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Biomolecules
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The Molecular Mechanisms and Therapeutics in Multiple Sclerosis
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The Molecular Mechanisms and Therapeutics in Multiple Sclerosis

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 19190

Special Issue Editors

Prof. Dr. Paulus Stefan Rommer

E-Mail Website
Guest Editor
Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria
Interests: multiple sclerosis; NMOSD; autoimmune encephalitis; biomarkers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Uwe Klaus Zettl

E-Mail Website
Guest Editor
Department of Neurology, Neuroimmunological Section, University of Rostock, 18147 Rostock, Germany
Interests: neuroimmunology; multiple sclerosis; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple sclerosis is a neuroinflammatory and neurodegenerative disease and the leading cause of neurological disability in young adults. More than 2 million patients are affected worldwide. In the last two decades, there has been unimaginable progress in treatment. While treatment options for relapsing MS are already well established, treatment options for progressive MS remain limited. The ultimate goal of curing MS has still not been achieved and will not be achievable for the foreseeable future.

The aim of this thematic collection of Biomolecules is to highlight recent findings in pathophysiology, histopathology, and their translation into therapeutic concepts. We encourage contributions on the latest immunological and pathophysiological findings, latest therapeutic concepts with special focus on progressive courses, and future therapeutic options. Studies dealing with biomarkers, in diagnostic and prognostic but also therapeutic areas, are also of particular interest.

Prof. Dr. Paulus Stefan Rommer
Prof. Dr. Uwe Klaus Zettl
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Histopathology in MS
  • innate and adaptive immunity
  • autoimmunity
  • relapsing and progressive MS
  • Treatment options in MS
  • Biomarkers in MS

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Published Papers (4 papers)

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Research

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14 pages, 970 KiB  
Article
Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis
by Margarete M. Voortman, Anna Damulina, Lukas Pirpamer, Daniela Pinter, Alexander Pichler, Christian Enzinger, Stefan Ropele, Gerhard Bachmaier, Juan-Jose Archelos, Gunther Marsche and Michael Khalil
Biomolecules 2021, 11(9), 1264; https://doi.org/10.3390/biom11091264 - 25 Aug 2021
Cited by 5 | Viewed by 2826
Abstract
Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal [...] Read more.
Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS. Full article
(This article belongs to the Special Issue The Molecular Mechanisms and Therapeutics in Multiple Sclerosis)
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Review

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30 pages, 1439 KiB  
Review
Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis
by Michael Hecker, Jan Bühring, Brit Fitzner, Paulus Stefan Rommer and Uwe Klaus Zettl
Biomolecules 2021, 11(10), 1510; https://doi.org/10.3390/biom11101510 - 13 Oct 2021
Cited by 27 | Viewed by 7550
Abstract
Telomeres are protective structures at the ends of linear chromosomes. Shortened telomere lengths (TL) are an indicator of premature biological aging and have been associated with a wide spectrum of disorders, including multiple sclerosis (MS). MS is a chronic inflammatory, demyelinating and neurodegenerative [...] Read more.
Telomeres are protective structures at the ends of linear chromosomes. Shortened telomere lengths (TL) are an indicator of premature biological aging and have been associated with a wide spectrum of disorders, including multiple sclerosis (MS). MS is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system. The exact cause of MS is still unclear. Here, we provide an overview of genetic, environmental and lifestyle factors that have been described to influence TL and to contribute to susceptibility to MS and possibly disease severity. We show that several early-life factors are linked to both reduced TL and higher risk of MS, e.g., adolescent obesity, lack of physical activity, smoking and vitamin D deficiency. This suggests that the mechanisms underlying the disease are connected to cellular aging and senescence promoted by increased inflammation and oxidative stress. Additional prospective research is needed to clearly define the extent to which lifestyle changes can slow down disease progression and prevent accelerated telomere loss in individual patients. It is also important to further elucidate the interactions between shared determinants of TL and MS. In future, cell type-specific studies and advanced TL measurement methods could help to better understand how telomeres may be causally involved in disease processes and to uncover novel opportunities for improved biomarkers and therapeutic interventions in MS. Full article
(This article belongs to the Special Issue The Molecular Mechanisms and Therapeutics in Multiple Sclerosis)
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15 pages, 1618 KiB  
Review
The Immunological Therapeutic Strategies for Controlling Multiple Sclerosis: Considerations during the COVID-19 Pandemic
by Maryam Azimzadeh, Nora Möhn, Sajjad Ghane Ezabadi, Zahra Moghimi Esfandabadi, Alireza Soleimani, Elaheh Ranjbar, Maliheh Jahromi, Reihaneh Seyedebrahimi, Thomas Skripuletz and Farshad Moharrami Kasmaie
Biomolecules 2021, 11(9), 1372; https://doi.org/10.3390/biom11091372 - 17 Sep 2021
Cited by 4 | Viewed by 4048
Abstract
A growing body of evidence initially suggested that patients with multiple sclerosis (MS) might be more susceptible to coronavirus disease 2019 (COVID-19). Moreover, it was speculated that patients with MS treated with immunosuppressive drugs might be at risk to develop a severe diseases [...] Read more.
A growing body of evidence initially suggested that patients with multiple sclerosis (MS) might be more susceptible to coronavirus disease 2019 (COVID-19). Moreover, it was speculated that patients with MS treated with immunosuppressive drugs might be at risk to develop a severe diseases course after infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2). However, the recently published data have shown that MS patients do not have a higher risk for severe COVID-19. Although there is no indication that patients with MS and immunomodulatory/immunosuppressive therapy are generally at a higher risk of severe COVID-19, it is currently being emphasized that the hazards of poorly treated MS may outweigh the putative COVID-19 dangers. In this review, we discuss the challenges and considerations for MS patients in the COVID-19 pandemic. Full article
(This article belongs to the Special Issue The Molecular Mechanisms and Therapeutics in Multiple Sclerosis)
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23 pages, 920 KiB  
Review
Measuring Treatment Response in Progressive Multiple Sclerosis—Considerations for Adapting to an Era of Multiple Treatment Options
by Nik Krajnc, Thomas Berger and Gabriel Bsteh
Biomolecules 2021, 11(9), 1342; https://doi.org/10.3390/biom11091342 - 10 Sep 2021
Cited by 6 | Viewed by 3471
Abstract
Disability in multiple sclerosis accrues predominantly in the progressive forms of the disease. While disease-modifying treatment of relapsing MS has drastically evolved over the last quarter-century, the development of efficient drugs for preventing or at least delaying disability in progressive MS has proven [...] Read more.
Disability in multiple sclerosis accrues predominantly in the progressive forms of the disease. While disease-modifying treatment of relapsing MS has drastically evolved over the last quarter-century, the development of efficient drugs for preventing or at least delaying disability in progressive MS has proven more challenging. In that way, many drugs (especially disease-modifying treatments) have been researched in the aspect of delaying disability progression in patients with a progressive course of the disease. While there are some disease-modifying treatments approved for progressive multiple sclerosis, their effect is moderate and limited mostly to patients with clinical and/or radiological signs of disease activity. Several phase III trials have used different primary outcomes with different time frames to define disease progression and to evaluate the efficacy of a disease-modifying treatment. The lack of sufficiently sensitive outcome measures could be a possible explanation for the negative clinical trials in progressive multiple sclerosis. On the other hand, even with a potential outcome measure that would be sensitive enough to determine disease progression and, thus, the efficacy or failure of a disease-modifying treatment, the question of clinical relevance remains unanswered. In this systematic review, we analyzed outcome measures and definitions of disease progression in phase III clinical trials in primary and secondary progressive multiple sclerosis. We discuss advantages and disadvantages of clinical and paraclinical outcome measures aiming for practical ways of combining them to detect disability progression more sensitively both in future clinical trials and current clinical routine. Full article
(This article belongs to the Special Issue The Molecular Mechanisms and Therapeutics in Multiple Sclerosis)
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