Multiple sclerosis New Drugs Review
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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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Is It OK to publish ten years later..This time its cladribine –

Is It OK to publish ten years later..This time its cladribine – | Multiple sclerosis New Drugs Review | Scoop.it
Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis.Comi G, Cook S, Giovannoni G, Rieckmann P, Sørensen PS, Vermersch P, Gal…...
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BMI, but not age at puberty, tied to risk of multiple sclerosis

BMI, but not age at puberty, tied to risk of multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Some studies have suggested that people who are younger when they enter puberty are more likely to later develop multiple sclerosis (MS). But a new study attributes that link to body mass index (BMI).
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Carnitine for fatigue in multiple sclerosis - Tejani, AM - 2012 | Cochrane Library

Carnitine for fatigue in multiple sclerosis - Tejani, AM - 2012 | Cochrane Library | Multiple sclerosis New Drugs Review | Scoop.it
Cochrane Database of Systematic Reviews Abstract available in Background Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. Objectives To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS‐related fatigue and to identify any adverse effects of carnitine when used for this purpose. Search methods A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966‐09 September 2011), EMBASE (1974‐09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Selection criteria Full reports of published and unpublished randomized controlled trials and quasi‐randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data collection and analysis Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention‐to‐treat analysis and completeness of follow up. Main results The search identified one ongoing randomized, placebo‐controlled, cross‐over trial (expected completion 2013) and one completed randomized, active‐comparator, cross‐over trial. In the completed study, adult patients with relapsing‐remitting and secondary progressive MS were exposed to both acetyl L‐carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported. Authors' conclusions There is insufficient evidence that carnitine for the treatment of MS‐related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity. Plain language summary available in Carnitine for fatigue in patients with multiple sclerosis (MS) Fatigue  is commonly associated with multiple sclerosis and leads to significant disability and loss of quality of life. Several kind of interventions have been carried out, but definitive evidence on their relative efficacy and tolerability are not available.  As quite recently it has been hypothesised a relationship between low carnitine levels in the blood and fatigue, and several studies showed that supplementation with carnitine produced improvement in fatigue symptoms. The Authors decided to perform a systematic review to assess the possible efficacy of carnitine in improving fatigue and to identify any adverse events in relapsing‐remitting and secondary progressive MS patients. Most of the studies did not meet the inclusion criteria of methodological  quality, but one with the enrollement of  36 patients for 12‐month intervention  with carnitine associated with amantadine, another drug commonly used to improve fatigue. From this report, it is unclear if carnitine supplementation in MS patients improves fatigue, reduces the disability that results from fatigue or improves quality of life. It is also unclear if the use of carnitine for MS related fatigue is safe. Unlock the full review
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DNA methylation in demyelinated multiple sclerosis hippocampus

DNA methylation in demyelinated multiple sclerosis hippocampus | Multiple sclerosis New Drugs Review | Scoop.it
Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased. Comparative methylation profiling identify hypo-methylation within upstream sequences of 6 genes and hyper-methylation of 10 genes in demyelinated MS hippocampus. Genes identified in the current study were also validated in an independent microarray dataset generated from MS hippocampus. Independent validation using RT-PCR revealed that DNA methylation inversely correlated with mRNA levels of the candidate genes. Queries across cell-specific databases revealed that a majority of the candidate genes are expressed by astrocytes and neurons in mouse and human CNS. Taken together, our results expands the list of genes previously identified in MS hippocampus and establish DNA methylation as a mechanism of altered gene expression in MS hippocampus.
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Common treatment for multiple sclerosis may prolong life

Common treatment for multiple sclerosis may prolong life | Multiple sclerosis New Drugs Review | Scoop.it
Researchers from the University of British Columbia and Vancouver Coastal Health Research Institute have found that a widely prescribed drug for multiple sclerosis (MS) is associated with longer survival for patients.
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Biomedicines | Free Full-Text | Monoclonal Antibodies in Multiple Sclerosis: Present and Future | HTML

Biomedicines | Free Full-Text | Monoclonal Antibodies in Multiple Sclerosis: Present and Future | HTML | Multiple sclerosis New Drugs Review | Scoop.it
Abstract: The global incidence of multiple sclerosis (MS) appears to be increasing. Although it may not be associated with a high mortality rate, this disease has a high morbidity rate which affects the quality of life of patients and reduces their ability to do their activities of daily living. Thankfully, the development of novel disease modifying therapies continues to increase. Monoclonal antibodies (MABs) have become a mainstay of MS treatment and they are likely to continue to be developed for the treatment of this disease. Specifically, MABs have proven to be some of the most efficacious treatments at reducing relapses and the inflammation in MS patients, including the first treatment for primary progressive MS and are being explored as reparative/remyelinating agents as well. These relatively new treatments will be reviewed here to help evaluate their efficacy, adverse events, immunogenicity, and benefit-risk ratios in the treatment of the diverse spectrum of MS. The focus will be on MABs that are currently approved or may be approved in the near future.
Keywords: monoclonal antibodies; anti-CD20; Ocrevus; Rituxan; Tysabri; multiple sclerosis; clinical trial; disease modifying therapy
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Leptomeningeal Contrast Enhancement Is Related to Focal Cortical Thinning in Relapsing-Remitting Multiple Sclerosis: A Cross-Sectional MRI Study

Leptomeningeal Contrast Enhancement Is Related to Focal Cortical Thinning in Relapsing-Remitting Multiple Sclerosis: A Cross-Sectional MRI Study | Multiple sclerosis New Drugs Review | Scoop.it
Differences between ipsilateral and contralateral ROIs progressively decreased with larger ROIs, but no significant effects were detected when considering the entire MS sample. In patients with relapsing-remitting MS only, significantly reduced cortical thickness was found for 5 dilations (−8.53%, corrected P = .04) and 10 dilations (−5.20%, corrected P = .044).

CONCLUSIONS: Focal leptomeningeal contrast enhancement is associated with reduced thickness of the surrounding cortex in patients with relapsing-remitting MS, but not in those with secondary-progressive MS. Our results suggest that pathology associated with the presence of leptomeningeal contrast-enhancement foci has a stronger, localized effect on cortical tissue loss earlier in the disease.
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The monoclonal antibody GNbAC1: targeting human endogenous retroviruses in multiple sclerosis

The monoclonal antibody GNbAC1: targeting human endogenous retroviruses in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Background:
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS). Despite improvements of immunomodulatory therapies in relapsing–remitting MS, the pathomechanisms of progressive disease are poorly understood and therapeutically addressed to date. A pathophysiological role for proteins encoded by human endogenous retroviruses (HERVs) has been proposed. GNbAC1 is a monoclonal antibody directed against the envelope protein of a HERV with postulated involvement in MS.

Methods:
This review addresses the treatment concept of GNbAC1, the design, preclinical and clinical development of the antibody, as published by November 2018. All four in-human trials (of which two addressed MS) are discussed.

Conclusion:
The treatment concept of GNbAC1 is appealing but remains controversial due to conflicting results regarding the hypothesized underlying pathomechanism. Anticipated immunomodulatory effects were not observed in clinical or pharmacodynamic analyses of the currently available data. However, a magnetic resonance imaging sign compatible with the remyelinating potential of GNbAC1 encouraged further development of this antibody in progressive MS. No relevant issues with tolerability or safety have been described to date.

Keywords: relapsing multiple sclerosis, progressive multiple sclerosis, human endogenous retrovirus, monoclonal antibody, GNbAC1
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Overview of Demyelinating Disorders - Brain, Spinal Cord, and Nerve Disorders

Overview of Demyelinating Disorders - Brain, Spinal Cord, and Nerve Disorders | Multiple sclerosis New Drugs Review | Scoop.it
Overview of Demyelinating Disorders - Learn about the causes, symptoms, diagnosis & treatment from the Merck Manuals - Medical Consumer Version.
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The benefits of neuroinflammation for the repair of the injured central nervous system

The benefits of neuroinflammation for the repair of the injured central nervous system | Multiple sclerosis New Drugs Review | Scoop.it
Inflammation of the nervous system (neuroinflammation) is now recognized as a hallmark of virtually all neurological disorders. In neuroinflammatory conditions such as multiple sclerosis, there is prominent infiltration and a long-lasting representation of various leukocyte subsets in the central nervous system (CNS) parenchyma. Even in classic neurodegenerative disorders, where such immense inflammatory infiltrates are absent, there is still evidence of activated CNS-intrinsic microglia. The consequences of excessive and uncontrolled neuroinflammation are injury and death to neural elements, which manifest as a heterogeneous set of neurological symptoms. However, it is now readily acknowledged, due to instructive studies from the peripheral nervous system and a large body of CNS literature, that aspects of the neuroinflammatory response can be beneficial for CNS outcomes. The recognized benefits of inflammation to the CNS include the preservation of CNS constituents (neuroprotection), the proliferation and maturation of various neural precursor populations, axonal regeneration, and the reformation of myelin on denuded axons. Herein, we highlight the benefits of neuroinflammation in fostering CNS recovery after neural injury using examples from multiple sclerosis, traumatic spinal cord injury, stroke, and Alzheimer’s disease. We focus on CNS regenerative responses, such as neurogenesis, axonal regeneration, and remyelination, and discuss the mechanisms by which neuroinflammation is pro-regenerative for the CNS. Finally, we highlight treatment strategies that harness the benefits of neuroinflammation for CNS regenerative responses.
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GeNeuro's Drug Blocking Hidden Viral Protein Shows Promise for Treating Multiple Sclerosis

GeNeuro's Drug Blocking Hidden Viral Protein Shows Promise for Treating Multiple Sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
An antibody that blocks the action of a hidden viral protein encoded by our genome shows encouraging signs of slowing down the progression of multiple sclerosis, according to the Swiss biotech GeNeuro which carried out the research.
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Alemtuzumab | Multiple Sclerosis Society UK

Alemtuzumab | Multiple Sclerosis Society UK | Multiple sclerosis New Drugs Review | Scoop.it
Alemtuzumab (it's brand name is lemtrada) is recommended for the treatment of 'active' relapsing MS.
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Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol

Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol | Multiple sclerosis New Drugs Review | Scoop.it
Evidence-based pharmacological and behavioral interventions are often underutilized
or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or
depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality...
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Clever math enables MRI to map molecules implicated in multiple sclerosis, other diseases

Clever math enables MRI to map molecules implicated in multiple sclerosis, other diseases | Multiple sclerosis New Drugs Review | Scoop.it
New techniques wring subtle signals from data already produced by scanners...
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Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Abstract BACKGROUND:: In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated. OBJECTIVES:: The aim of this study was to assess the dynamic resting state (RS) functional connectivity (FC) on 62 relapsing-remitting MS patients and 65 sex-matched healthy controls enrolled at 7 European sites. METHODS:: MS patients underwent clinical and cognitive evaluation. Between-group network FC differences were evaluated using a dynamic approach (based on sliding-window correlation analysis) and grouping correlation matrices into recurrent FC states. RESULTS:: Dynamic FC analysis revealed, in healthy controls and MS patients, three recurrent FC states: two characterized by strong intra- and inter-network connectivity and one characterized by weak inter-network connectivity (State 3). A total of 23 MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI-MS patients had reduced RS-FC between subcortical and default-mode networks in the low-connectivity State 3 and lower dwell time (i.e. time spent in a given state) in the high-connectivity State 2. CI-MS patients lso exhibited a lower number and a less frequent switching between meta-states, as well as a smaller distance traveled through connectivity states. CONCLUSION: Time-varying RS-FC was markedly less dynamic in CI- versus CP-MS atients, suggesting that slow inter-network connectivity contributes to cognitive dysfunction in MS.
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Dimethyl Fumarate Disrupts Human Innate Immune Signaling by Targeting the IRAK4–MyD88 Complex

Dimethyl Fumarate Disrupts Human Innate Immune Signaling by Targeting the IRAK4–MyD88 Complex | Multiple sclerosis New Drugs Review | Scoop.it
KEY POINTS DMF suppresses cytokine production in pDCs. DMF blocks Myddosome formation by disrupting the MyD88–IRAK4 interaction. DMF blocks the MyD88–IRAK4 interaction by targeting C13 in IRAK4. Abstract Dimethyl fumarate (DMF) is a prescribed treatment for multiple sclerosis and has also been used to treat psoriasis. The electrophilicity of DMF suggests that its immunosuppressive activity is related to the covalent modification of cysteine residues in the human proteome. Nonetheless, our understanding of the proteins modified by DMF in human immune cells and the functional consequences of these reactions remains incomplete. In this study, we report that DMF inhibits human plasmacytoid dendritic cell function through a mechanism of action that is independent of the major electrophile sensor NRF2. Using chemical proteomics, we instead identify cysteine 13 of the innate immune kinase IRAK4 as a principal cellular target of DMF. We show that DMF blocks IRAK4–MyD88 interactions and IRAK4-mediated cytokine production in a cysteine 13–dependent manner. Our studies thus identify a proteomic hotspot for DMF action that constitutes a druggable protein–protein interface crucial for initiating innate immune responses. Footnotes This work was supported by the National Institutes of Health (Grant CA231991), a Life Science Research Foundation fellowship (to E.V.V.), the American Cancer Society (Fellowship PF-15-142-01-CDD to B.W.Z.), the National Science Foundation (Fellowship DGE-1346837 to M.M.B.), and The Donald E. and Delia B. Baxter Foundation Faculty Scholar Grant (to J.R.T.). The online version of this article contains supplemental material. Received December 26, 2018. Accepted February 26, 2019. Copyright © 2019 by The American Association of Immunologists, Inc.

Via Gilbert C FAURE
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Patient’s Risk Tolerance for Disease Modifying Treatments for Multiple Sclerosis<

Patient’s Risk Tolerance for Disease Modifying Treatments for Multiple Sclerosis< | Multiple sclerosis New Drugs Review | Scoop.it
Patient’s Risk Tolerance for Disease Modifying Treatments for Multiple Sclerosis   In a study published in Neurology, researchers at the Cleveland Clinic evaluated patients’ tolerance for potential risks of multiple sclerosis (MS) medications. Studies show that 40% or more of patients diagnosed with MS do not receive disease-modifying treatment (DMT) in the first 2 years after diagnosis. This is concerning because evidence-based practice guidelines recommend treating MS with DMTs as early as possible. Understanding what barriers to treatment exist, and why, are important steps to improving care and quality-of-life for patients with MS. Patients willingness to risk the side effects of any medication are among such barriers.  Researchers used an online survey to ask 3,176 people with MS if they would take a new medicine (50% effective at preventing relapse) with a risk that occurs at a rate of 1 in 1,000 people. If they answered yes, they were then asked if they would take it with a higher risk (eg, 1 in 100); if not, they were asked if they would at a lower risk (eg, 1 in 500). In this way individuals’ maximum tolerance for each of 6 side effects, known to occur with existing DMTs, were measured. The risks evaluated were: bladder or respiratory infections that occasionally require hospitalization,  thyroid injury that may require life-long daily medication,  rash serious enough to require hospitalization, liver problems that would require frequent blood testing,  kidney disease that could result in need for life-long dialysis, and  progressive multifocal leukoencephalopathy (PML) that could cause death.  Overall, survey respondents were more willing to risk infection or thyroid complications and least willing to risk kidney disease or PML. Overall risk tolerance increased with disability progression and prior use of DMTs (infusion > injection) but decreased with age. Male patients had high tolerance risk for infection, thyroid injury, rash, and liver problems (1 in 1,000) but not for kidney injury (1 in 50,000) or PML (1 in 100,000). Women were less likely to tolerate risk for all complications (1 in 2,000 for infection or thyroid injury; 1 in 1 million for kidney in or PML).  First author of the study, Robert J. Fox, MD of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic said, “we hope the study will help clinicians better understand where to initiate a conversation with a given patient—not that they should stereotype patients with this—rather that they begin at a place more likely to resonate with a particular patient and refine the conversation from there.”  Fox also noted that this information could help inform the assessments of risk-benefit analysis at a regulatory level because it “gives us quantified measurements of risk tolerance that can be used along with individual patient testimonies, which is all we’ve had available until now.”
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Does the environment influence multiple sclerosis pathogenesis via UVB light and/or induction of vitamin D?

Multiple sclerosis (MS) is a disease of presumed auto-immune origin. Long-standing observations such as the correlation between MS incidence and geographical latitude or the levels of Vitamin D (Vit D) in the serum have implicated the environmental factors UVB radiation and diet in the etiology of...
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TMEM10 Promotes Oligodendrocyte Differentiation and is Expressed by Oligodendrocytes in Human Remyelinating Multiple Sclerosis Plaques

TMEM10 Promotes Oligodendrocyte Differentiation and is Expressed by Oligodendrocytes in Human Remyelinating Multiple Sclerosis Plaques | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Oligodendrocyte precursor cells (OPCs) differentiate during postnatal development into myelin-forming oligodendrocytes, in a process distinguished by substantial changes in morphology and the onset of myelin gene expression. A mammalian-specific CNS myelin gene, tmem10, also called Opalin, encodes a type 1 transmembrane protein that is highly upregulated during early stages of OPC differentiation; however, a function for TMEM10 has not yet been identified. Here, consistent with previous studies, we detect TMEM10 protein in mouse brain beginning at ~P10 and show that protein levels continue to increase as oligodendrocytes differentiate and myelinate axons in vivo. We show that constitutive TMEM10 overexpression in the Oli-neu oligodendroglial cell line promotes the expression of the myelin-associated genes MAG, CNP and CGT, whereas TMEM10 knock down in primary OPCs reduces CNP mRNA expression and decreases the percentage of MBP-positive oligodendrocytes that differentiate in vitro. Ectopic TMEM10 expression evokes an increase in process extension and branching, and blocking endogenous TMEM10 expression results in oligodendrocytes with abnormal cell morphology. These findings may have implications for human demyelinating disorders, as oligodendrocytes expressing TMEM10 are detected in human remyelinating multiple sclerosis lesions. Together, our findings provide evidence that TMEM10 promotes oligodendrocyte terminal differentiation and may represent a novel target to promote remyelination in demyelinating disorders.
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JCM | Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study

JCM | Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study | Multiple sclerosis New Drugs Review | Scoop.it
Background: Pathologic changes in cortical gray matter (GM) and leptomeninges contribute to disability worsening in patients with multiple sclerosis (MS), but there is little evidence whether disease-modifying treatments can slow down cortical pathology in MS. Objectives: To investigate the effect of teriflunomide (TFM) and dimethyl fumarate (DMF) in reducing cortical pathology, as determined by percentage cortical volume change (PCVC) and leptomeningeal contrast enhancement (LMCE) on MRI. Methods: This was a retrospective, single-center, observational study that selected 60 TFM- and 60 DMF-treated MS patients over 24 months. Results: TFM had a lower rate of PCVC compared to DMF over 24 months (−0.2% vs. −2.94%, p = 0.004). Similar results were observed for percentage GM volume change over 0–12 (p = 0.044) and 0–24 (−0.44% vs. −3.12%, p = 0.015) months. No significant differences were found between the TFM and DMF groups in the frequency and number of LMCE foci over the follow-up. TFM showed a numerically lower rate of whole brain atrophy over 24 months (p = 0.077), compared to DMF. No significant clinical or MRI lesion differences between TFM and DMF were detected over follow-up. Conclusions: These findings suggest that TFM has a superior effect on the preservation of cortical GM volume, compared to DMF.
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Biomedicines | Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strat...

Biomedicines | Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strat... | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25 inhibits effector T cell activation, regulatory T cell expansion and survival, and activation-induced T-cell apoptosis. Because CD25 blockade reduces IL-2 consumption by effector T cells, it increases IL-2 bioavailability allowing for greater interaction with the intermediate-affinity IL-2R, and therefore drives the expansion of CD56bright natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56bright NK cell expansion and DAC HYP efficacy in reducing relapses and MRI evidence of disease activity in patients with RMS in phase II and phase III double-blind, placebo- and active comparator-controlled trials. Therapeutic efficacy was maintained during open-label extension studies. However, treatment was associated with an increased risk of rare adverse events, including cutaneous inflammation, autoimmune hepatitis, central nervous system Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) syndrome, and autoimmune Glial Fibrillary Acidic Protein (GFAP) alpha immunoglobulin-associated encephalitis. As a result, DAC HYP was removed from clinical use in 2018. The lingering importance of DAC is that its use led to a deeper understanding of the underappreciated role of innate immunity in the potential treatment of autoimmune disease. View Full-Text
Keywords: daclizumab; relapsing multiple sclerosis; CD25; innate immune system; interleukin-2; drug reaction with eosinophilia systemic symptoms; DRESS; autoimmunity
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Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014‐2017 - Bixler - - American Journal of Transplantation - Wiley Online Library

We evaluated clinical outcomes among organ recipients with donor‐derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014‐2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti‐HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti‐HCV and HCV RNA. Donor risk behaviors were abstracted from next‐of‐kin interviews and medical records. During 2014‐2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow‐up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow‐up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next‐of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease and death.
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Accuracy of Unenhanced MRI in the Detection of New Brain Lesions in Multiple Sclerosis | Radiology

Accuracy of Unenhanced MRI in the Detection of New Brain Lesions in Multiple Sclerosis | Radiology | Multiple sclerosis New Drugs Review | Scoop.it

Summary

At 3.0 T, use of a gadolinium-based contrast material at follow-up MRI did not change the diagnosis of interval disease progression in patients with multiple sclerosis.

 

Key Points

  • ■ In more than 500 follow-up images, only four of 1996 new or enlarged multiple sclerosis lesions would have been missed with 3.0-T MRI without the administration of contrast material.

  • ■ With 3.0-T MRI, the assessment of interval progression did not differ between contrast-enhanced and nonenhanced images.

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“Silent progression” or should it be “We can do better” –

“Silent progression” or should it be “We can do better” – | Multiple sclerosis New Drugs Review | Scoop.it
Silent Progression in Disease Activity-Free Relapsing Multiple Sclerosis.UCSF MS-EPIC Team, Cree BAC, Hollenbach JA, Bove R, Kirkish G, Sacco S, Caverzasi E, Bischof A, Gundel T, Zhu AH, Papi…...
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MRI-Monitoring-MS

MRI-Monitoring-MS | Multiple sclerosis New Drugs Review | Scoop.it
RSNA News Non-Contrast MRI is Effective in Monitoring MS Patients Findings support the possibility that contrast can be omitted from routine follow-up scans. March 12, 2019 Caption Brain MRI without contrast agent is just as effective as the contrast-enhanced approach for monitoring disease progression in patients with multiple sclerosis (MS), according to a new study in Radiology.    MRI with the administration of gadolinium-based contrast material is widely considered obligatory for follow-up scans of patients with MS. Gadolinium enhances the images and helps provide important diagnostic information, but it leads to both prolonged scan times and increased costs. There is also evidence that some of the metal remains in the body after contrast administration, although the long-term clinical impact of these deposits is unclear.    “These factors warrant evaluation of strategies for reducing or omitting contrast agent, especially in MS patients who often accumulate a high number of MRI scans over their lifetimes,” said study senior author Benedikt Wiestler, MD, from the Technische Universität München in Munich, Germany.   Advances in non-contrast MRI image acquisition and post-processing technology, along with the increasing availability of 3T MRI machines, have raised the possibility that non-enhanced scans could have a role in MS follow-up imaging. Study Demonstrates Potential of 3T MRI for MS Evaluation  Dr. Wiestler and colleagues used MRI to assess new or enlarged lesions in 359 patients with MS. Of 507 follow-up scans, 264 showed interval progression, defined as the presence of at least one new or unequivocally enlarged lesion on follow-up MRI scans. There were a total of 1,992 new or enlarged lesions. With 3T MRI, the assessment of interval progression did not differ significantly between the contrast-enhanced and non-enhanced images.  Axial MR images obtained in 32-year-old woman with relapsing-remitting multiple sclerosis. Images were obtained with subtraction of unenhanced T1-weighted MR image from contrast-enhanced MR image (T1sub), fluid-attenuated inversion recovery (FLAIR), and double inversion recovery (DIR). The new lesion (arrow), a small, subcortical lesion in right parietal lobe, is seen only on contrast-enhanced image; it was overlooked on DIR and FLAIR images. Note that there are several other new or enlarged lesions that can be seen on nonenhanced images. “In over 500 follow-up scans, we missed only four of 1,992 new or enlarged lesions,” Dr. Wiestler said. “Importantly, we did not miss disease activity in the non-enhanced scans in a single follow-up scan.”   Dr. Wiestler credited an image subtraction pipeline developed and researched at his facility for the powerful sensitivity of the non-contrast MRI in detecting newly occurring lesions. The approach combines 3D MRI and subtraction techniques, substantially improving visualization of new or enlarging white matter lesions.   This combination of 3D sequences and subtraction techniques is key to improving sensitivity for detecting newly occurred lesions, Dr. Wiestler said.   “Several vendors have made tools for generating subtraction images commercially available,” he said. “Implementing such tools into the routine clinical work flow will help to make the use of contrast agent dispensable in routine follow-up imaging of MS patients.”   Access the Radiology study, “Accuracy of Unenhanced MRI in the Detection of New Brain Lesions in Multiple Sclerosis,” at pubs.radiology.org.    Editor's Picks The Future of Thoracic Radiology Oscillating Microbubbles Could Revolutionize Ultrasound Iron Measurements with MRI Reveal Stroke’s Impact on Brain Non-Contrast MRI is Effective in Monitoring MS Patients News in Brief Annual Meeting Education and funding Journal highlights Member updates R&E Foundation Radiology in public focus
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