Latest developments in MS research: two new studies offer fresh insights on how clinicians may be able to use biomarkers to monitor and predict multiple sclerosis (MS) activity and disability; researchers find a bacterial toxin in the gut may be a key environmental MS driver.
These noteworthy MS news highlights and more are included in our recently published ECTRIMS Bulletins – a 30-day snapshot of global news & publications on MS research, treatment and care.
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Clinical
Family planning considerations in people with multiple sclerosis
MS is frequently diagnosed in individuals who are planning on having children. Although MS itself does not negatively influence most pregnancy outcomes, less is known about the effects of foetal exposure to novel disease-modifying therapies (DMTs). Moreover, the withdrawal of some DMTs during pregnancy can modify the natural history of MS, resulting in a substantial risk of pregnancy-related relapse and disability. This review article focuses on the role of emerging research in guiding decision-making in women with MS and discusses how future advances will require regular updating of recommendations.
Pathogenesis
Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting
Neuroimmune interactions between glial, neural and immune cells play important roles in MS pathology and offer potential targets for therapeutic intervention. This article reviews underlying risk factors, mechanisms of MS pathogenesis and available disease-modifying therapies, and examines the value of emerging technologies, which may address unmet clinical needs and identify novel therapeutic targets.
Bacterial toxin epsilon in gut may be environmental driver of MS
J Clin Investigation | 28 February 2023
A bacterial toxin in the gut, specifically the epsilon toxin produced by Clostridium perfringens bacteria in the intestinal tract, may be a key environmental driver of MS. After finding the toxin at a higher abundance in the faecal samples of MS patients compared with healthy people, scientists determined that epsilon was capable of producing MS symptoms in mice predisposed to the disease.
Imaging and Non-Imaging Biomarkers
Challenges and Opportunities for the Promising Biomarker Blood Neurofilament Light Chain
The field of biomarkers has witnessed significant advances in the last decade with the introduction of new, highly sensitive tests to measure central nervous system-derived proteins in the blood. One of the most studied biomarkers is neurofilament light chain (NfL), a cytoskeleton protein proposed to be a robust marker of neurodegeneration. With increased analytical capacity to measure its levels in the blood, NfL has emerged as a promising marker of real-time disease activity and treatment response in MS. Indeed, NfL has been proposed to be the neurological equivalent of an established inflammation marker, C-reactive protein. However, the application of NfL measurement as a tool for clinical decision-making and research still faces barriers due to gaps in knowledge about the biology behind NfL release in the blood, factors influencing NfL concentration, and their correct interpretation in health and disease.
Early MS MRI markers linked to worse disability in 10 years time
Neuroradiol J. | 6 February 2023
A newly published study has suggested that magnetic resonance imaging (MRI) scans of the brain acquired early after the onset of MS may help predict disease severity and disability accumulation after 10 years. In particular, two MRI biomarkers (inter-caudate diameter [ICD] and third ventricular width [TVW]) detected in imaging scans were significantly linked to worse long-term disability. However, the authors noted that despite the statistical significance of these measures, their clinical utility may not be reliable.
Therapeutics
Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome
Annals of Neurology | March 2023
The radiologically isolated syndrome (RIS) represents the earliest detectable pre-clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in preventing first symptom manifestation at this stage in the disease spectrum.
Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing-remitting multiple sclerosis patients: a monocentric longitudinal observational study.
Cladribine is approved for the treatment of active relapsing remitting MS (RRMS), but its positioning in MS therapeutic scenarios still needs to be fully elucidated. This monocentric, observational, real-world study of RRMS patients treated with cladribine assessed magnetic resonance imaging (MRI) activity and disability worsening. Cladribine was shown to be more effective when positioned early in the treatment algorithm. Real-world data on larger populations with longer follow-up are needed to confirm these findings.
Higher blood levels of ocrelizumab lower confirmed disability progression risk
Neurol, Neuroimmunol, Neuroinflammation | 15 February 2023
Analysis of data from three Phase 3 clinical trials suggests that higher blood levels of ocrelizumab are associated with a significantly lower risk of confirmed disability progression during treatment in people with relapsing and progressive forms of MS. Notably, the lower disability progression rates reported in people with higher ocrelizumab exposure were independent of reductions in relapse rates or magnetic resonance imaging (MRI) activity, suggesting the medication worked to prevent progression independent of relapse activity (PIRA).