scholarly journals Recent Advances in Antigen-Specific Immunotherapies for the Treatment of Multiple Sclerosis

2020 ◽  
Vol 10 (6) ◽  
pp. 333 ◽  
Author(s):  
Olga Kammona ◽  
Costas Kiparissides
Keyword(s):  
Multiple Sclerosis ◽  
Cell Receptor ◽  
Myelin Proteins ◽  
Dna Encoding ◽  
Disease Modifying Therapies ◽  
Tolerogenic Dendritic Cells ◽  
The Central Nervous System ◽  
Myelin Antigens ◽  
Shed Light

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy. This could be achieved via the development of immunotherapies designed to specifically suppress immune responses to self-antigens (e.g., myelin antigens). The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis (e.g., vaccination with myelin-derived peptides/proteins, plasmid DNA encoding myelin epitopes, tolerogenic dendritic cells pulsed with encephalitogenic epitopes of myelin proteins, attenuated autologous T cells specific for myelin antigens, T cell receptor peptides, carriers loaded/conjugated with myelin immunodominant peptides, etc.), focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis.

Multiple sclerosis: Serum-derived exosomes express myelin proteins

2017 ◽  
Vol 24 (4) ◽  
pp. 449-458 ◽  
Author(s):  
Grazyna Galazka ◽  
Marcin P Mycko ◽  
Igor Selmaj ◽  
Cedric S Raine ◽  
Krzysztof W Selmaj
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Cell Communication ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Myelin Proteins ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
The Central Nervous System ◽  
Serum Exosomes

Background: Exosomes are small extracellular vesicles that provide cell-to-cell communication and are involved in immunoregulation. Objective: To investigate serum exosomes for the presence of myelin proteins outside the central nervous system (CNS) and their role in multiple sclerosis (MS). Methods: Serum, cerebrospinal fluid (CSF), and peripheral blood mononuclear cell (PBMC) samples were collected from 45 patients with relapsing–remitting MS (RRMS), 30 patients with secondary progressive MS (SPMS), and 45 healthy controls. Exosomes were isolated using a polymer formulation method, and their size, concentration, and CNS myelin protein contents were measured by a nanoparticle tracking analysis, enzyme-linked immunosorbent assays, and Western blot. Results: We found that exosomes expressed three major myelin proteins, myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG). Exosomal content of MOG strongly correlated with disease activity and was highest in RRMS patients in relapse and in SPMS patients. Serum-derived exosomes induced proliferation of MOG-T cell receptor transgenic T cells confirming that serum exosomes maintained MOG immunogenicity. Conclusion: Exosomes isolated outside CNS tissue expressed myelin proteins, and the presence of MOG correlated strongly with disease activity. We conclude that exosomes might enhance and/or perpetuate anti-myelin immune reactions in MS and may provide novel markers of disease activity.

scholarly journals Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Therapeutic Benefit ◽  
Disease Modifying Therapies ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
Switch Group ◽  
Relevant Outcome

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

scholarly journals Efficacy of cognitive-behavioural psychotherapy in the treatment of chronic fatigue in patients with multiple sclerosis – a literature review

2021 ◽  
Vol 21 (1) ◽  
pp. 36-40
Author(s):  
Justyna Wiśniowska ◽  
◽  
Kamilla Puławska ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Chronic Fatigue ◽  
Research Groups ◽  
Long Term Effects ◽  
Short Term ◽  
Behavioural Model ◽  
Cognitive Behavioural ◽  
The Central Nervous System ◽  
Specific Factors

Fatigue is one of the most common symptoms seen in patients with multiple sclerosis. Cognitive-behavioural psychotherapy can be a non-pharmacological approach for these patients. Van Kessel and Moss-Morris developed a cognitive-behavioural model to explain multiple sclerosis-related fatigue (2006). According to this model, inflammatory and demyelinating factors present in the central nervous system trigger fatigue, while cognitive interpretation, anxiety, or depressive symptoms and resting lifestyle are maintaining factors. Based on the cognitive-behavioural model of fatigue in multiple sclerosis, a protocol encompassing 8 treatment sessions was developed. For over 10 years, studies have been conducted to verify the effectiveness of cognitive-behavioural psychotherapy in the treatment of fatigue in patients with multiple sclerosis. The so far obtained results show that cognitive-behavioural psychotherapy has a moderate short-term effect on reducing fatigue, while the effect size in the long-term is small. The obtained results were undoubtedly influenced by several factors: the heterogeneity of the procedures used, the size of the research groups, and the large number of disease-related intermediary variables. Further research should be conducted to identify specific factors responsible for the effectiveness of cognitive-behavioural psychotherapy in the treatment of fatigue and to assess the long-term effects of therapy.

scholarly journals Reliability in long-term clinical studies of disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review

PLoS ONE ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. e0231722 ◽  
Author(s):  
Rosa C. Lucchetta ◽  
Letícia P. Leonart ◽  
Marcus V. M. Gonçalves ◽  
Jefferson Becker ◽  
Roberto Pontarolo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Clinical Studies ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Therapeutic Apheresis in Acute Relapsing Multiple Sclerosis: Current Evidence and Unmet Needs—A Systematic Review

2019 ◽  
Vol 8 (10) ◽  
pp. 1623 ◽  
Author(s):  
Rolfes ◽  
Pfeuffer ◽  
Ruck ◽  
Melzer ◽  
Pawlitzki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Case Series ◽  
Current Evidence ◽  
Comparable Efficacy ◽  
Demyelinating Disorder ◽  
Published Evidence ◽  
The Central Nervous System ◽  
Technical Details ◽  
Relapsing Multiple Sclerosis

Multiple sclerosis (MS) is the most abundant inflammatory demyelinating disorder of the central nervous system. Despite recent advances in its long-term immunomodulatory treatment, MS patients still suffer from relapses, significantly contributing to disability accrual. In recent years, apheresis procedures such as therapeutic plasma exchange (TPE) and immunoadsorption (IA) have been recognized as two options for treating MS relapses, that do not respond to standard treatment with corticosteroids. TPE is already incorporated in most international guidelines, although evidence for its use resulted mostly from either case series or small unblinded and/or non-randomized trials. Data on IA are still sparse, but several studies indicate comparable efficacy between both apheresis procedures. This article gives an overview of the published evidence on TPE and IA in the treatment of acute relapses in MS. Further, we outline current evidence regarding individual outcome predictors, describe technical details of apheresis procedures, and discuss apheresis treatment in children and during pregnancy.

scholarly journals Identification of Monotonically Differentially Expressed Genes for IFN-β-Treated Multiple Sclerosis Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Suyan Tian ◽  
Lei Zhang
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Biologically Relevant ◽  
Therapeutic Mechanism ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Term Response

Multiple sclerosis (MS) is a common neurological disability of the central nervous system. Immune-modulatory therapy with interferon-β (IFN-β) has been used as a first-line treatment to prevent relapses in MS patients. While the therapeutic mechanism of IFN-β has not been fully elucidated, the data of microarray experiments that collected longitudinal gene expression profiles to evaluate the long-term response of IFN-β treatment have been analyzed using statistical methods that were incapable of dealing with such data. In this study, the GeneRank method was applied to generate weighted gene expression values and the monotonically expressed genes (MEGs) for both IFN-β treatment responders and nonresponders were identified. The proposed procedure identified 13 MEGs for the responders and 2 MEGs for the nonresponders, most of which are biologically relevant to MS. Our work here provides some useful insight into the mechanism of IFN-β treatment for MS patients. A full understanding of the therapeutic mechanism will enable a more personalized treatment strategy possible.

Natalizumab (Tysabri) in multiple sclerosis patients

2008 ◽  
Vol 9 (2) ◽  
pp. 109-114
Author(s):  
Viola Sacchi
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Symptom Relief ◽  
Interferon Β ◽  
Disease Modifying Therapies ◽  
Mental Symptoms ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Immunomodulating Drugs

Multiple sclerosis (MS) is an autoimmune disease where dysregulated immune system elements (i.e. leucocytes) react against different components of the central nervous system (CNS), in particular myelin structures, causing several physical and mental symptoms,often progressing to total disability. While some treatments for MS provide only symptom relief, the most commonly drugs administered for altering the course of the disease are DMTs (disease-modifying therapies); nevertheless for more than ten years the only DMTs available were interferon β, glatiramer acetate (two immunomodulating drugs) and mitoxantrone (an immunosuppressant).

Neuroprotective Therapies for Multiple Sclerosis

2012 ◽  
Vol 7 (3) ◽  
pp. 189 ◽  
Author(s):  
Beatriz Moreno ◽  
Pablo Villoslada ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Nervous System ◽  
Interferon Beta ◽  
Immunomodulatory Drugs ◽  
Neuroprotective Agents ◽  
Autoimmune Attack ◽  
The Central Nervous System ◽  
Genetic And Environmental Factors ◽  
Neuroprotective Therapies

Multiple sclerosis (MS) is considered to be an autoimmune disease that is caused by the immune system attacking the central nervous system (CNS) leading to myelin loss and axonal damage, resulting in long-term disability. The pathophysiology of MS is complex with involvement of genetic and environmental factors that define the susceptibility to generate the autoimmune attack. In the last decade, several immunomodulatory drugs have been approved, including recombinant proteins such as interferon-beta, monoclonal antibodies such as natalizumab, or small chemicals including glatiramer acetate. In addition, there is a wide pipeline of new immunomodulators finishing Phase II or III trials. However, at present there are no approved treatments that directly reduce nervous system damage or enhance its repair. Novel neuroprotective agents have been identified in pre-clinical studies but their development is being prevented by the absence of appropriate understanding of the mechanisms of CNS damage by inflammation as well as by the lack of clinical platforms to test them. In this review, we describe the different mechanisms of axonal injury and discuss some of the principal therapeutic candidates that could provide neuroprotection in MS.

scholarly journals Sphingosine-1-phosphate Receptor Modulators in Multiple Sclerosis

2018 ◽  
Vol 13 (1) ◽  
pp. 25 ◽  
Author(s):  
Patrick Vermersch
Keyword(s):  
Multiple Sclerosis ◽  
Oral Disease ◽  
Receptor Subtypes ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
S1p Receptor ◽  
Phase Ii And Iii ◽  
Receptor Modulators ◽  
Term Data

The introduction of oral disease modifying therapies has transformed the treatment landscape for patients with multiple sclerosis (MS). Fingolimod (Gilenya®, Novartis, Basel, Switzerland), the first oral therapy to be approved, has demonstrated clinical efficacy as a result of modulation of subtype 1 sphingosine-1-phosphate (S1P1) receptors. This leads to retention of lymphocytes in the lymph nodes, preventing their entry into the central nervous system. However, fingolimod can cause adverse effects as a result of its interaction with other S1P receptor subtypes, which are expressed in numerous tissues, including cardiac myocytes. More selective S1P receptor agents are currently in phase II and III clinical development. Siponimod, ozanimod, ponesimod and amiselimod have demonstrated efficacy with improved safety profiles compared with fingolimod. While more long-term data are needed, these selective S1P receptor modulators appear to be promising options for the treatment of MS and other disorders associated with autoimmunity and inflammation.

scholarly journals Current Advances in Pediatric Onset Multiple Sclerosis

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 71 ◽  
Author(s):  
Kristen S. Fisher ◽  
Fernando X. Cuascut ◽  
Victor M. Rivera ◽  
George J. Hutton
Keyword(s):  
Multiple Sclerosis ◽  
Current Knowledge ◽  
Pediatric Population ◽  
Treatment Patterns ◽  
Time Treatment ◽  
Disease Modifying Therapies ◽  
Autoimmune Inflammatory Disease ◽  
Significant Disability ◽  
The Central Nervous System ◽  
Over Time

Multiple sclerosis (MS) is an autoimmune inflammatory disease affecting the central nervous system leading to demyelination. MS in the pediatric population is rare, but has been shown to lead to significant disability over the duration of the disease. As we have learned more about pediatric MS, there has been a development of improved diagnostic criteria leading to earlier diagnosis, earlier initiation of disease-modifying therapies (DMT), and an increasing number of DMT used in the treatment of pediatric MS. Over time, treatment with DMT has trended towards the initiation of higher efficacy treatment at time of diagnosis to help prevent further disease progression and accrual of disability over time, and there is evidence in current literature that supports this change in treatment patterns. In this review, we discuss the current knowledge in diagnosis, treatment, and clinical outcomes in pediatric MS.

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