Exploring miRNAs’ Based Modeling Approach for Predicting PIRA in Multiple Sclerosis: A Comprehensive Analysis DOI Open Access

Tommaso Gosetti di Sturmeck,

Leonardo Malimpensa, Gina Ferrazzano

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6342 - 6342

Published: June 7, 2024

The current hypothesis on the pathophysiology of multiple sclerosis (MS) suggests involvement both inflammatory and neurodegenerative mechanisms. Disease Modifying Therapies (DMTs) effectively decrease relapse rates, thus reducing relapse-associated disability in people with MS. In some patients, progression, however, is not solely linked to new lesions clinical relapses but can manifest independently. Progression Independent Relapse Activity (PIRA) significantly contributes long-term disability, stressing urge unveil biomarkers forecast disease progression. Twenty-five adult patients relapsing–remitting (RRMS) were enrolled a cohort study, according latest McDonald criteria, tested before after high-efficacy (6–24 months). Through Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells. Multivariate logistic linear models interactions generated. Robustness was assessed by randomization tests R. A subset miRNAs, correlated PIRA, Expanded Disability Status Scale (EDSS), selected. To refine patient stratification connected trajectory, computed robust classification model derived baseline expression predict PIRA status (AUC = 0.971). We built an optimal multilinear selecting four other predictors describe EDSS changes compared baseline. modeling offers promising avenue uncover potential essential for accurate prediction progression early MS stages. These provide valuable insights into developing personalized effective treatment strategies.

Language: Английский

Topographical Mapping of Metabolic Abnormalities in Multiple Sclerosis using Rapid Echo-less 3D-MR Spectroscopic Imaging at 7T DOI Creative Commons
Eva Niess, Assunta Dal‐Bianco, Bernhard Strasser

et al.

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 121043 - 121043

Published: Jan. 1, 2025

Language: Английский

Citations

1
Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion DOI Creative Commons
Massimo Filippi, Maria Pia Amato, Carlo Avolio

et al.

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(2)

Published: Feb. 1, 2025

Language: Английский

Citations

1
Multifaceted Biomarkers Suggest a Similar Profile of CNS Pathology in Relapsing and Progressive MS DOI Creative Commons
Katelijn M. Blok, Romy A. M. Klein Kranenbarg,

Kirtana Ananth

et al.

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(2)

Published: Feb. 1, 2025

ABSTRACT Background Relapsing–remitting (RR) and primary progressive (PP) multiple sclerosis (MS) have distinct clinical courses, but underlying pathophysiological differences remain unclear. We compared pathological components between RRMS, PPMS, other inflammatory neurodegenerative disorders, leveraging soluble biomarkers post‐mortem pathology. Methods Serum cerebrospinal fluid (CSF) of people diagnosed with (pw) PPMS ( n = 104), RRMS 38), Alzheimer's disease (AD, 22), neuromyelitis optica spectrum disorder (NMOSD, 10), myelin oligodendrocyte glycoprotein–associated (MOGAD, 10) were collected. B‐cell maturation antigen (BCMA), CD27 (sCD27), osteopontin (OPN), chitinase‐3‐like‐1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) synaptosomal‐associated protein‐25 (SNAP25) measured. Lymphocytes (CD20 + , CD138 CD3 ) pyramidal‐tract axonal density in RR‐onset 86) 45) brain tissue quantified. Results Soluble did not differ pwRRMS pwPPMS. Compared to AD, MS had higher CSF sCD27 p < 0.001) lower serum CHI3L1 GFAP, OPN SNAP25 (all 0.05). was than NMOSD 0.013). Principal component analyses K‐means clustering showed substantial overlap biomarkers, from AD. In all pwMS, NfL BCMA correlated clinical/radiological activity, parameters, Expanded Disability Status Scale (EDSS) score. Conclusions biomarker profiles pathology do differentiate diagnoses reflect the extent inflammation damage. Detailed assessment MS‐associated damage may enhance classification therapeutic strategies.

Language: Английский

Citations

1
The contribution of tumor necrosis factor to multiple sclerosis: a possible role in progression independent of relapse? DOI Creative Commons
Valentina Mazziotti, Francesco Crescenzo, Ermanna Turano

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 21, 2024

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Specifically, it has been recognized as an essential pro-inflammatory implicated in multiple sclerosis (MS) pathogenesis progression. MS chronic disease of the central nervous system, characterized by multifocal acute inflammatory demyelination white grey matter, along with neuroaxonal loss. A recent concept field research disability resulting from Progression Independent Relapse Activity (PIRA). PIRA recognizes that accumulation since early phase can occur independently relapse activity overcoming traditional dualistic view either relapsing-inflammatory or progressive-neurodegenerative disease. Several studies have demonstrated upregulation TNF expression both active brain lesions. Additionally, elevated levels observed serum cerebrospinal fluid patients. appears to play significant role maintaining intrathecal inflammation, promoting axonal damage neurodegeneration, consequently contributing progression accumulation. In summary, this review highlights current understanding its receptors progression, specifically focusing on relatively unexplored condition. Further area holds promise for potential therapeutic interventions targeting mitigate

Language: Английский

Citations

5
The Compelling Role of Brain‐Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, acting as signal and neuromodulator in the central nervous system (CNS). BDNF synthesized from its precursor proBDNF within CNS peripheral tissues. Through activation of NTRK2/TRKB (neurotrophic receptor tyrosine kinase 2), promotes neuronal survival, synaptic plasticity, growth, whereas it inhibits microglial release pro-inflammatory cytokines. dysregulated different neurodegenerative diseases depressions. However, there major controversy concerning levels stages multiple sclerosis (MS). Therefore, this review discusses potential role signaling MS, how modulators affect pathogenesis outcomes disease.

Language: Английский

Citations

4
A Window into New Insights on Progression Independent of Relapse Activity in Multiple Sclerosis: Role of Therapies and Current Perspective DOI Open Access
Tommaso Guerra, Pietro Iaffaldano

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 884 - 884

Published: Jan. 21, 2025

In multiple sclerosis (MS), there is significant evidence indicating that both progression independent of relapse activity (PIRA) and relapse-related worsening events contribute to the accumulation progressive disability from onset disease throughout its course. Understanding compartmentalized pathophysiology MS would enhance comprehension mechanisms, overcoming traditional distinction in phenotypes. Smoldering thought be maintained by a continuous interaction between parenchymal chronic processes neuroinflammation neurodegeneration intrathecal compartment. This review provides comprehensive up-to-date overview neuropathological immunological related mechanisms underlying PIRA phenomena MS, with focus on studies investigating impact currently available therapies these complex mechanisms.

Language: Английский

Citations

0
MicroRNA signatures of CD4+ T cell subsets in healthy and multiple sclerosis subjects determined by small RNA-sequencing DOI Creative Commons
Slobodan Čulina, Pierre‐Henri Commère, Élodie Turc

et al.

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: 401, P. 578531 - 578531

Published: Feb. 1, 2025

Language: Английский

Citations

0
Ethnoracial disparities in gray matter atrophy are mediated by structural disconnectivity in multiple sclerosis DOI Creative Commons
Ahmed Bayoumi,

Joseph Thomas,

Breanna Alonzo

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Objective To investigate ethnoracial disparities in gray matter (GM) atrophy, the contribution of white lesions and consequent structural disconnectivity among patients with multiple sclerosis (MS). Methods This retrospective study included 297 MS (pwMS), 98 Hispanic/Latinx (H‐MS), 82 non‐Hispanic Black (B‐MS), 117 White (W‐MS). GM atrophy was assessed using univariate, voxel‐based morphometry, multivariate techniques, source‐based morphometry. Structural secondary to evaluated network modification tool. Mediation analyses explored relationships between groups, lesions, disconnectivity, atrophy. Results B‐MS H‐MS generally exhibited greater compared W‐MS, particularly temporal, parahippocampal, precuneus, cuneus GM. differences were most prominent hippocampal, cingulate, deep regions. revealed that lesion load significantly mediated group global (percent = 52.4%), while some specific components, notably matter, insular, anterior cingulate Interpretation Significant exist its patterns diverse patients, partially by disconnectivity. These findings underscore importance considering factors research clinical practice, potentially informing personalized treatment strategies emphasizing need for representation trials.

Language: Английский

Citations

0
Cognitive Progression Independent of Relapse and MRI Activity in Multiple Sclerosis DOI
Stefano Ziccardi, Tom Fuchs, Maddalena Guandalini

et al.

Published: Feb. 19, 2025

Language: Английский

Citations

0
Monitoring multiple sclerosis: digital and fluid phase biomarkers DOI

Kayla Ward,

Stephen Reddel, Letizia Leocani

et al.

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Purpose of review Monitoring disease activity and treatment response in multiple sclerosis (MS) currently relies on the integration qualitative clinical radiological data that is limited predictive value. An array quantitative digital fluid biomarkers, many cusp broad translation, expected to herald a new era data-driven therapeutic strategy, particularly with respect sequencing disease-modifying therapies (DMTs). Available highly-effective DMTs, which largely abolish acute inflammatory early, relapsing MS, have impact progressive MS biology. However, robust biomarkers progression independent relapse (PIRA) emerged as major unmet need, fuelled by imminent availability treatments target pathomechanisms such chronic active or smouldering brain inflammation. Recent findings The criteria for diagnosis incorporate both imaging cerebrospinal (CSF) disease, lacks single diagnostic ‘test’. recent validation objective CSF k-FLC index, promises improve accuracy, patients atypical minor changes. Precision monitoring therapy being transformed advent clinically integrated, tools; wearables patient reported outcomes, including cognitive batteries delivered personal devices; an ultra-sensitive, readily-obtained serum indicate severity tissue injury MS. promise strategy further explored multimodal digital/fluid twin biomarker studies artificial intelligence algorithms. Summary Here, we key near-term will guide individualised people targeting no evidence (NEDA) early established disease. In medium term, composite integrated outcomes underpinned transformative effect management

Language: Английский

Citations

0