Current Treatment Options in Neurology, Год журнала: 2024, Номер 27(1)
Опубликована: Окт. 31, 2024
Язык: Английский
Journal of Neuroimmunology, Год журнала: 2024, Номер 391, С. 578368 - 578368
Опубликована: Май 14, 2024
Язык: Английский
Процитировано
4
Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)
Опубликована: Окт. 10, 2024
Multiple sclerosis (MS) is a complex chronic neuroinflammatory disease characterized by demyelination leading to neuronal dysfunction and neurodegeneration manifested various neurological impairments. The endocannabinoid system (ECS) lipid signalling network, which plays multiple roles in the central nervous periphery, including synaptic signal transmission modulation of inflammation. ECS has been identified as potential target for development novel therapeutic interventions MS patients. It remains unclear whether ECS-associated metabolites are changed could serve biomarkers blood or cerebrospinal fluid (CSF). In this retrospective study we applied targeted lipidomics matching CSF serum samples 74 80 non-neuroinflammatory control We found that MS-associated lipidomic changes overall did not coincide between serum. While glucocorticoids correlated positively, only (eCB) 2-arachidonoyl glycerol (2-AG) showed weak positive correlation (r = 0.3, p < 0.05) Peptide endocannabinoids be quantified first time but differ controls. patients elevated levels prostaglandin E2 steaorylethanolamide serum, 2-oleoylglycerol cortisol CSF. Sex-specific differences were showing increased 2-AG males only. Overall, arachidonic acid was males. Interestingly, eCBs positively with age due young relapsing-remitting Our findings reveal significant discrepancies underscoring measuring matrices optimal detecting system. sex age-specific analytes stress axis specifically supports role may relevant drug strategies.
Язык: Английский
Процитировано
4
Journal of Neurochemistry, Год журнала: 2025, Номер 169(1)
Опубликована: Янв. 1, 2025
ABSTRACT Aging is the most common risk factor for Multiple Sclerosis (MS) disease progression. Cellular senescence, irreversible state of cell cycle arrest, main driver aging and has been found to accumulate prematurely in neurodegenerative diseases, including Alzheimer's Parkinson's disease. senescence central nervous system MS patients recently gained attention, with several studies providing evidence that demyelination induces cellular hallmarks p16INK4A p21 expression, oxidative stress, senescence‐associated secreted factors. Here we discuss current animal models different glial populations system, highlighting major gaps field still remain. As premature may exacerbate inflammation, resulting inhibition myelin repair, it critical increase understanding vivo, functional effects on cells, impact removing senescent cells remyelination MS. This emerging holds promise opening new avenues treatment patients. image
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Март 21, 2025
Approximately 50% diagnosed with relapsing-remitting multiple sclerosis (RRMS) transition to secondary progressive (SPMS) within 20 years following disease onset. However, early diagnosis of SPMS and effective treatment remain important clinical challenges. The lack established diagnostic criteria often leads delays in identifying SPMS. Also, there are limited disease-modifying therapies (DMTs) available for forms MS, these require evidence activity be initiated. This review examines the challenges diagnosing at an stage summarizes current potential use biomarkers progression practice. We also discuss difficulties initiating DMTs indicated active (aSPMS), particularly patients already undergoing that suppress activity, which may mask presence inflammatory required therapy switch. article addresses both non-active SPMS, along trials supported approval aSPMS or relapsing MS Europe, includes aSPMS. offer insights on when discontinuing treatments appropriate.
Язык: Английский
Процитировано
0
Annals of Clinical and Translational Neurology, Год журнала: 2024, Номер 11(2), С. 450 - 465
Опубликована: Янв. 10, 2024
Abstract Objective Repeated intravenous administration of anti‐CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions people with MS (pwMS). Methods We studied pwMS treated de‐novo RTX ( n = 7) OCR 8). The examinations were scheduled before initiation therapy and every 12 weeks for up 15 months. Immunophenotyping subsets blood was performed by multiparametric fluorescence cytometry. Results A significant, persistent decrease CD19 + B cells observed already first infusion p < 0.0001). significant proportional reduction memory within B‐cell pool achieved only after two cycles 0.005). a increase immature 0.04) naive 0.004), again second cycle. As T‐cell pool, continuous T helper (TH) cells/central TH 0.02/ 0.008), while number regulatory (Treg) decreased 0.007). percentage dependent TH17.1 central dropped cycle 0.02). No differences between found. Interpretation Peripheral profiling revealed more differentiated insights into prompt delayed immunological effects repeated treatment. observation changes some pathogenetically relevant deserves further attention.
Язык: Английский
Процитировано
3
GeroScience, Год журнала: 2024, Номер unknown
Опубликована: Сен. 23, 2024
Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder characterized by the development of neutralizing autoantibodies (inhibitors) against coagulation factor VIII (FVIII). This review provides an in-depth exploration AHA, covering its epidemiology, pathogenesis, clinical presentation, diagnosis, complications, and treatment strategies, focusing on recent advancements. AHA can manifest in both men women with no prior history. The annual incidence estimated to be approximately 1 case per million individuals general population. increases significantly age: among aged 60 years or older 3 4 cases year. Typically, patients present acquired that isolated, prolonged activated partial thromboplastin time stemming from FVIII deficiency. Diagnosis relies detection antibodies using Nijmegen-modified Bethesda assay. Hemostatic control strategies involve bypassing agents like recombinant VII, prothrombin complex concentrate, porcine for patients. Emicizumab, novel agent, exhibits several potential advantages. In realm immunosuppressive inhibitor eradication, CyDRi regimen emerged as remarkable advancement, enhancing outlook management even elderly frail
Язык: Английский
Процитировано
3
Biochemical Pharmacology, Год журнала: 2024, Номер unknown, С. 116595 - 116595
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
3
Current Opinion in Neurology, Год журнала: 2024, Номер 37(3), С. 220 - 227
Опубликована: Апрель 3, 2024
The aim of this review was to examine the evidence for disease-modifying therapies (DMTs) discontinuation in older people with multiple sclerosis (MS). We first summarized aging-associated biological changes that influence MS progression and DMT effectiveness, then recent evaluating clinical outcomes discontinuing DMTs MS.
Язык: Английский
Процитировано
2
Neurology and Therapy, Год журнала: 2024, Номер 13(3), С. 519 - 533
Опубликована: Апрель 8, 2024
The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. efficacy disease-modifying therapies (DMTs) for RMS declines age. Also, older persons MS may be more susceptible to infections, hospitalisations and malignancy. Aging have higher rates comorbidities versus aged-matched controls, increasing the individual risk disability. We review therapeutic properties cladribine tablets (CladT) in RMS, regard their utility allowing these individuals cease continuous administration a DMT (i.e. act as an "exit therapy"). CladT thought immune reconstitution therapy, that two short courses oral treatment 1 year apart provide suppression disease activity responders far outlasts duration post-treatment reductions lymphocyte counts. Post hoc analyses, long-term follow-up populations randomised trials, real-world evidence suggest probably independent age, although data elderly are still needed. No clear adverse signals lymphopenia or other safety emerged immunosenescence setting age-related "inflammaging" predispose patients infections. Updating vaccination status recommended, especially against pneumococci herpes zoster patients, minimise useful alternative who often bear burden polypharmacy exposed effects immunosuppressive therapy.
Язык: Английский
Процитировано
2
Current Neurology and Neuroscience Reports, Год журнала: 2024, Номер 24(9), С. 341 - 353
Опубликована: Июль 12, 2024
Язык: Английский
Процитировано
2