Purpose Of Review: Degeneration of axons and their cell bodies is thought to occur progressively from the onset of multiple sclerosis and to be a significant cause of increasing disability. The mechanisms of neurodegeneration are becoming clearer and this work has already indicated potential molecular targets for therapeutic intervention to prevent neuronal injury. Attention is being directed at the appropriate design of clinical trials to test neuroprotection as a major strategy for the management of multiple sclerosis. The subtype of multiple sclerosis, the primary outcome measure and other detailed design issues remain controversial. This review considers the rationale for different therapeutic strategies for neuroprotection and discusses the controversies of trial design.
Recent Findings: The experimental work on neuroprotection in animal models of inflammatory axonal degeneration and consideration of outcome measurement in multiple sclerosis have developed sufficiently to enable trials of neuroprotection to be planned, powered and implemented. Trials assessing neuroprotection with tetrahydrocannabinol and lamotrigine are imminent; both will involve subjects with progressive forms of multiple sclerosis.
Summary: These advances mean that neuroprotection is emerging as a potentially important strategy for preventing disability in multiple sclerosis. It is likely that a range of neuroprotective strategies will be tested alone and in combination in future trials, and that trial design will be refined as experience accumulates.
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http://dx.doi.org/10.1097/01.wco.0000227034.85576.16 | DOI Listing |
Clin Immunol
January 2025
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, China. Electronic address:
The imbalance between Tregs and proinflammatory Th17 cells in children with biliary atresia (BA) causes immune damage to cholangiocytes. Dimethyl fumarate (DMF), an immunomodulatory drug, regulates the Treg/Th17 balance in diseases like multiple sclerosis (MS). This study explores DMF's effect on Treg/Th17 balance in BA and its potential mechanism.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Neurology, International University of Health and Welfare, Narita, Japan.
Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.
Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.
Biomed Pharmacother
January 2025
Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA; Department of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA. Electronic address:
There is currently no cure or disease-modifying treatment for post-traumatic osteoarthritis (PTOA). This study aims to assess the efficacy of dimethyl fumarate (DMF), a US-FDA approved drug for multiple sclerosis, as a treatment for PTOA. PTOA was induced in male Lewis rats by medial meniscal transection (MMT) surgery, and DMF was intra-articularly administered once, one week following surgery.
View Article and Find Full Text PDFMult Scler Relat Disord
January 2025
Multiple Sclerosis Center of Excellence West, Veterans Affairs, USA; Rehabilitation Care Service, VA Puget Sound Health Care System, 1660 S Columbian Way, Seattle, Washington, 98108, USA; Department of Rehabilitation Medicine, University of Washington, 325 9th Avenue, Seattle, Washington, 98104, USA. Electronic address:
Background/objective: Identifying research priorities of Veterans, MS researchers, and key stakeholders is critical to advance high-quality, evidence-based, and Veteran-specific MS care.
Methods: We used a modified Delphi approach to identify research priorities for Veterans with MS. Electronic surveys were distributed to Veterans with MS (n = 50,975), MS researchers (n = 191), VA healthcare providers (1,337), and funding agency representatives (n = 6) asking about their 2-3 most important research questions that would benefit Veterans with MS for researchers to answer in the next 5-10 years.
Front Biosci (Landmark Ed)
January 2025
The First College of Clinical Medical Science, China Three Gorges University, 443000 Yichang, Hubei, China.
Multiple sclerosis (MS) is a chronic autoimmune disorder marked by neuroinflammation, demyelination, and neuronal damage. Recent advancements highlight a novel interaction between iron-dependent cell death, known as ferroptosis, and gut microbiota, which may significantly influences the pathophysiology of MS. Ferroptosis, driven by lipid peroxidation and tightly linked to iron metabolism, is a pivotal contributor to the oxidative stress observed in MS.
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