Multiple sclerosis New Drugs Review
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Multiple Sclerosis--the vascular connection: The brain contains 400 miles of blood vessels....

Multiple Sclerosis--the vascular connection: The brain contains 400 miles of blood vessels.... | Multiple sclerosis New Drugs Review | Scoop.it
A year after Jeff was diagnosed with Multiple Sclerosis, I wrote several university researchers regarding MS as a vascular disease o
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Daclizumab (Biogen, Abbott) Review: Multiple sclerosis - Krishan Maggon

Daclizumab (Biogen, Abbott) Review: Multiple sclerosis - Krishan Maggon | Multiple sclerosis New Drugs Review | Scoop.it
Daclizumab is a humanized monoclonal antibody which targets the CD25 alpha subunit of the high affinity receptor and inhibits...
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JCI Insight - Longitudinally persistent cerebrospinal fluid B-cells can resist treatment in multiple sclerosis

JCI Insight - Longitudinally persistent cerebrospinal fluid B-cells can resist treatment in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it

B-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. We sought to investigate the presence of clonally related B-cells over time by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1.2 (+/-0.3 SD) years later during the second sampling. We found clonal persistence of B-cells in the CSF of five patients; these B-cells were frequently immunoglobulin (Ig) class-switched and CD27+. We identified specific blood B-cell subsets that appear to provide input into CNS repertoires over time. We demonstrate complex patterns of clonal B-cell persistence in CSF and blood, even in patients on immune modulating therapy. Our findings support the concept that peripheral B-cell activation and CNS-compartmentalized immune mechanisms can in part therapy-resistant.

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Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers

Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers | Multiple sclerosis New Drugs Review | Scoop.it
Many conditions mimic MS, and despite validated diagnostic criteria (Thompson et al.,
2018), accurate diagnosis can be challenging. Patients without MS are commonly misdiagnosed
with MS. Though many MS specialists routinely identify misdiagnoses (Solomon et al., 2012), a problem acknowledged in...
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Erdheim–Chester disease mimicking multiple sclerosis or a new association?

Erdheim–Chester disease mimicking multiple sclerosis or a new association? | Multiple sclerosis New Drugs Review | Scoop.it
A 53-year-old man was admitted to our department for paroxysmal episodes of paresthesia
in the legs associated with painful contraction of the extremities lasting seconds.
The results of the initial neurological examination were normal.
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We sincerely apologize, but you don’t have MS –

We sincerely apologize, but you don’t have MS – | Multiple sclerosis New Drugs Review | Scoop.it
The rate of misdiagnosis of MS around the globe is roughly a quarter. We are so focused in making an early diagnosis in MS that before we know it, it’s a runaway train.Sometimes, even the be…...
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Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study

Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study | Multiple sclerosis New Drugs Review | Scoop.it
Neurosurgery 84:499-505, 2019 Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal.No large p…...
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Monomethyl Fumarate Challenges Multiple Sclerosis

Monomethyl Fumarate Challenges Multiple Sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
A novel bioequivalent of dimethyl fumarate (Tecfidera) may soon be offering another treatment option for patients with multiple sclerosis. ...
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Approved Beta Interferons in Relapsing-Remitting Multiple Sclerosis: Is there an odd one Out? - Alexis Clapin, 2012

Approved Beta Interferons in Relapsing-Remitting Multiple Sclerosis: Is there an odd one Out? - Alexis Clapin, 2012 | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Three interferons are marketed for the treatment of relapsing-remitting multiple sclerosis. In its pivotal trial, one of them demonstrated impressive efficacy as a once-weekly regimen, but later head-to-head studies and reviews questioned its superiority. Analysis of this pivotal trial in publications and health authority reviews has shown that its early termination might have caused attrition bias. Censored patients were different from those completing the study on magnetic resonance imaging parameters and benefited from placebo in terms of relapse rate. Early progression of disability and differences in follow-up duration could have favored the benefit observed for the progression of disability outcome. Only the raw data could be of help to confirm or refute doubts about this trial. Raw data should be made available to the scientific community.

Keywords interferons, relapsing-remitting multiple sclerosis, efficacy
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Remyelination promoting therapies in multiple sclerosis animal models: a systematic review and meta-analysis

Remyelination promoting therapies in multiple sclerosis animal models: a systematic review and meta-analysis | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
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Intereye RNFL differences useful for predicting optic nerve lesion in multiple sclerosis

Intereye RNFL differences useful for predicting optic nerve lesion in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
The optic nerve is a frequent site for involvement in multiple sclerosis (MS).Using OCT, the authors sought to determine optimal thresholds for intereye differ...
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Biogen beats estimates on multiple sclerosis drugs sales | Reuters

Biogen beats estimates on multiple sclerosis drugs sales | Reuters | Multiple sclerosis New Drugs Review | Scoop.it
Biogen Inc beat analysts' estimates for fourth-quarter profit and revenue o...
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Culturing technique captures hard-to-study, critically important brain cell — the oligodendrocyte — in action

Culturing technique captures hard-to-study, critically important brain cell — the oligodendrocyte — in action | Multiple sclerosis New Drugs Review | Scoop.it
Fat-filled brain cells called oligodendrocytes wrap their flab around neurons, vastly enhancing signal transmission. Crucial, but tough to study until now.
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Altered human oligodendrocyte heterogeneity in multiple sclerosis

Altered human oligodendrocyte heterogeneity in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
We identified sub-clusters of oligodendroglia in Ctr human WM, some similar to mouse, and defined new markers for these cell states. Strikingly, some sub-clusters were under-represented in MS tissue, while others were more prevalent. These differences in mature OL sub-clusters may indicate different functional states of OLs in MS lesions. Since this is similar in normal appearing white matter (NAWM), MS is a more diffuse disease than its focal demyelination suggests. Our findings of an altered oligodendroglial heterogeneity in MS may be important to understanding disease progression and developing therapeutic approaches.
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Promising Stem Cell Therapy For Multiple Sclerosis - CBS Chicago

Promising Stem Cell Therapy For Multiple Sclerosis - CBS Chicago | Multiple sclerosis New Drugs Review | Scoop.it
An experimental treatment for multiple sclerosis is showing promise in stopping symptoms of the disease, according to a new study that found that a single stem cell transplant could stop or delay symptoms better than some medications.
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Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis

Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) has a severe impact on patients’ quality of life (QoL) and
affects their functionality in numerous ways. Physical disability and upper extremity function can restrict the daily routine considerably and have been shown to correlate with measures of QoL (Van Schependom...
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Natalizumab in secondary progressive multiple sclerosis

Natalizumab in secondary progressive multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Although several disease-modifying treatments are available for relapsing types of
multiple sclerosis, additional treatment options for progressive types of multiple
sclerosis are needed, especially since the available treatments tend to focus on patients
who are actively relapsing.
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Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement

Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement | Multiple sclerosis New Drugs Review | Scoop.it
Leptomeningeal inflammation was described in patients with secondary progressive multiple
sclerosis (SPMS) in 2004 and has subsequently been identified at all stages of the
disease (Howell et al., 2011; Lucchinetti et al., 2011; Magliozzi et al., 2007; Serafini
et al., 2004).
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Health information work and the enactment of care in couples and families affected by Multiple Sclerosis - Mazanderani - 2019 - Sociology of Health & Illness - Wiley Online Library

Abstract

Given the considerable emphasis placed on informed choice, the management of health information has become an increasingly important part of living with chronic illness. This paper explores the intra‐familial dynamics of managing health information in the context of chronic illness. Drawing on 77 interviews with people affected by Multiple Sclerosis in the UK (patients, partners, family members and close friends), we show how families develop their own idiosyncratic information practices, including the careful, at times strategic, seeking, sharing and withholding of information. We describe how one individual, most commonly either the patient or their partner, often takes primary responsibility for managing growing quantities of health information. Doing this is a complex task, yet its dynamics within the family unit remain invisible and unacknowledged. In this paper we: (a) stress the importance of understanding information management in chronic illness as a collective process across all those affected, patients as well as carers; (b) conceptualise the process of managing health information in this context as ‘health information work’; and (c) analyse it as part of the wider care practices families engage in and as a form of care in its own right.

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The prodrome in relapsing remitting and primary progressive multiple sclerosis - Wijnands - - European Journal of Neurology - Wiley Online Library

The prodrome in relapsing remitting and primary progressive multiple sclerosis - Wijnands - - European Journal of Neurology - Wiley Online Library | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
We examined the existence of a prodrome in relapsing‐onset multiple sclerosis (RMS) and primary progressive MS (PPMS) by comparing the number of physician encounters (via International Classification of Diseases diagnoses and physician speciality) in the five years before symptom onset in 1,887 RMS, 171 PPMS cases, and 9,837 matched population controls. Negative binomial regression models were sex, age, socioeconomic status and calendar year adjusted. Compared to RMS cases, PPMS cases had more nervous system‐related encounters (adjusted rate ratio [aRR]=3.00;95%CI:1.06‐8.49) and fewer encounters with dermatologists (aRR=0.53;95%CI:0.30‐0.96). Findings suggest that RMS and PPMS cases may both experience a prodrome, although aspects differ.
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Response to: Comment on “Transorbital ultrasonography for measuring optic nerve atrophy in multiple sclerosis” - Candeliere Merlicco - - Acta Neurologica Scandinavica - Wiley Online Library

Response to: Comment on “Transorbital ultrasonography for measuring optic nerve atrophy in multiple sclerosis” - Candeliere Merlicco - - Acta Neurologica Scandinavica - Wiley Online Library | Multiple sclerosis New Drugs Review | Scoop.it
Reply Response to: Comment on “Transorbital ultrasonography for measuring optic nerve atrophy in multiple sclerosis” Laura Gabaldón Torres Isidoro Fernández Romero Eladio Aparicio Castro First published: 05 February 2019 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ane.13076 You do not have access to the full version of this article.View access options below. Institutional Login Log in with Open Athens, Shibboleth, or your institutional credentials. If you have previously obtained access with your personal account, Please log in. Abstract We thank the authors for the comments on our recent work (1) and we would offer some clarification. The blooming effect is a doppler imaging artifact (2). In our work the doppler mode has not been used, so it is not possible that the blooming effect could artifact the images. On the other hand, we have already commented that, the difficulty in correctly visualizing all the structures that make up the optic nerve (ON) is one of the limitations of transorbital ultrasound, but we doubt that the use of the A‐mode can be of any help. This article is protected by copyright. All rights reserved. Accepted Articles Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future.
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Frontiers | The Effect of Disease Modifying Therapies on Disability Progression in Multiple Sclerosis: A Systematic Overview of Meta-Analyses | Neurology

Frontiers | The Effect of Disease Modifying Therapies on Disability Progression in Multiple Sclerosis: A Systematic Overview of Meta-Analyses | Neurology | Multiple sclerosis New Drugs Review | Scoop.it
Background: Disease modifying therapy (DMT) efficacy trials make an essential contribution to the development of evidence-based clinical treatments and practices for people with multiple sclerosis (MS). Meta-analysis is a critical part of this process and provides a powerful tool to assess the effects of DMT on MS progression. However, although there have been several meta-analyses on the effect of DMT on MS disease progression, they often do not reach the same conclusions.

Objective: Our aim was to better understand and contextualize the results of meta-analyses evaluating DMT, identify differences in methodology that might explain their differing conclusions, and highlight areas for future research that will improve our ability to develop clinical recommendations.

Methods: We conducted an overview of systematic reviews with meta-analyses assessing the efficacy of DMT on disability progression in people with MS in PubMed (Medline) and the Cochrane Database of Systematic Reviews.

Results: We included 22 meta-analyses in this overview: eight general (on >3 DMT), 11 specific (on ≤3 DMT), 2 that evaluated subsets, and 1 that evaluated long-term effects. We found that there is good evidence that DMT improve short-term (≤2–3 years) disability progression outcomes relative to placebo in people with relapsing-remitting MS. However, results varied substantially between meta-analyses, and there is little evidence of their efficacy in other populations or over longer periods. The relative effects of individual DMT also remain unclear. The variance in results between meta-analyses may be related to the substantial differences in inclusion criteria, which was reflected in the limited overlap in included studies, as well as the year of meta-analysis publication. Of the 123 total unique studies included in the general meta-analyses, 77 (62.6%) were included in only one meta-analysis. This incongruence was also evident in the included DMT. Six of the 16 (37.5%) DMT evaluated in the general meta-analyses were only included in one meta-analysis.

Conclusions: Translating DMT efficacy studies into evidence-based clinical practice requires greater methodological consistency in meta-analyses, more data on the relative effects of DMT through head-to-head clinical trials, and better reporting of adverse events.
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Intereye RNFL differences useful for predicting optic nerve lesion in multiple sclerosis

Intereye RNFL differences useful for predicting optic nerve lesion in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
The optic nerve is a frequent site for involvement in multiple sclerosis (MS).Using OCT, the authors sought to determine optimal thresholds for intereye differ...
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Fumarates target the metabolic-epigenetic interplay of brain-homing T cells in multiple sclerosis | Brain | Oxford Academic

Fumarates target the metabolic-epigenetic interplay of brain-homing T cells in multiple sclerosis | Brain | Oxford Academic | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Cell-permeable formulations of metabolites, such as fumaric acid esters, have been used as highly effective immunomodulators in patients with multiple sclerosis and yet their mechanism of action remains elusive. Since fumaric acid esters are metabolites, and cell metabolism is highly intertwined with the epigenetic regulation of gene expression, we investigated whether this metabolic-epigenetic interplay could be leveraged for therapeutic purposes. To this end we recruited 47 treatment-naïve and 35 fumaric acid ester-treated patients with multiple sclerosis, as well as 16 glatiramer acetate-treated patients as a non-metabolite treatment control. Here we identify a significant immunomodulatory effect of fumaric acid esters on the expression of the brain-homing chemokine receptor CCR6 in CD4 and CD8 T cells of patients with multiple sclerosis, which include T helper-17 and T cytotoxic-17 cells. We report differences in DNA methylation of CD4 T cells isolated from untreated and treated patients with multiple sclerosis, using the Illumina EPIC 850K BeadChip. We first demonstrate that Krebs cycle intermediates, such as fumaric acid esters, have a significantly higher impact on epigenome-wide DNA methylation changes in CD4 T cells compared to amino-acid polymers such as glatiramer acetate. We then define a fumaric acid ester treatment-specific hypermethylation effect on microRNA MIR-21, which is critical for the differentiation of T helper-17 cells. This hypermethylation effect was attributed to the subpopulation of T helper-17 cells using a decomposition analysis and was further validated in an independent prospective cohort of seven patients before and after treatment with fumaric acid esters. In vitro treatment of CD4 and CD8 T cells with fumaric acid esters supported a direct and dose-dependent effect on DNA methylation at the MIR-21 promoter. Finally, the upregulation of miR-21 transcripts and CCR6 expression was inhibited if CD4 or CD8 T cells stimulated under T helper-17 or T cytotoxic-17 polarizing conditions were treated with fumaric acid esters in vitro. These data collectively define a direct link between fumaric acid ester treatment and hypermethylation of the MIR-21 locus in both CD4 and CD8 T cells and suggest that the immunomodulatory effect of fumaric acid esters in multiple sclerosis is at least in part due to the epigenetic regulation of the brain-homing CCR6+ CD4 and CD8 T cells.

multiple sclerosis, DNA methylation, fumaric acid esters, CD4 T cells, metabolic-epigenetic interplay
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The Out-of-Pocket Cost Burden for Specialty Drugs in Medicare Part D in 2019

The Out-of-Pocket Cost Burden for Specialty Drugs in Medicare Part D in 2019 | Multiple sclerosis New Drugs Review | Scoop.it
Medicare Part D has helped to make prescription drugs more affordable for people with Medicare, yet many beneficiaries continue to face high out-of-pocket costs for their medications.Specialty tie…...
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Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis

Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) is a chronic autoimmune disease, characterized by inflammation
of the central nervous system that leads to progressive neuro-axonal degeneration
(Lavery et al., 2014). There is no cure for MS, but 14 disease-modifying therapies (DMTs; following the withdrawal of daclizumab...
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Myelin oligodendrocyte glycoprotein immunoglobulin G‐associated disease: An overview - Fujihara - 2018 - Clinical and Experimental Neuroimmunology - Wiley Online Library

Abstract

 

Myelin oligodendrocyte glycoprotein (MOG) is localized at the outermost layer of the myelin sheath and is accessible for autoantibodies. Although experimental autoimmune encephalitis induced with MOG immunization has been studied for 30 years, the results of previous reports on MOG immunoglobulin G (IgG) detection with enzyme‐linked immunosorbent assay and Western blot are confusing. However, after the development of human MOG‐transfected cell‐based assay to detect conformational‐sensitive MOG‐IgG, unique groups of patients have been found seropositive, and MOG‐IgG‐associated disease has become a hot topic in clinical neuroimmunology. Currently, the clinical spectrum of MOG‐IgG‐associated disease includes idiopathic optic neuritis, acute disseminated encephalomyelitis, encephalitides (brainstem and cerebral cortical), idiopathic myelitis, atypical multiple sclerosis, aquaporin‐4 IgG‐negative neuromyelitis optica spectrum disorders and others. MOG‐IgG‐associated disease occurs in both children and adults, and the female:male ratio is almost 1:1. Pleocytosis in the cerebrospinal fluids during acute exacerbation is often seen, but oligoclonal IgG bands are usually negative. T helper cell 17, B cells and neutrophil‐related cytokines appear to be upregulated intrathecally. The pathology of acute lesions is characterized by active inflammation demyelination with deposition of immunoglobulins and complements. Just like aquaporin 4 IgG‐positive neuromyelitis optica spectrum disorders, some disease‐modifying drugs for multiple sclerosis seem to be inefficacious in MOG‐IgG‐associated disease, and chronic immunosuppression is required to prevent relapse, especially in patients persistently positive for MOG‐IgG. Our understanding of this newly recognized disease remains insufficient, and the progress of research is much expected.

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