Latest developments in MS research:
1. Read about the stem cell-derived model of MS showing that increased cholesterol synthesis can cause neurotoxicity
2. Know more about the interplay between ageing and MS
3. Discover how early loss of grey matter volume can predict cognitive impairment
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
Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis
Cell Stem Cell | 7 November 2024
New results highlight an altered metabolic state in induced neural stem cells (iNSCs) derived from individuals with progressive multiple sclerosis (PMS).
Cellular metabolism plays a central role in the processes that lead to senescence and disease-associated mechanisms. An altered metabolic state is present in senescent induced neural stem cells derived from individuals with PMS. The senescent phenotype was strongly associated with inflammatory signaling, a hypermetabolic state, and the neurotoxic senescence-associated secretory phenotype (SASP). The PMS-derived iNSCs showed a significant accumulation of lipid droplets. This accumulation was mainly driven by HMGCR, an enzyme that plays a key role in the production of cholesterol. Increased activity of this enzyme in induced neural stem cells from individuals with PMS appears to regulate the SASP. Inhibiting HMGCR activity with simvastatin helped reduce neurotoxicity.
Cognitive Impairment & MS
Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study
Brain Communications | October 2024
Cognitive impairment occurring 20 years after an MS diagnosis is predicted by early loss of grey matter volume in certain brain regions, an Italian study shows.
This retrospective longitudinal study tracked 175 individuals with multiple sclerosis at the MS Centre of the Veneto Region. After 20 years of follow-up, 81 individuals experienced cognitive impairment. Reductions in grey matter volume in the precuneus, insula, parahippocampal gyrus, and cingulate within the first two years following an MS diagnosis were predictors of long-term cognitive impairment occurring 20 years later.
Aging and MS
The ageing central nervous system in multiple sclerosis: the imaging perspective
Brain | November 2024
This review critically and in-depth analyses the interplay between ageing and MS in the brain, focusing on avoiding misdiagnosis and monitoring treatment in older individuals.
Ageing induces immunological and pathological changes in the brain, which closely interact with MS clinical course. Magnetic resonance imaging (MRI) can offer valuable insights into the complex interplay between ageing and MS.
This review presents the current knowledge on senescence of the immune system and pathological mechanisms associated with aging. The clinical aspects of ageing in the central nervous system of individuals with MS are elucidated, including late onset, comorbidities, and diagnostic criteria in older individuals. 5-20% of individuals with MS have a late onset, with first symptoms starting after the age of 50. These individuals may experience more pronounced neurodegenerative processes and a greater cognitive impairment. Vascular comorbidities need to be considered especially in older individuals with MS. It is important to look for more than one periventricular lesion when making a diagnosis of MS especially in individuals with cerebrovascular risk factors.
Ageing can affect magnetic resonance measures, and its contribution must be disentangled when assessing older individuals with MS. Both ageing and MS can have closely intertwined effects on brain atrophy, iron abnormalities, and myelin changes in the central nervous system. These factors must be considered to minimise the risk of misdiagnosis and accurately assess treatment effects in individuals with MS.
Therapeutics
Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients
Multiple Sclerosis Journal | 4 November 2024
Wearing-off symptoms (WoSs) during treatment with natalizumab are not associated with changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels.
Wearing-off symptoms are MS-related symptoms that become more pronounced as the effect of treatment wears off just before the next infusion. These symptoms are reported by many individuals with MS under treatment with natalizumab. This longitudinal study analyses the levels of sNfL and sGFAP in 364 participants in the NEXT-MS trial, who received questionnaire about WoS at the start of the trial, after 1 year and 2 years. 55.5% individuals with MS during natalizumab treatment reported WoSs. Expanded Disability Status Scale (EDSS) scores were higher at baseline in individuals who experienced WoSs. No significant association was observed between sNfL or sGFAP concentration and occurrence of WoSs.
Directly isolated allogeneic virus–specific T cells in Progressive Multifocal Leukoencephalopathy
JAMA Neurology | October 2024
Treatment with DIAVIS T cells reduces mortality due to Progressive Multifocal Leukoencephalopathy (PML), new study shows.
Caused by John Cunningham (JC) polyomavirus, PML is an opportunistic brain infection leading to high mortality. PML can be associated with profound immunosuppression, mostly in the context of lymphoproliferative disorders or immunosuppressive treatments for autoimmune diseases. In rare cases, it has also been observed in people with MS treated with high-efficacy disease modifying therapies (DMTs). In this retrospective analysis – conducted at the Neurology Department of Hannover Medical School, Hannover, Germany – 28 individuals with confirmed PML were treated with DIAVIS T cells. Most of them were clinically severely impaired. None of the participants had MS. After the treatment, 22 individuals rapidly improved showing a reduction of viral load in the central nervous system, whereas 6 individuals quickly deteriorated and died. 20 patients survived beyond the 1 year follow up.
COMBAT-MS: A population-based observational cohort study addressing the benefit–risk balance of multiple sclerosis therapies compared with rituximab
Annals of Neurology | October 2024
Off-label rituximab is associated with lower rates of inflammatory activity but an increased rate of serious infections compared to other MS-approved treatments.
This nationwide observational study was conducted in Sweden across 10 university-affiliated MS centers. It involved a large, population-based cohort of 3,764 individuals aged 18 to 75 years diagnosed with relapsing-remitting MS. The study compared treatment with rituximab to natalizumab, dimethyl fumarate, fingolimod, and teriflunomide. No significant differences in disability worsening were observed between rituximab and the other approved treatments. The main differences emerged in the secondary endpoints at 3 and 5 years. Rituximab was associated with lower relapse rates. Notably, individuals who switched to rituximab from another treatment – but not those who initiated treatment with rituximab – had a higher risk of severe infections.
Hospital-treated infections and risk of disability worsening in Multiple Sclerosis
Annals of Neurology | October 2024
Rituximab increases risks of infections compared to interferon beta and glatiramer acetate, but reduces the risk of disability worsening associated with serious infections.
This cohort study on the Swedish MS Registry shows that compared with interferon beta and glatiramer acetate, rituximab increases the risk of serious infections. However, the magnitude of disability worsening related to serious infections was greater under treatment with interferon beta and glatiramer acetate.