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Article ; Online: Recent advances and remaining questions of autologous hematopoietic stem cell transplantation in multiple sclerosis.

Bose, Gauruv / Freedman, Mark S

2021 Volume 421, Page(s) 117324

Abstract: The judicious use of autologous hematopoietic stem cell transplantation (AHSCT) for MS requires understanding the potential benefits, identifying the most appropriate patient, and acknowledging the risks and differences between different protocols. ... ...

Abstract	The judicious use of autologous hematopoietic stem cell transplantation (AHSCT) for MS requires understanding the potential benefits, identifying the most appropriate patient, and acknowledging the risks and differences between different protocols. Recently, AHSCT for MS is occurring more frequently, with a better safety profile than earlier studies. This review assesses recently published studies to determine the advances that have been made and remaining questions that future studies are poised to answer. We included studies from January 2016 to November 2020 with 20 or more patients. The benefits of AHSCT, including "no evidence of disease activity", functional and patient-reported outcomes, novel biomarkers such as brain atrophy or neurofilament light chain, and cost-effectiveness were assessed. The patient selection, treatment protocols, and safety outcomes differ between reports. The overall efficacy of AHSCT is better than standard treatments. Younger patients with highly active disease have greater chance for improvement, while patients who have comorbidities, failed more treatments, and are transitioning to a more progressive phase may not respond as well to AHSCT. The safety profiles for all AHSCT protocols is improving, however the durability of treatment response may not be the same for all protocols. The goal of AHSCT is to stop disease activity, avoid worsening disability, and obviate the need for further disease-modifying treatment, while improving patient quality of life and minimizing treatment-related risk. Results from currently enrolling randomized controlled trials, as well as ongoing registries, will provide more evidence for the safe and appropriate use of AHSCT.
MeSH term(s)	Cost-Benefit Analysis ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Sclerosis/therapy ; Quality of Life ; Transplantation, Autologous
Language	English
Publishing date	2021-01-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2021.117324
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Article ; Online: Reactivation of SARS-CoV-2 after Rituximab in a Patient with Multiple Sclerosis.

Bose, Gauruv / Galetta, Kristin

Multiple sclerosis and related disorders

2021 Volume 52, Page(s) 102922

Abstract: A 32-year-old woman with highly active MS was infected with SARS-CoV-2 while on treatment with rituximab. She recovered and was symptom-free for 21 days before receiving rituximab and IVIg for comorbid hypogammaglobulinemia. Three days after the infusion ...

Abstract	A 32-year-old woman with highly active MS was infected with SARS-CoV-2 while on treatment with rituximab. She recovered and was symptom-free for 21 days before receiving rituximab and IVIg for comorbid hypogammaglobulinemia. Three days after the infusion she redeveloped respiratory symptoms and required admission. Three SARS-CoV-2 nasopharyngeal swabs and antibody testing was negative; however, bronchial alveolar lavage detected SARS-CoV-2. Reactivation of SARS-CoV-2 after rituximab for MS has not been reported but is a known risk in other conditions. The timing of anti-CD20 treatment after SARS-CoV-2 infection requires further investigation and individual consideration to reduce the risk of reactivation.
MeSH term(s)	Adult ; Antigens, CD20 ; COVID-19 ; Female ; Humans ; Multiple Sclerosis ; Rituximab ; SARS-CoV-2
Chemical Substances	Antigens, CD20 ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2021-03-25
Publishing country	Netherlands
Document type	Case Reports ; Letter
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2021.102922
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Article: Autoimmune diseases and cancers overlapping with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A systematic review.

Molazadeh, Negar / Bose, Gauruv / Lotan, Itay / Levy, Michael

Multiple sclerosis journal - experimental, translational and clinical

2022 Volume 8, Issue 4, Page(s) 20552173221128170

Abstract: Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has various similarities with AQP4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG + NMOSD) in terms of clinical presentations, magnetic resonance ... ...

Abstract	Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has various similarities with AQP4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG + NMOSD) in terms of clinical presentations, magnetic resonance imaging (MRI) findings, and response to treatment. But unlike AQP4-IgG + NMOSD, which is known to coexist with various autoimmune diseases and cancers, an association of MOGAD with these conditions is less clear. Methods: We conducted a systematic search in PubMed, Scopus, Web of Science, and Embase based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Duplicates were removed using Mendeley 1.19.8 (USA production) and the citations were uploaded into Covidence systematic review platform for screening. Results: The most common autoimmune disease overlapping with MOGAD was anti-N-Methyl-D-Aspartate receptor encephalitis (anti-NMDAR-EN), followed by autoimmune thyroid disorders, and the most common autoantibody was antinuclear antibody (ANA), followed by AQP4-IgG (double-positive MOG-IgG and AQP4-IgG). A few sporadic cases of cancers and MOG-IgG-associated paraneoplastic encephalomyelitis were found. Conclusion: Unlike AQP4-IgG + NMOSD, MOGAD lacks clustering of autoimmune diseases and autoantibodies associated with systemic and organ-specific autoimmunity. Other than anti-NMDAR-EN and perhaps AQP4-IgG + NMOSD, the evidence thus far does not support the need for routine screening of overlapping autoimmunity and neoplasms in patients with MOGAD.
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2841884-0
ISSN	2055-2173 ; 2055-2173
ISSN (online)	2055-2173
ISSN	2055-2173
DOI	10.1177/20552173221128170
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Article ; Online: Anti-CGRP therapies for migraine in multiple sclerosis patients.

Gonzalez-Martinez, Alicia / Bose, Gauruv / Chitnis, Tanuja

Multiple sclerosis (Houndmills, Basingstoke, England)

2022 Volume 28, Issue 13, Page(s) 2149–2150

MeSH term(s)	Antibodies, Monoclonal ; Humans ; Migraine Disorders/drug therapy ; Multiple Sclerosis/complications ; Multiple Sclerosis/drug therapy
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2022-05-14
Publishing country	England
Document type	Letter ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/13524585221096353
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Article ; Online: Precision medicine in the multiple sclerosis clinic: Selecting the right patient for the right treatment.

Bose, Gauruv / Freedman, Mark S

Multiple sclerosis (Houndmills, Basingstoke, England)

2020 Volume 26, Issue 5, Page(s) 540–547

Abstract: Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system (CNS), affecting patients of all ages, causing neurologic disability if inadequately treated. Some patients have a relatively benign disease course without ... ...

Abstract	Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system (CNS), affecting patients of all ages, causing neurologic disability if inadequately treated. Some patients have a relatively benign disease course without significant disability after decades, while a more aggressive course ensues in others and disability progression occurs after only several years. Certain risk factors confer a higher chance of a patient having aggressive MS. Currently over 15 disease-modifying treatments (DMTs) are approved for MS with different efficacy and safety profiles. Deciding which DMT to use in a specific patient requires a careful analysis of a patient's disease course for high-risk factors for early progression, consideration of the efficacy and safety profile for potential therapy, as well as understanding of a patient's lifestyle and expectations. The integration of these factors is the art of precision medicine, a necessary practice in the treatment of patients with MS.
MeSH term(s)	Humans ; Immunologic Factors/administration & dosage ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/drug therapy ; Patient-Centered Care/methods ; Patient-Centered Care/standards ; Precision Medicine/methods ; Precision Medicine/standards
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2020-01-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458519887324
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Article ; Online: Progression independent of relapses in aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and multiple sclerosis.

Molazadeh, Negar / Akaishi, Tetsuya / Bose, Gauruv / Nishiyama, Shuhei / Chitnis, Tanuja / Levy, Michael

Multiple sclerosis and related disorders

2023 Volume 80, Page(s) 105093

Abstract: Objectives: To determine whether progression independent of relapse activity (PIRA) is present in Aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) ... ...

Abstract	Objectives: To determine whether progression independent of relapse activity (PIRA) is present in Aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and relapsing remitting Multiple sclerosis (RRMS). Methods: We retrospectively studied the change in EDSS, confirmed disability worsening (CDW) (i.e., PIRA), and new MRI lesions in AQP4+NMOSD, and MOGAD and MS patients. Linear mixed-effect regression model was used to compare the longitudinal changes in EDSS, and Cox regression was used to compare changes in MRI. Results: The estimated mean ΔEDSS in the AQP4+NMOSD and matched MS group were +0.06 (95%CI: -0.40, +0.52, p = 0.76), and +0.02 (95%CI: -0.05, +0.08, p = 0.6) respectively. The same estimate was -0.08 (95%CI: -0.18, +0.02, p = 0.12) in MOGAD and +0.05 (95%CI: -0.05, +0.15, p = 0.35) in matched MS group. Comparing groups for the presence of CDW (i.e., PIRA) showed that PIRA is more associated with MS compared to AQP4+NMOSD (p = 0.02) and MOGAD (p<0.001). Compared to their matched MS groups, the annualized rate of PIRA was significantly lower in AQP4 (0.08 vs 0.44; p<0.0001), and MOG groups (0.04 vs 0.13; p<0.0001). New T2 or enhancing lesions on brain MRI were higher in MS compared to AQP4+NMOSD and MOGAD patients. Conclusion: Relapse-independent changes in the EDSS, CDW, and MRI activity are not common in AQP4+NMOSD and MOGAD, especially when compared with MS. Since our patients were on relapse prevention therapies at the time of EDSS measurements, our study supports the importance of preventing relapses in AQP4+NMOSD and MOGAD and suggests different pathologic mechanisms of relapse-free neurological damage between MS and AQP4+NMOSD/MOGAD.
MeSH term(s)	Humans ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica/diagnostic imaging ; Retrospective Studies ; Recurrence ; Immunoglobulin G ; Aquaporin 4 ; Autoantibodies
Chemical Substances	Myelin-Oligodendrocyte Glycoprotein ; Immunoglobulin G ; Aquaporin 4 ; Autoantibodies
Language	English
Publishing date	2023-10-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2023.105093
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Article ; Online: Serum neurofilament light in MS: The first true blood-based biomarker?

Thebault, Simon / Bose, Gauruv / Booth, Ronald / Freedman, Mark S

Multiple sclerosis (Houndmills, Basingstoke, England)

2021 Volume 28, Issue 10, Page(s) 1491–1497

Abstract: A simple blood-derived biomarker is desirable in the routine management of multiple sclerosis (MS) patients and serum neurofilament light chain (sNfL) is the most promising candidate. Although its utility was first shown in cerebrospinal fluid (CSF), ... ...

Abstract	A simple blood-derived biomarker is desirable in the routine management of multiple sclerosis (MS) patients and serum neurofilament light chain (sNfL) is the most promising candidate. Although its utility was first shown in cerebrospinal fluid (CSF), technological advancements have enabled reliable detection in serum and less frequently plasma, obviating the need for repeated lumbar punctures. In this review, after defining the knowledge gap in MS management that many hope sNfL could fill, we summarize salient studies demonstrating associations of sNfL levels with outcomes of interest. We group these outcomes into inflammatory activity, progression, treatment response, and prediction/prognosis. Where possible we focus on data from real-world perspective observational cohorts. While acknowledging the limitations of sNfL and highlighting key areas for ongoing work, we conclude with our opinion of the role for sNfL as an objective, convenient, and cost-effective adjunct to clinical assessment. Paving the way for other promising biomarkers both blood-derived and otherwise, sNfL is an incremental step toward precision medicine for MS patients.
MeSH term(s)	Biomarkers/blood ; Humans ; Intermediate Filaments/metabolism ; Longitudinal Studies ; Multiple Sclerosis/diagnosis ; Neurofilament Proteins/blood ; Prognosis
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2021-02-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458521993066
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Article ; Online: A real-world single-centre analysis of alemtuzumab and cladribine for multiple sclerosis.

Bose, Gauruv / Rush, Carolina / Atkins, Harold L / Freedman, Mark S

Multiple sclerosis and related disorders

2021 Volume 52, Page(s) 102945

Abstract: Background: Highly active MS may warrant higher efficacy treatments for disease control. However, these often confer more risk and have not been compared in head-to-head clinical trials, making relative efficacy and safety difficult to interpret. ... ...

Abstract	Background: Highly active MS may warrant higher efficacy treatments for disease control. However, these often confer more risk and have not been compared in head-to-head clinical trials, making relative efficacy and safety difficult to interpret. Alemtuzumab and cladribine are two high-efficacy treatments given as discrete courses separated by one year, followed by a durable response that potentially does not require ongoing treatment. Before the approval of oral cladribine, our centre had been treating patients with a bioequivalent intravenous (IV) regimen since 2010. The objective of this study is to report the safety and efficacy data of alemtuzumab and cladribine in a real-world, single centre setting. Methods: We retrospectively reviewed all patients treated with alemtuzumab or cladribine at the Ottawa Hospital MS Clinic with 2 or more years of follow-up. Information on baseline demographic variables, previous treatment, and prior disease activity was collected. Outcomes investigated were "no evidence of disease activity" (NEDA) and its constituents: new clinical relapse, new MRI activity, and Expanded Disability Status Scale (EDSS) progression; as well as any adverse events or treatment discontinuation. We performed univariate and multiple logistic regression to determine differences in 2-year NEDA and time-to-event analyses with Cox regression models to determine factors associated with each outcome through the study period. Results: Forty-six patients were treated with alemtuzumab and 65 with cladribine of whom 51 (78%) received the intravenous regimen, followed for a total of 420.1 person-years. The cladribine group was older (p=.0002), with higher baseline EDSS (p=.0015), and more likely secondary progressive (p<.0001). Alemtuzumab had a higher rate of 2-year NEDA than cladribine (OR 4.78, 95%CI: 1.57-14.50, p=.006), but beyond 2 years the difference was not statistically significant (HR 0.50, 95%CI: 0.25-1. 30, p=.061). More prior treatments were associated with lower likelihood of retaining NEDA (HR 1.26, 95%CI: 1.03-1.54, p=.027). Alemtuzumab had more infusion reactions (80% vs. 17%, p<.0001), shingles (22% vs. 2%, p=.005), and secondary autoimmunity (52% vs. 3%, p<.0001) than cladribine, but there was no difference in grade 3 or higher adverse events (21.7% vs. 18.5%, p=1.0). Conclusion: In our cohort alemtuzumab and cladribine achieved similar rates of NEDA in long-term follow-up, with overall less adverse events with cladribine. Patient registries would allow more robust comparisons, detection of adverse events, and assessment of a durable response.
MeSH term(s)	Alemtuzumab ; Cladribine ; Humans ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting ; Neoplasm Recurrence, Local ; Retrospective Studies
Chemical Substances	Alemtuzumab (3A189DH42V) ; Cladribine (47M74X9YT5)
Language	English
Publishing date	2021-04-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2021.102945
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Article ; Online: Increasing Neurofilament and Glial Fibrillary Acidic Protein After Treatment Discontinuation Predicts Multiple Sclerosis Disease Activity.

Bose, Gauruv / Healy, Brian C / Saxena, Shrishti / Saleh, Fermisk / Glanz, Bonnie I / Bakshi, Rohit / Weiner, Howard L / Chitnis, Tanuja

Neurology(R) neuroimmunology & neuroinflammation

2023 Volume 10, Issue 6

Abstract: Background and objectives: Stable patients with multiple sclerosis (MS) may discontinue treatment, but the risk of disease activity is unknown. Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are biomarkers of ... ...

Abstract	Background and objectives: Stable patients with multiple sclerosis (MS) may discontinue treatment, but the risk of disease activity is unknown. Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are biomarkers of subclinical disease activity and may help risk stratification. In this study, sNfL and sGFAP levels in stable patients were evaluated before and after treatment discontinuation to determine association with disease activity. Methods: This observational study included patients enrolled in the Comprehensive Longitudinal Investigation in MS at the Brigham and Women's Hospital who discontinued treatment after >2 years disease activity-free. Two serum samples within 2 years, before and after treatment stop, were sent for sNfL and sGFAP measurements by single-molecule array. Biannual neurologic examinations and yearly MRI scans determined disease activity by 3 time-to-event outcomes: 6-month confirmed disability worsening (CDW), clinical attacks, and MRI activity (new T2 or contrast-enhancing lesions). Associations between each outcome and log-transformed sNfL and sGFAP levels pretreatment stop and posttreatment stop and the percent change were estimated using multivariable Cox regression analysis adjusting for age, disability, disease duration, and duration from attack before treatment stop. Results: Seventy-eight patients (92% female) discontinued treatment at a median (interquartile range) age of 48.5 years (39.0-55.7) and disease duration of 12.3 years (7.5-18.8) and were followed up for 6.3 years (4.2-8.5). CDW occurred in 27 patients (35%), new attacks in 19 (24%), and new MRI activity in 26 (33%). Higher posttreatment stop sNfL level was associated with CDW (adjusted hazard ratio (aHR) 2.80, 95% CI 1.36-5.76, Discussion: Stable patients who discontinue treatment may be risk stratified by sNfL and sGFAP levels measured before and after discontinuing treatment. Further studies are needed to validate findings and determine whether resuming treatment in patients with increasing biomarker levels reduces risk of subsequent disease activity.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/drug therapy ; Intermediate Filaments/metabolism ; Intermediate Filaments/pathology ; Glial Fibrillary Acidic Protein/metabolism ; Biomarkers ; Magnetic Resonance Imaging
Chemical Substances	Glial Fibrillary Acidic Protein ; Biomarkers
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200167
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Article ; Online: Early miR-320b and miR-25-3p miRNA levels correlate with multiple sclerosis severity at 10 years: a cohort study.

Gonzalez-Martinez, Alicia / Bose, Gauruv / Lokhande, Hrishikesh / Saxena, Shrishti / Healy, Brian C / Polgar-Turcsanyi, Mariann / Weiner, Howard L / Chitnis, Tanuja

Journal of neuroinflammation

2023 Volume 20, Issue 1, Page(s) 136

Abstract: Background: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of ... ...

Abstract	Background: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. Main body: We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. Conclusions: Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.
MeSH term(s)	Humans ; Female ; Adult ; Male ; MicroRNAs/genetics ; Multiple Sclerosis/genetics ; Cohort Studies ; Brain ; Biomarkers
Chemical Substances	MicroRNAs ; Biomarkers ; MIRN486 microRNA, human ; MIRN25 microRNA, human
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-023-02816-8
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