Advances in Multiple Sclerosis Research–Series I

Apostolopoulos, Vasso; Matsoukas, John

doi:10.3390/brainsci10110795

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Despite the substantial advances in the understanding of MS pathology, none of the currently existing therapies are able to stop the course of the disease by inducing a long-term remission [ 18 , 29 , 30 ]. Nowadays, available treatments are based on a continuous dependence on nonspecific immunosuppressive or immunomodulatory drugs [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], exposing patients to potentially serious adverse effects, that may compromise their safety and adherence to therapy [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Therapy of Vitamin D3-Tolerogenic Dendritic Cells and Interferon-β in a Preclinical Model of Multiple Sclerosis

et al. 2021

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Autologous antigen-specific therapies based on tolerogenic dendritic cells (tolDC) offer the possibility to treat autoimmune diseases by restoring homeostasis and targeting specifically autoreactive responses. Here, we explore the hypothesis that systemic inflammation occurring in autoimmune diseases, such as multiple sclerosis (MS), can generate a disease-specific environment able to alter the functionality of tolDC. In this context in fact, a combined therapy of tolDC with an immunomodulatory treatment could potentiate the beneficial effect of this antigen-specific cell therapy. For this purpose, we analyzed the efficacy of a combined therapy based on the use of vitamin D3 (VitD3)-tolDC plus interferon beta (IFN-beta) in MS. VitD3-tolDC were generated from healthy donors and MS patients and co-cultured with allogeneic peripheral blood mononuclear cells, in the presence or absence of IFN-beta. In vitro, VitD3-tolDC treatment reduced the percentage of activated T cells and allogeneic proliferation, whereas VitD3-tolDC+IFN-beta treatment enhanced the suppressive ability of VitD3-tolDC and, additionally, induced a shift towards a Th2 profile. To determine the clinical benefit of the combined therapy, C57BL/6-experimental autoimmune encephalomyelitis (EAE)-induced mice were treated with antigen-specific VitD3-tolDC and/or IFN-beta. Treatment of EAE mice with combined therapy ameliorated the disease course compared to each monotherapy. These results suggest that a combined therapy based on antigen-specific VitD3-tolDC and IFN-beta may represent a promising strategy for MS patients.

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Section: Discussionmentioning

confidence: 99%

Combined Therapy of Vitamin D3-Tolerogenic Dendritic Cells and Interferon-β in a Preclinical Model of Multiple Sclerosis

et al. 2021

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“…Multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, is characterized by the demyelination of neurons, gliosis, and various degrees of axonal and oligodendrocyte pathology. It is an immune-mediated disease influenced by both genetic and environmental factors [ 94 ]. It causes a wide array of neurological deficits, such as loss of vision, numbness, fatigue, and cognitive and motor impairment that vary depending on the location of the lesion [ 95 ].…”

Section: Effects Of Lps On Models Of Major Neurodegenerative Diseasesmentioning

confidence: 99%

Role of Endogenous Lipopolysaccharides in Neurological Disorders

Kalyan

Tousif

Sonali

et al. 2022

Cells

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Lipopolysaccharide (LPS) is a cell-wall immunostimulatory endotoxin component of Gram-negative bacteria. A growing body of evidence reveals that alterations in the bacterial composition of the intestinal microbiota (gut dysbiosis) disrupt host immune homeostasis and the intestinal barrier function. Microbial dysbiosis leads to a proinflammatory milieu and systemic endotoxemia, which contribute to the development of neurodegenerative diseases and metabolic disorders. Two important pathophysiological hallmarks of neurodegenerative diseases (NDDs) are oxidative/nitrative stress and inflammation, which can be initiated by elevated intestinal permeability, with increased abundance of pathobionts. These changes lead to excessive release of LPS and other bacterial products into blood, which in turn induce chronic systemic inflammation, which damages the blood–brain barrier (BBB). An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis. Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment. LPS-induced inflammation causes inappropriate activation of microglia, astrocytes, and dendritic cells. Consequently, these alterations negatively affect mitochondrial function and lead to increases in oxidative/nitrative stress and neuronal senescence. These cellular changes in the brain give rise to specific clinical symptoms, such as impairment of locomotor function, muscle weakness, paralysis, learning deficits, and dementia. This review summarizes the contributing role of LPS in the development of neuroinflammation and neuronal cell death in various neurodegenerative diseases.

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“…Multiple sclerosis (MS) is an inflammatory autoimmune-mediated disorder of the central nervous system involving a complex immune activation response, including T cells, B cells, and pro-inflammatory cytokines which attack the myelin sheath [1][2][3][4][5][6][7]. As such, there is demyelination of neurons resulting in axonal loss, neuronal functionality, and disability [8].…”

Section: Introductionmentioning

confidence: 99%

“…As proteins are large complex structures, often having numerous lysine residues, conjugation completion is often achieved; however, short peptides often do not contain multiple lysines, and conjugation efficacy is limited. As such, a small lysine linker comprising five lysine-glycine amino acids (Lys-Gly) 5 or (KG) 5 [5,19] has been developed, enabling effective conjugation between mannan and peptides. In these studies, a method for estimating the complete conjugation of peptide to mannan and its stability over time is crucial for translating this platform into human clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Myelin Peptide–Mannan Conjugate Multiple Sclerosis Vaccines: Conjugation Efficacy and Stability of Vaccine Ingredient

Matsoukas

Deraos²,

Kelaidonis³

et al. 2021

Vaccines

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Myelin peptide–mannan conjugates have been shown to be potential vaccines in the immunotherapy of multiple sclerosis. The conjugates are comprised from the epitope peptide and the polysaccharide mannan which transfers as a carrier the antigenic peptide to dendritic cells that process and present antigenic peptides at their surface in complex with MHC class I or class II resulting in T-cell stimulation. The conjugation of antigenic peptide with mannan occurs through the linker (Lys–Gly)5, which connects the peptide with the oxidized mannose units of mannan. This study describes novel methods for the quantification of the vaccine ingredient peptide within the conjugate, a prerequisite for approval of clinical trials in the pursuit of multiple sclerosis therapeutics. Myelin peptides, such as MOG35–55, MBP83–99, and PLP131–145 in linear or cyclic form, as altered peptide ligands or conjugated to appropriate carriers, possess immunomodulatory properties in experimental models and are potential candidates for clinical trials.

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Advances in Multiple Sclerosis Research–Series I

Cited by 6 publications

References 35 publications

Combined Therapy of Vitamin D3-Tolerogenic Dendritic Cells and Interferon-β in a Preclinical Model of Multiple Sclerosis

Combined Therapy of Vitamin D3-Tolerogenic Dendritic Cells and Interferon-β in a Preclinical Model of Multiple Sclerosis

Role of Endogenous Lipopolysaccharides in Neurological Disorders

Myelin Peptide–Mannan Conjugate Multiple Sclerosis Vaccines: Conjugation Efficacy and Stability of Vaccine Ingredient

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