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multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#1
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533365/prediction-of-disease-activity-in-models-of-multiple-sclerosis-by-molecular-magnetic-resonance-imaging-of-p-selectin
#2
Antoine Philippe Fournier, Aurélien Quenault, Sara Martinez de Lizarrondo, Maxime Gauberti, Gilles Defer, Denis Vivien, Fabian Docagne, Richard Macrez
New strategies for detecting disease activity in multiple sclerosis are being investigated to ameliorate diagnosis and follow-up of patients. Today, although magnetic resonance imaging (MRI) is widely used to diagnose and monitor multiple sclerosis, no imaging tools exist to predict the evolution of disease and the efficacy of therapeutic strategies. Here, we show that molecular MRI targeting the endothelial adhesion molecule P-selectin unmasks the pathological events that take place in the spinal cord of mice subjected to chronic or relapsing experimental autoimmune encephalomyelitis...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28529497/efficacy-and-safety-of-fingolimod-in-daily-practice-experience-of-an-academic-ms-french-center
#3
Thomas Roux, Elisabeth Maillart, Jean-Sébastien Vidal, Sophie Tezenas du Montcel, Catherine Lubetzki, Caroline Papeix
INTRODUCTION: Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, decreases the annual relapse rate (ARR) in relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to assess the efficacy and safety of Fg in daily practice in patients with RRMS, previously treated with natalizumab (Nz) or not, and systematically followed during at least 1 year. METHODS: Data were collected from the patient files. Primary endpoint was the comparison between the ARR the year before Fg onset and after 1 and 2 years of Fg treatment...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28528567/cognitive-behavioral-therapy-positively-affects-fatigue-in-patients-with-multiple-sclerosis-results-of-a-randomized-controlled-trial
#4
Lizanne E van den Akker, Heleen Beckerman, Emma H Collette, Jos Wr Twisk, Gijs Bleijenberg, Joost Dekker, Hans Knoop, Vincent de Groot
BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive. OBJECTIVE: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation. METHODS: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28528566/does-aerobic-training-alleviate-fatigue-and-improve-societal-participation-in-patients-with-multiple-sclerosis-a-randomized-controlled-trial
#5
Martin Heine, Olaf Verschuren, Erwin Lj Hoogervorst, Erik van Munster, Hub Ga Hacking, Anne Visser-Meily, Jos Wr Twisk, Heleen Beckerman, Vincent de Groot, Gert Kwakkel
BACKGROUND: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. OBJECTIVE: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. METHODS: Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28528469/multiple-sclerosis-treatment-with-fingolimod-profile-of-non-cardiologic-adverse-events
#6
REVIEW
Yara Dadalti Fragoso
Fingolimod was the first oral medication approved for management of multiple sclerosis and is currently used by tens of thousands patients worldwide. Fingolimod acts via the sphingosine 1-phosphate (S1P) receptor, maintaining peripheral lymphocytes entrapped in the lymph nodes. In consequence, there is a reduction in the infiltration of aggressive lymphocytes into the central nervous system. The drug is safe and effective, and its first hours of use are associated with related to S1P receptors in the heart...
May 20, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28527045/amyotrophic-lateral-sclerosis-like-superoxide-dismutase-1-proteinopathy-is-associated-with-neuronal-loss-in-parkinson-s-disease-brain
#7
Benjamin G Trist, Katherine M Davies, Veronica Cottam, Sian Genoud, Richard Ortega, Stéphane Roudeau, Asuncion Carmona, Kasun De Silva, Valerie Wasinger, Simon J G Lewis, Perminder Sachdev, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Helen J Ball, Glenda M Halliday, Dominic J Hare, Kay L Double
Neuronal loss in numerous neurodegenerative disorders has been linked to protein aggregation and oxidative stress. Emerging data regarding overlapping proteinopathy in traditionally distinct neurodegenerative diseases suggest that disease-modifying treatments targeting these pathological features may exhibit efficacy across multiple disorders. Here, we describe proteinopathy distinct from classic synucleinopathy, predominantly comprised of the anti-oxidant enzyme superoxide dismutase-1 (SOD1), in the Parkinson's disease brain...
May 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28524150/-functional-examinations-of-visual-channels-clinical-aspects
#8
M V Zueva, I V Tsapenko, E P Lantukh, N M Maglakelidze
The review discusses literature data on the clinical relevance of functional assessment of magno- (M), parvo- (P), and koniocellular (K) pathways. It also covers the differential contribution of the M, P, and K channels to visual impairments and how it determines the prognosis, early diagnosis, and treatment choice in patients with neurodegenerative diseases of the retina and brain. Selective changes in the performance of the visual channels are investigated by the example of glaucoma and optic neuritis in multiple sclerosis (MS) patients...
2017: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/28523586/ocrelizumab-first-global-approval
#9
James E Frampton
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS...
June 2017: Drugs
https://www.readbyqxmd.com/read/28516804/spinal-cord-atrophy-as-a-primary-outcome-measure-in-phase-ii-trials-of-progressive-multiple-sclerosis
#10
Niamh Cawley, Carmen Tur, Ferran Prados, Domenico Plantone, Hugh Kearney, Khaled Abdel-Aziz, Sebastian Ourselin, Claudia Am Gandini Wheeler-Kingshott, David H Miller, Alan J Thompson, Olga Ciccarelli
OBJECTIVES: To measure the development of spinal cord (SC) atrophy over 1 year in patients with progressive multiple sclerosis (PMS) and determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA) as an outcome measure in clinical trials. METHODS: In total, 44 PMS patients (26 primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12 months...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28516332/prevalence-and-mortality-of-patients-with-multiple-sclerosis-in-france-in-2012-a-study-based-on-french-health-insurance-data
#11
Stéphanie Foulon, Géric Maura, Marie Dalichampt, François Alla, Marc Debouverie, Thibault Moreau, Alain Weill
Data on the prevalence of multiple sclerosis (MS) in France are scarce. National and regional updated estimates are needed to better plan health policies. In this nationwide study, we provided estimates of the prevalence of MS in France in 2012 and mortality rate in 2013. MS cases were identified in the French national health insurance database (SNIIRAM-PMSI) using reimbursement data for disease-modifying treatment, long-term disease status for MS, disability pension for MS, and hospitalisation for MS (MS ICD-10 code: G35)...
May 17, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28516256/-skin-diseases-associated-with-environmental-factors
#12
REVIEW
Vera Mahler
BACKGROUND: Multiple environmental exposures may derange the regulatory and repair mechanisms of the skin and lead to dermatological disease. OBJECTIVES: Provide an overview of non-allergic skin diseases associated with environmental factors. MATERIALS AND METHODS: Review of current scientific evidence for associations of non-allergic skin diseases with environmental exposures: irritation, chemicals, infection, UV-radiation, temperature. RESULTS: Predisposition (constitution e...
May 17, 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28515158/the-anti-psoriatic-drug-monomethylfumarate-increases-nuclear-factor-erythroid-2-related-factor-2-nrf2-levels-and-induces-aquaporin-3-aqp3-mrna-and-protein-expression
#13
Inas Helwa, Vivek Choudhary, Xunsheng Chen, Ismail Kaddour-Djebbar, Wendy B Bollag
BACKGROUND: Oxidative stress contributes to inflammatory skin diseases including psoriasis. Monomethylfumarate (MMF) is an anti-psoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular anti-oxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. OBJECTIVE: We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28514773/a-feasibility-study-of-the-full-outpatient-conduction-of-hematopoietic-transplants-in-persons-with-multiple-sclerosis-employing-autologous-non-cryopreserved-peripheral-blood-stem-cells
#14
Guillermo J Ruiz-Argüelles, Andrés A León-Peña, Mónica León-González, Ana Karen Nuñez-Cortes, Juan Carlos Olivares-Gazca, Iván Murrieta-Alvarez, Jocelyn Vargas-Espinosa, Emilio Medina-Ceballos, Yahveth Cantero-Fortiz, Alejandro Ruiz-Argüelles, Manuel A Ruiz-Delgado, Rodrigo J Ruiz-Delgado, Guillermo Ruiz-Reyes, Manuel Priesca-Marín, Merari Starlight Torres-Priego, David Blumenkron-Marroquin, Guillermo J Ruiz-Delgado
BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217...
May 18, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28512753/serum-neurofilament-light-a-biomarker-of-neuronal-damage-in-multiple-sclerosis
#15
Giulio Disanto, Christian Barro, Pascal Benkert, Yvonne Naegelin, Sabine Schädelin, Antonella Giardiello, Chiara Zecca, Kaj Blennow, Henrik Zetterberg, David Leppert, Ludwig Kappos, Claudio Gobbi, Jens Kuhle
OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the CSF and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in MS. METHODS: sNfL levels were measured in healthy controls (HC, n=254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n=142); (2) longitudinal with repeated serum sampling (n=246, median (IQR) follow-up 3...
May 16, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#16
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28511812/acute-management-of-symptomatic-subependymal-giant-cell-astrocytoma-with-everolimus
#17
Monica S Arroyo, Darcy A Krueger, Eileen Broomall, Charles B Stevenson, David N Franz
BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors, which can cause obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC). These tumors require routine surveillance with magnetic resonance imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs with an mechanistic target of rapamycin (mTOR) inhibitor because these medications have demonstrated efficacy and safety in multiple prospective clinical trials. For symptomatic SEGAs, standard therapy typically involves surgical resection of the tumor to relieve mass effect and resolve hydrocephalus...
April 18, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28511703/mindfulness-based-stress-reduction-for-people-with-multiple-sclerosis-a-feasibility-randomised-controlled-trial
#18
Robert Simpson, Frances S Mair, Stewart W Mercer
BACKGROUND: Multiple sclerosis (MS) is a stressful condition. Mental health comorbidity is common. Stress can increase the risk of depression, reduce quality of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based Stress Reduction (MBSR) may help, but has been little studied in MS, particularly among more disabled individuals. METHODS: The objective of this study was to test the feasibility and likely effectiveness of a standard MBSR course for people with MS...
May 16, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28511578/retinal-atrophy-in-relation-to-visual-functioning-and-vision-related-quality-of-life-in-patients-with-multiple-sclerosis
#19
Lisanne J Balk, Danko Coric, Jenny A Nij Bijvank, Joep Killestein, Bernard Mj Uitdehaag, Axel Petzold
BACKGROUND: Inner retinal layer atrophy in patients with multiple sclerosis (MS) has been validated as a structural imaging biomarker for neurodegeneration. OBJECTIVE: To determine how retinal layer thickness relates to high-contrast visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related quality of life (QoL) and to investigate the effect of previous episodes on MS-associated optic neuritis (MSON). METHODS: Spectral-domain optical coherence tomography (SD-OCT) was performed in 267 patients with MS...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28511151/peripheral-arteriovenous-fistula-as-vascular-access-for-long-term-chemotherapy
#20
Oleksiy O Kovalyov, Oleksandr G Kostyuk, Tetyana V Tkachuk
INTRODUCTION: To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
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