer oligodendrocytes, a finding attributed to increased ferroptosis – a type of cell death resulting from the accumulation of iron.
Additionally, oligodendrocytes and astrocytes from individuals with MS exhibited higher levels of immune and inflammatory genes, similar to what is found in glia cells of deceased people with MS.
Future directions in MS research
The refined Pathways to Cures Research Roadmap for multiple sclerosis cures
Multiple Sclerosis Journal | 30 August 2024
Global Summit of 200 researchers and stakeholders in the MS field from 15 countries updated the Pathways to Cures Research Roadmap.
Stop, Restore, End are the three key pathways highlighted in the roadmap. The Stop pathway aims to achieve no new disease activity, the “Restore” pathway focuses on the recovery of neurological function, and the “End” pathway seeks to prevent the onset of new MS cases.
The objectives of the global summit include creating conditions for earlier and more accurate diagnosis and treatment, developing therapies for progressive MS, focusing on remyelination strategies, and preventing the onset of MS.
How can progress in MS research be accelerated? Lowering barriers on data sharing, collaborating and sharing clear priorities and equitable rules of engagement. Furthermore, the global MS community must sustain research funding to avoid delays and waste of resources, and ensure that new therapies are accessible to people with MS.
Engagement of individuals affected by MS can improve the quality, relevance and impact of MS research.
The first global landscape analysis of multiple sclerosis research funding
Multiple Sclerosis Journal | 31 July 2024
Stopping MS progression is considered a priority, new study shows.
The study identified 2,346 MS research projects, funded with a total of $1.5 billion by governmental and non-profit MS organisations from 2021 to 2023. Of these projects, 60% were categorised under the “Stop” umbrella, followed by 31% in “Restore” and 8% in “End”. The study highlights the need for global coordination in MS research. These insights can help guide investments in future shared research plans and focus on areas of critical need for individuals with MS.
Prioritising global strategies to cure MS
Multiple Sclerosis Journal | 30 August 2024
A shared global agenda is crucial for advancing MS research.
Global collaboration is essential to improving the lives of people with MS. Greater transparency in resource allocation is fundamental for alligning efforts and identifying new opportunities for cooperation. To achieve this, data-sharing agreements should be standardised. This would enable faster and more efficient data sharing across multiple institutions and countries, reducing administrative burdens.
The editorial also underscores the importance of continuous and stable funding to prevent abrupt interruptions of long-term studies. Furthermore, Europe and North America, which have the highest number of MS projects, should support economically disadvantaged countries to ensure equity in MS research.
Cognition and MS
Cognitive progression independent of relapse in multiple sclerosis
Multiple Sclerosis Journal | 28 August 2024
Cognitive decline can occur even in the absence of relapses and physical disability worsening, new study finds.
A retrospective study of 336 individuals with relapsing remitting MS (RRMS) revealed that nearly half (n= 167) experienced cognitive decline. Cognitive decline was predominantly attributed to progression independent of relapse activity (PIRA) rather than relapse-associated worsening (RAW). Furthermore, cognitive decline occurred independently of both relapses and the progression of physical disability. Notably, the authors found that cognitive PIRA occurred in individuals with RRMS regardless of whether they were undergoing therapy. However, these findings were predominantly observed in individuals receiving low-efficacy treatments. Cognitive PIRA was detected only when assessing individuals with MS with the whole Brief Cognitive Assessment for MS (BICAMS).
Cognitive function in severe progressive multiple sclerosis
Brain Communications | July 2024
New auditory test can help assessing cognitive issues in individuals with progressive severe MS, paving the way to better understanding cognitive decline in this population.
Conventional cognitive batteries are often challenging to administer in individuals with progressive severe MS, due to important motor, vision, and speech difficulties. The Auditory Test of Processing Speed (ATOPS) was used to evaluate attention and cognitive processing speed also in people with severe disabilites.
Findings indicated that individuals with MS who have an Expanded Disability Status Scale (EDSS) score between 7.0 and 9.5 show poorer cognitive performance across all cognitive domains compared to individuals with MS with EDSS scores between 3.00 and 6.5. Cognitive processing speed, learning and memory, and language resulted particularly affected.
Imaging and non-imaging biomarkers
Distinct plasma lipids predict axonal injury and multiple sclerosis activity
Journal of Neurology, Neurosurgery & Psychiatry | 12 September
Different groups of lipids indicate axonal damage and disease activity in individuals with MS.
Lipids are especially important in the study of neuroinflammation, as they are key components of myelin – the protective cover of nerve axons – and various lipid types modulate inflammation. The authors investigate the association between lipids and disease activity in children. This helps minimise the influence of other factors like comorbidities and prolonged environmental exposure, which could otherwise bias the results.
The study examined plasma samples of 435 children with MS from 17 US sites short after MS onset. Thanks to an in-depth lipidomics analysis, the authors observed a strong association between structural lipids, like phosphatidylcholines and phosphatidylethanolamines, and levels of neurofilament light chain (NfL). These specific lipids may indicate a cell membrane damage.
Moreover, another group of lipids, the polyunsaturated fatty acids (especially ω−3 and ω−6), was most commonly associated with reduced disease activity over time, demonstrating a protective effect.