Publications by authors named "Marcin Mycko"
The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.
View Article and Find Full Text PDFCD4+ T cells are considered the main orchestrators of autoimmune diseases. Their disruptive effect on CD4+ T cell differentiation and the imbalance between T helper cell populations can be most accurately determined using experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). One epigenetic factor known to promote autoimmune inflammation is miRNA-155 (miR-155), which is significantly upregulated in inflammatory T cells.
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- Current disease-modifying therapies (DMTs) for multiple sclerosis (MS) often need to be taken for a long time, but aging and a weakened immune system (immunosenescence) raise concerns about their safety and effectiveness, especially in older patients.* -
- Studies suggest that adjusting DMTs, such as switching to lower-risk treatments or even stopping treatment entirely in older patients (55+), could maintain disease stability without significantly increasing risks.* -
- Research indicates that more extensive studies are needed to confirm the best approaches for DMT de-escalation in older MS patients to ensure patient safety while managing the disease effectively.*
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- X-linked adrenomyeloneuropathy (AMN) is a hereditary neurodegenerative disorder caused by ABCD1 gene mutations, leading to the buildup of very long-chain fatty acids (VLFCAs), with no effective treatment currently available.
- A small open-label study was conducted with three male patients aged 26-37 from a Polish hospital, who received three intrathecal infusions of mesenchymal stem cells (MSCs) derived from Wharton jelly, with assessments of muscle strength and walking speed over a 3-month period.
- The study found that all participants had significant improvements in lower limb muscle strength (increased by 25-43%) and showed a positive trend in walking speed, suggesting that
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- Environmental factors, particularly low vitamin D levels, are linked to the onset of multiple sclerosis (MS), which is characterized by inflammation and damage to the central nervous system.
- Vitamin D acts through its active form, 1α,25-dihydroxyvitamin D, by interacting with the vitamin D receptor to modulate gene expression and the immune response.
- The review explores how individual variations in response to vitamin D might influence MS susceptibility and considers vitamin D supplementation as a potential strategy for preventing or reducing MS-related autoimmunity.
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- Multiple sclerosis is a long-term brain and spinal cord disease that causes damage to nerve fibers, and while current treatments can slow progression, they don't cure it.
- Most patients respond positively to current therapies, but some experience rapid disease progression, and standard drug delivery methods often struggle to effectively target the central nervous system.
- Exploring alternative drug delivery methods that enhance drug accumulation in the brain could improve outcomes for those patients, potentially reducing side effects despite requiring more invasive methods.
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- Circular RNA (circRNA) is a new type of non-coding RNA that influences microRNA activity and is linked to the mechanisms of multiple sclerosis (MS).
- A study examined circRNA profiles in the blood of 20 patients with relapsing-remitting MS and 10 healthy controls, identifying 246 circRNAs that are significantly downregulated in MS patients.
- Validation of two specific circRNAs, hsa_circRNA_101145 and hsa_circRNA_001896, showed their levels decrease during MS remission, pointing to potential roles in critical pathways related to oxidative stress and blood-brain barrier function.
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- Multiple sclerosis (MS) is a complex disorder with varying symptoms and treatment responses, necessitating reliable biomarkers for diagnosis and prognosis.
- Traditional MS biomarkers have limited clinical value, prompting exploration of innovative options like neurofilament light chains (NfL), although their specificity poses challenges in clinical settings.
- Extracellular RNA, particularly microRNA (miRNA), and small extracellular vesicles are being investigated as potential new biomarkers for MS due to their roles in gene expression and communication in the central nervous system.
Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies.
View Article and Find Full Text PDFMultiple Sclerosis: circRNA Profile Defined Reveals Links to B-Cell Function.
Neurol Neuroimmunol Neuroinflamm
September 2021
Article Synopsis
- The study aimed to analyze the circular RNA (circRNA) profiles in patients with relapsing-remitting multiple sclerosis (RRMS) compared to healthy individuals, focusing on immune cells.
- Researchers utilized hybridization microarray technology to examine nearly 14,000 circRNAs in blood samples from 20 RRMS patients and 10 healthy controls, validating findings with a larger cohort.
- The results identified 914 circRNAs differentially expressed between RRMS patients and controls, with three specific circRNAs significantly elevated during disease relapse, suggesting potential roles in B-cell dysfunction and as biomarkers for monitoring RRMS activity.
B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic - when immunosuppression meets infection?
Neurol Neurochir Pol
January 2021
Article Synopsis
- Research shows that B cells play a crucial role in autoimmune demyelination and targeting them has become a key strategy in treating multiple sclerosis (MS), especially with new therapies introduced recently.
- The use of monoclonal antibodies like ocrelizumab has significantly improved disease management for relapsing-remitting and primary progressive MS patients, yet the COVID-19 pandemic has raised concerns about the safety of these treatments.
- Current evidence suggests that MS patients, including those undergoing B cell depletion therapies, do not face a higher risk of severe COVID-19, indicating that avoiding immune suppression may be more harmful than beneficial for managing their MS.
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- Th17 cells play a key role in autoimmune diseases like multiple sclerosis, but how they cause these conditions is not fully understood, necessitating research into their regulation by microRNAs (miRNA).
- Researchers created a T cell line mimicking Th17 characteristics and discovered that certain miRNAs are activated when Th17 cells are stimulated, and blocking these miRNAs decreased vital Th17 gene expressions.
- The study identified heat shock protein 70 (HSP70) as crucial for enabling miRNA function related to Th17, establishing a connection between cellular stress and autoimmune responses, suggesting potential therapeutic targets for treatment.
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- * In multiple sclerosis (MS), miRNA is linked to regulating immune responses and myelination, making it a promising target for treatments and disease markers.
- * Exosomes, tiny vesicles released by cells, are also important in immune signaling and inflammation, leading researchers to explore their potential in therapy and as biomarkers for MS.
Circular RNAs as a novel layer of regulatory mechanism in multiple sclerosis.
J Neuroimmunol
September 2019
Article Synopsis
- Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system, where immune cells mistakenly attack myelin, causing damage.
- Recent research highlights the role of epigenetics and specific microRNAs (miRNAs) in MS pathogenesis, with some miRNAs promoting inflammation while others aid in repair processes.
- Circular RNAs (circRNAs) can regulate miRNAs by acting as "sponges," potentially influencing MS progression and serving as stable biomarkers for the disease.
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- This study explores how exosomes, tiny vesicles that carry RNA, may play a role in the immune regulation of relapsing-remitting multiple sclerosis (RRMS) compared to healthy controls (HC).
- Researchers used next generation sequencing (NGS) to analyze the exosomal RNA profiles in 19 RRMS patients and 10 HC, identifying specific microRNAs (miRNAs) that were differentially expressed and significantly decreased during RRMS relapses.
- The findings suggest that the unique RNA profile in exosomes of RRMS patients could indicate disrupted communication between cells and that certain miRNAs might serve as potential biomarkers to differentiate between disease relapses.
Multiple sclerosis (MS) is a putative autoimmune disease of the central nervous system (CNS) in which autoreactive immune cells recognizing myelin antigens lead to demyelination and axonal injury. Mechanisms relevant to the pathogenesis of MS have not been fully elucidated, particularly those underlying initiation of immune system dysfunction. For example, it is not known how reactivity against CNS components is generated within the peripheral immune system.
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- Exosomes are small vesicles that aid in cell communication and immunity, and this study focuses on their role in multiple sclerosis (MS).
- The research analyzed serum samples from MS patients (both relapsing-remitting and secondary progressive) and healthy controls to detect myelin proteins in exosomes and measure their characteristics.
- Results showed that exosomes carried myelin proteins like MOG, which linked strongly to disease activity, suggesting that these exosomes could enhance immune responses against myelin in MS and may serve as new markers for monitoring the disease.
Unlabelled: microRNA-155 (miR-155) plays an important role in posttranscriptional gene regulation of the immune system. We and others have described miR-155 upregulation in T helper cells (Th) during the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We have shown that mice in which the miR-155 host gene (MIR155HG) has been deactivated are resistant to EAE.
View Article and Find Full Text PDFNotch receptors (Notch1-4) are involved in the differentiation of CD4 T cells and the development of autoimmunity. Mechanisms regulating Notch signaling in CD4 T cells are not fully elucidated. In this study we investigated potential crosstalk between Notch pathway molecules and heat shock protein 70 (Hsp70), the major intracellular chaperone involved in the protein transport during immune responses and other stress conditions.
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- MicroRNAs (miRNAs) play a key role in forming RNA-induced silencing complexes (RISCs) which regulate miRNA activity; however, their function in diseases like multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), remains unclear.
- Recent findings show that the levels of RISC proteins, specifically Ago2 and FXR1, are significantly dysregulated in various cell types during EAE, impacting oligodendrocytes and brain-infiltrating T cells.
- The altered RISC assembly leads to downregulation of miRNAs necessary for oligodendrocyte survival and myelin production, while promoting proinflammatory responses in T lymphocytes, suggesting a possible link
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- * In this study, researchers found that sulfatides significantly suppress T cell proliferation, especially in naive T helper cells, and this suppression is not related to cell death but rather to the induction of a state called anergy.
- * The study highlights sulfatides as key players in regulating T cell functions negatively and suggests their involvement in reducing susceptibility to autoimmune diseases, like multiple sclerosis, which shifts the focus from just myelin proteins to other brain-derived molecules.
Plasmacytoid dendritic cells (pDCs), an important immunoregulatory population, are characterized by vigorous secretion of type I interferons (IFNs) in response to toll-like receptor (TLR) 7 and 9 stimulation. We studied the function of pDCs in multiple sclerosis (MS) patients by analysis of TLR7 responses. We assessed a pDC secretion pattern of cytokines in the short term PBMC cultures stimulated with TLR7 agonist.
View Article and Find Full Text PDFMore than 80% of the human genome is biochemically active, whereas less than 3% of the genome encodes proteins. The emerging field of non-coding ribonucleic acids (RNAs) that are products of the genome, but do not program proteins, has revolutionized our understanding of cell biology. This was followed by a growing interest in the role of non-coding RNAs in the pathogenesis of human diseases, including multiple sclerosis (MS).
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