CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(21)

Опубликована: Сен. 7, 2023

CD8+ T cells outnumber CD4+ in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally expanded effectors are unknown. Based on evidence that demyelination is necessary not sufficient for progression MS, we previously hypothesized CNS-infiltrating specific neuronal antigens directly drive axonal injury leads to cumulative neurologic disability patients MS. We now show induced expression MHC class I neurons axons resulted presentation a neuron-specific neoantigen (synapsin promoter–driven chicken ovalbumin) antigen-specific (anti-ovalbumin OT-I TCR-transgenic cells). These neuroantigen-specific surveilled CNS absence were retained. However, upon induction via cuprizone intoxication, proliferated, accumulated CNS, damaged neoantigen-expressing axons. further report elevated β2-microglobulin transcripts protein gray matter white tracts tissue from findings support autoreactive anti-axonal anti-neuronal MS progression.

Язык: Английский

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Study protocol: effects of exercise booster sessions on preservation of exercise-induced adaptations in persons with multiple sclerosis, a multicentre randomised controlled trial—the MS BOOSTER trial

BMJ Open, Год журнала: 2024, Номер 14(8), С. e085241 - e085241

Опубликована: Авг. 1, 2024

Multiple sclerosis (MS) causes a broad range of symptoms, with physical function being one the most disabling consequences according to patients themselves. Exercise effectively improves lower extremity function. Nonetheless, it is unknown which exercise modality effective and remains challenging keep persons MS adhering over longer period. Therefore, present study aims investigate how booster sessions (EBS) influence sustainability exercise-induced effects on function, furthermore, (aerobic training or resistance training) in terms improving

Язык: Английский

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Navigating a Paradigm Shift in the Treatment of CNS Demyelinating Diseases in a Middle-Income Country

Multiple Sclerosis and Related Disorders, Год журнала: 2025, Номер unknown, С. 106544 - 106544

Опубликована: Май 1, 2025

Язык: Английский

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The Multiple Sclerosis Health Resource Utilization Survey (MS-HRS): Development and Validation Study

Journal of Medical Internet Research, Год журнала: 2020, Номер 22(3), С. e17921 - e17921

Опубликована: Фев. 19, 2020

Survey-based studies are frequently used to describe the economic impact of multiple sclerosis (MS). However, there is no validated health resource survey available, preventing comparison study results and meaningful conclusions regarding efficiency long-term treatments.The aim this was develop validate a tablet- paper-based MS utilization survey.We developed Multiple Sclerosis Health Resource Utilization Survey (MS-HRS), consisting 24 cost items for paper tablet users. Data validation came from two large German observational studies. practicability assessed according response rate. Reliability described using test-retest reliability as well Guttman lambda. Construct validity convergent discriminant via correlations with associated patient-reported outcomes known-group analyses.In total, 2207 out 2388 (response rate: 92.4%) patients completed were included determine psychometric properties. The had an intraclass correlation coefficient 0.828 over course 3 months. Convergent analyses showed that total costs correlated positively increased disability (r=0.411, P<.001). For validity, Treatment Satisfaction Questionnaire Medication ranged -0.006 (convenience) -0.216 (effectiveness). mean annual €28,203 (SD €14,808) (US $39,203; SD US $20,583) disease-modifying therapies.The MS-HRS multilingual, reliable, valid, electronically easy-to-administer questionnaire providing holistic cross-sectional longitudinal assessment in MS.

Язык: Английский

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Gaining First Insights on Secondary Progressive Multiple Sclerosis Patients Treated With Siponimod in Clinical Routine: Protocol of the Noninterventional Study AMASIA

JMIR Research Protocols, Год журнала: 2020, Номер 9(7), С. e19598 - e19598

Опубликована: Июнь 4, 2020

A high proportion of patients with relapsing remitting multiple sclerosis convert to secondary progressive (SPMS) characterized by irreversibly progressing disability and cognitive decline. Siponimod (Mayzent), a selective sphingosine-1-phosphate receptor modulator, was recently approved the European Medicines Agency for treatment adult SPMS active disease, as evidenced relapses or magnetic resonance imaging features ongoing inflammatory activity. Approval Food Drug Administration covers broader range indications, comprising clinically isolated syndrome, sclerosis, SPMS. However, effects siponimod have not been assessed in structured setting clinical routine so far.The objectives AMASIA (impAct Mayzent [siponimod] on secondAry Sclerosis long-term non-Interventional study GermAny), prospective noninterventional study, are assess effectiveness safety evaluate impact disease burden quality life socioeconomic conditions. Here, we report design AMASIA.Treatment will be evaluated 1500 during 3-year observational phase. According genetic polymorphism CYP2C9, initial dose titrated maintenance 1 mg (CYP2C9*1*3 *2*3) 2 (all other polymorphisms CYP2C9 except *3*3, which is contraindicated) taken orally once daily. Primary endpoint 6-month confirmed progression, functional composite Expanded Disability Status Scale symbol digit modalities test take appropriate account changes increase sensitivity. Further measures including activity data; assessments domains; questionnaires addressing patients', physicians', relatives' perspectives progression; worsening; life; aspects documented using documentation system MSDS3D.AMASIA being conducted between February 2020 2025 up 250 neurological centers Germany.AMASIA complement pivotal phase III-derived efficacy profile real-world data further several individual such conditions caregivers. It might help establish promising option routine.DERR1-10.2196/19598.

Язык: Английский

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Gender disparities in health resource utilization in patients with relapsing–remitting multiple sclerosis: a prospective longitudinal real-world study with more than 2000 patients

Therapeutic Advances in Neurological Disorders, Год журнала: 2020, Номер 13

Опубликована: Янв. 1, 2020

Background: For the case of multiple sclerosis, research on gender differences from a health economics perspective has not received much attention. However, cost-of-illness analyses can provide valuable information about diverse impact disease and thus help decision-makers to allocate scarce resources. The aim this study was describe healthcare resource use associated societal costs perspective. In particular, we aimed identify how utilization potentially differs in certain cost components between men women. Methods: Clinical economic data were extracted two prospective, multicentre, non-interventional, observational studies Germany. Information obtained all patients quarterly basis using validated questionnaire. Cost conducted including direct (healthcare-related) indirect (work-related) costs, regardless who bears them. Gender-related analysed by multivariable generalized linear model with negative binomial distribution log link function due right-skewed pattern data. addition, for women descriptively within subgroups two-year activity. Results: total, 2095 (women-to-men ratio 2.7:1) presented mean age 41.85 years median Expanded Disability Status Scale 2 (interquartile range 1–3.5) ( p > 0.30 gender-related differences). Women did statistically differ total (€2329 ± €2570 versus €2361 €2612). both, higher advancing severity main driver. Regarding healthcare-related resources, incurred ambulant consultations [incidence rate (IRR) 1.16, confidence interval (CI) 1.04–1.31], complementary medicine (IRR 2.41, CI 1.14–5.06), medical consumables 2.53, 1.69–3.79) informal care 2.79, 1.56–5.01). Among found presenteeism 0.62; 0.53–0.72) disability pension 1.62; 1.23–2.13). Conclusions: Multiple sclerosis poses significant burden patients, families society. While male female specific items that are similar those wider non-MS population.

Язык: Английский

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Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

Journal of Clinical Medicine, Год журнала: 2021, Номер 10(4), С. 868 - 868

Опубликована: Фев. 19, 2021

The aim of the study was to verify association clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments Poland. Disability defined as relapse-associated worsening (RAW), independent relapse (PIRA), MRI Activity (PIRMA). Data from Therapeutic Program Monitoring System were analyzed. Three panels identified: R0, no during treatment, R1 R2 occurrence first second year respectively. In R0 panel, we detected 4.6% PIRA at 24 months (p < 0.001, 5.0% 36 months, 5.6% 48 6.1% 60 months). When restricting this panel without activity, 3.0% PIRMA 12 4.5% varying 5.3% 6.2% between RAW 15.6% and, absence further relapses, 9.7% 6.8% treatment. group associated significantly more frequently compared (20.7%; p 0.05), but a statistical difference later on. our work, confirmed that activity.

Язык: Английский

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Study protocol: randomised controlled trial evaluating exercise therapy as a supplemental treatment strategy in early multiple sclerosis: the Early Multiple Sclerosis Exercise Study (EMSES)

BMJ Open, Год журнала: 2021, Номер 11(1), С. e043699 - e043699

Опубликована: Янв. 1, 2021

In the relapsing remitting type of multiple sclerosis (MS) reducing relapses and neurodegeneration is crucial in halting long-term impact disease. Medical disease-modifying treatments have proven effective, especially when introduced early disease course. However, patients still experience activity disability progression, therefore, supplemental treatment strategies are warranted. Exercise appear to be one most promising strategies, but a somewhat overlooked 'window opportunity' exist The objective this study investigate exercise as supplementary strategy course MS.The presented Early Multiple Sclerosis Study 48-week (plus 1-year follow-up) national multicentre single-blinded parallel group randomised controlled trial comparing two groups receiving usual care plus supervised high-intense or health education (active control). Additionally, data will compared with population-based control only obtained from Danish MS Registry. primary outcomes annual relapse rate MRI derived global brain atrophy. secondary physical cognitive function, MS-related symptoms, exploratory outcomes. All analyses performed intention treat.The approved by Central Denmark Region Committees on Health Research Ethics (1-10-72-388-17) registered at Data Protection Agency (2016-051-000001 (706)). findings published scientific peer-reviewed journals relevant conferences.NCT03322761.

Язык: Английский

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Cost of illness in multiple sclerosis by disease characteristics – A review of reviews

Expert Review of Pharmacoeconomics & Outcomes Research, Год журнала: 2021, Номер 22(2), С. 177 - 195

Опубликована: Сен. 28, 2021

Introduction In light of the increasing number economic burden studies and heterogeneity in methodology reporting standards, there is a need for robust evidence synthesis on an umbrella review level.Areas covered We performed first reviews cost-of-illness multiple sclerosis. Focusing disaggregated costs by disease characteristics (disability level, relapse, course), we also characterized underlying methodological base individual (primary) studies.Expert Commentary identified 17 encompassing 111 unique primary studies, high degree overlap across reviews. Costs were substantial, rising with disability relapse episodes, progression. Disability was key cost driver. Compared to mild disability, total moderate 1.4–2.3-fold higher 1.8–2.9-fold severe disability. With escalating share outside health system (indirect costs, informal care) increasingly outweighed direct medical costs. Of all 72% gathered resource use/loss data patient self-report. Associated mostly reported level (75%), followed (48%) course (21%). conclusion, although can make in-depth comparisons impossible, important patterns are broadly apparent.

Язык: Английский

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Real-World Evidence on the Societal Economic Relapse Costs in Patients with Multiple Sclerosis

PharmacoEconomics, Год журнала: 2020, Номер 38(8), С. 883 - 892

Опубликована: Май 4, 2020

Relapses are the hallmark of multiple sclerosis (MS). Analyses have shown that cost MS increases during periods relapse. However, results inconsistent between studies, possibly due to different study designs and implications relapses with respect patient characteristics.The aims were estimate describe direct indirect relapse costs determine differences in characteristics. Furthermore, we pharmacoeconomic impact follow-up.Data extracted from two German, multicenter, observational studies applying a validated resource instrument. Relapse calculated as difference quarterly propensity score (PS)-matched patients without (1:1 ratio). For active patients, additionally prior determined post-relapse quarter.Of 1882 607 (32%) presented at least one After PS-matching, 597 inactive retained. (in 2019 values) ranged €791 (age 50 + years) €1910 (disease duration < 5 years). In mildly disabled recently diagnosed (range €1073-€1207) constantly outweighed €591-€703). The increase quarter was strongest for inpatient stays (+ 366%, €432; p 0.001), day admissions 228%, €57; absenteeism (127%, €463; 0.001). quarter, remained elevated relapse-associated worsening.A recent diagnosis mild disability lead high costs. suggest necessity incorporate characteristics when assessing

Язык: Английский

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