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Multiple Sclerosis: From Molecular Pathology to Novel Therapeutic Approaches

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 805

Special Issue Editors


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Guest Editor
1. HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary
2. Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
Interests: multiple sclerosis; neurodegeneration; smouldering lesion; molecular pathology; novel therapies; kynurenines
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos Krt. 113, H-6725 Szeged, Hungary
Interests: depression; anxiety; dementia pain; their comorbidities nature; translational research in neurological diseases; psychiatric disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple sclerosis (MS) is a chronic disease characterised by inflammation, extensive primary demyelination, and progressive neurodegenerative processes. Long-term disability in MS is largely independent of relapses (progression independent of relapse activity, PIRA) and correlates well with brain atrophy detected by MRI images. Smouldering lesions show a low-grade chronic inflammation characterised by chronic axonal damage and concurrent demyelination and are further characterised by a gradual increase in size towards the normal-appearing white matter (NAWM). During the course of the disease, the proportion of smouldering lesions increases over time and is higher in progressive than in relapsing–remitting disease. These lesions have also been shown to correlate with disability and predict progression in both relapsing–remitting and secondary progressive SM. It is important to revise the current disease classification system, clinical trial designs, and trial endpoints. Furthermore, novel molecular biomarkers (like NfL, GFAP, CHI3L, CXCL13, kynurenines, redox molecules, etc.) help the decision about the optimal treatment of MS patients.

Prof. Dr. László Vécsei
Dr. Masaru Tanaka
Guest Editors

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Keywords

  • progression-independent relapses (PIRAs)
  • smouldering-associated worsening (SAW)
  • lack of new relapses and of new magnetic resonance imaging activity (NEIDA)
  • slowly expanding lesions (SEL)
  • no evidence of smouldering disease activity (NESDA)
  • neurofilament (NfL)
  • glial fibrillary acidic protein (GFAP)
  • patient-reported outcome (PRO)
  • paramagnetic rim lesions (PRLs)
  • relapse-associated worsening (RAW)

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Published Papers (2 papers)

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Review

21 pages, 616 KiB  
Review
Biomarkers of Progression Independent of Relapse Activity—Can We Actually Measure It Yet?
by Gabriel Bsteh, Assunta Dal-Bianco, Nik Krajnc and Thomas Berger
Int. J. Mol. Sci. 2025, 26(10), 4704; https://doi.org/10.3390/ijms26104704 - 14 May 2025
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Abstract
Progression independent of relapse activity (PIRA) is increasingly recognized as a key driver of disability in multiple sclerosis (MS). However, the concept of PIRA remains elusive, with uncertainty surrounding its definition, underlying mechanisms, and methods of quantification. This review examines the current landscape [...] Read more.
Progression independent of relapse activity (PIRA) is increasingly recognized as a key driver of disability in multiple sclerosis (MS). However, the concept of PIRA remains elusive, with uncertainty surrounding its definition, underlying mechanisms, and methods of quantification. This review examines the current landscape of biomarkers used to predict and measure PIRA, focusing on clinical, imaging, and body fluid biomarkers. Clinical disability scores such as the Expanded Disability Status Scale (EDSS) are widely used, but may lack sensitivity in capturing subtle relapse-independent progression. Imaging biomarkers, including MRI-derived metrics (brain and spinal cord volume loss, chronic active lesions) and optical coherence tomography (OCT) parameters (retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning), offer valuable insights, but often reflect both inflammatory and neurodegenerative processes. Body fluid biomarkers, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), are promising indicators of axonal damage and glial activation, but their specificity for PIRA remains limited. This review emphasizes the distinction between predicting PIRA—identifying individuals at risk of future progression—and measuring ongoing PIRA-related disability in real time. We highlight the limitations of current biomarkers in differentiating PIRA from relapse-associated activity and call for a clearer conceptual framework to guide future research. Advancing the precision and utility of PIRA biomarkers will require multimodal approaches, longitudinal studies, and standardized protocols to enable their clinical integration and to improve personalized MS management. Full article
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17 pages, 1145 KiB  
Review
Exosomal microRNAs as Early Transition Biomarkers from Recurrent-Remissive to Secondary Progressive Multiple Sclerosis
by Oana Mosora, Smaranda Maier, Doina Manu, Laura Bărcuțean, Medeea Roman, Mihai Dumitreasă and Rodica Bălașa
Int. J. Mol. Sci. 2025, 26(8), 3889; https://doi.org/10.3390/ijms26083889 - 20 Apr 2025
Viewed by 285
Abstract
Multiple sclerosis (MS) is a chronic, immune-mediated disease that affects young adults, leading to neurological disability. Regardless of the studies and the research involved in developing an efficient disease-modifying therapy (DMT), relapsing-remitting multiple sclerosis (RRMS) will transition to a progressive multiple sclerosis phenotype. [...] Read more.
Multiple sclerosis (MS) is a chronic, immune-mediated disease that affects young adults, leading to neurological disability. Regardless of the studies and the research involved in developing an efficient disease-modifying therapy (DMT), relapsing-remitting multiple sclerosis (RRMS) will transition to a progressive multiple sclerosis phenotype. The moment of transition from RRMS to secondary progressive multiple sclerosis (SPMS) is difficult to predict, and the diagnosis is based on the accumulation of disabilities in the evolution of the disease. Research on microRNAs’ (miRNAs) role in MS began in the early 2000s, with miR-155 frequently cited for its link to blood–brain barrier dysfunction and neurodegeneration, making it an early transition biomarker from RRMS to SPMS. The purpose of this review is to reveal the importance of finding a biomarker from the molecular field that will be able to identify the transition phase so patients can receive high-efficacy treatments and to cease the clinical progression. Full article
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