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E J Ramos González, L J Ramirez Jirano, D Z García Martínez, G G Ortiz, L F Jave Suárez, C A Leal Cortes, O K Bitzer Quintero
INTRODUCTION: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA)...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for Relapsing-Remitting Multiple Sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. Aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months...
March 10, 2018: Current Medical Research and Opinion
Raed Alroughani, Alexey Boyko
BACKGROUND: Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS. METHODS: The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice...
March 9, 2018: BMC Neurology
E D'Amico, F Patti, A Zanghì, S Lo Fermo, C G Chisari, M Zappia
BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e...
March 9, 2018: Expert Review of Clinical Pharmacology
Magnhild Sandberg-Wollheim, Orit Neudorfer, Augusto Grinspan, Bianca Weinstock-Guttman, Judith Haas, Guillermo Izquierdo, Claire Riley, Amy Perrin Ross, Peleg Baruch, Talya Drillman, Patricia K Coyle
Background: Appropriate counseling and treatment for women with multiple sclerosis (MS) who may become pregnant requires an understanding of the effects of exposure to disease-modifying therapies (DMTs) during pregnancy. Current reports and studies are limited in their usefulness, mostly by small sample size. Branded glatiramer acetate (GA) is a DMT approved for the treatment of relapsing forms of MS. For more than 2 decades, it has been shown to be efficacious and to have a favorable safety profile...
January 2018: International Journal of MS Care
Miguel Angel Ortiz, Laura Espino-Paisan, Concepcion Nunez, Roberto Alvarez-Lafuente, Elena Urcelay
In the 1990s, the betainterferons and glatiramer acetate were introduced for treating relapsing-remitting multiple sclerosis. These medications have a demonstrated record of efficacy and safety, although they require frequent administration via injection and are only partially effective. The optimization of treatment in patients who do not respond adequately to this first-line therapy is essential for attaining the best long-term outcomes. Switching to the recently approved emergent therapies is a strategy to consider for treatment of patients with a suboptimal response...
February 25, 2018: Current Medicinal Chemistry
Jacqueline Nicholas, Aaron Boster, Ning Wu, Wei-Shi Yeh, Monica Fay, Jon Kendter, Ming-Yi Huang, Andrew Lee
BACKGROUND: Data on comparative healthcare resource utilization and costs associated with the newer oral disease-modifying therapies (DMTs) for managing relapsing-remitting multiple sclerosis (MS) in routine clinical practice are limited. The purpose of this study was to estimate healthcare resource utilization, costs, and relapse rates in the year after initiating treatment with dimethyl fumarate (DMF), interferon (IFN)-β, glatiramer acetate (GA), teriflunomide, or fingolimod in routine clinical practice for patients with MS who did not receive a DMT in the previous year...
March 2018: PharmacoEconomics open
Thomas Prod'homme, Scott S Zamvil
Glatiramer acetate (GA) is a synthetic amino acid copolymer that is approved for treatment of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). GA reduces multiple sclerosis (MS) disease activity and has shown comparable efficacy with high-dose interferon-β. The mechanism of action (MOA) of GA has long been an enigma. Originally, it was recognized that GA treatment promoted expansion of GA-reactive T-helper 2 and regulatory T cells, and induced the release of neurotrophic factors...
February 12, 2018: Cold Spring Harbor Perspectives in Medicine
Raya Eilam, Menahem Segal, Rafael Malach, Michael Sela, Ruth Arnon, Rina Aharoni
To elucidate mechanisms contributing to cortical pathology in multiple sclerosis (MS), we investigated neurovascular aberrations, in particular the association of astrocytes with cortical neurons and blood vessels, in mice induced with experimental autoimmune encephalomyelitis (EAE). Blood-brain barrier (BBB) dysfunction was evident by leakage of the tracer sodium fluorescein, along with reduced expression of claudin-5 by endothelial cells and desmin by pericytes. Immunohistological and ultrastructural analyses revealed detachment of the astroglial cell bodies from the blood vessels and loss of their connections with both the blood vessels and the neuronal synapses...
February 9, 2018: Glia
Claudio Solaro, Giulia Gamberini, Fabio Giuseppe Masuccio
Depressive disorders are common in patients with multiple sclerosis, influencing their quality of life and adherence to treatments, as well as becoming more frequent with the progression of the disease and in the secondary progressive form of multiple sclerosis. Patients with multiple sclerosis often experience a typical cluster of symptoms in association with depression, such as fatigue, pain and cognitive impairment. However, the pathogenesis of multiple sclerosis-related depression remains partially unclear, even though genetic, immune-inflammatory and psychosocial factors might be seen to play a role, in addition to the brain structural alterations documented by magnetic resonance imaging studies...
February 7, 2018: CNS Drugs
Seiichi Omura, Fumitaka Sato, Nicholas E Martinez, Tierra Range, Lesya Ekshyyan, Alireza Minagar, J Steven Alexander, Ikuo Tsunoda
While most disease-modifying drugs (DMDs) regulate multiple sclerosis (MS) by suppressing inflammation, they can potentially suppress antiviral immunity, causing progressive multifocal leukoencephalopathy (PML). The DMD glatiramer acetate (GA) has been used for MS patients who are at high risk of PML. We investigated whether GA is safe for use in viral infections by using a model of MS induced by infection with Theiler's murine encephalomyelitis virus (TMEV). Treatment of TMEV-infected mice with GA neither enhanced viral loads nor suppressed antiviral immune responses, while it resulted in an increase in the Foxp3/Il17a ratio and IL-4/IL-10 production...
January 23, 2018: Archives of Virology
X Armoiry, A Kan, G J Melendez-Torres, R Court, P Sutcliffe, P Auguste, J Madan, C Counsell, A Clarke
BACKGROUND: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. METHODS: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA...
January 22, 2018: Journal of Neurology
O Fernández, M Delvecchio, G Edan, S Fredrikson, G Giovannoni, H-P Hartung, E Havrdova, L Kappos, C Pozzilli, P S Soerensen, B Tackenberg, P Vermersch, G Comi
BACKGROUND AND PURPOSE: The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. METHODS: A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe...
January 21, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Ülkü Türk Börü, Cansu Köseoğlu Toksoy, Cem Bölük, Adnan Bilgiç, Mustafa Taşdemir
Objectives We aimed to determine whether multiple sclerosis (MS) and methylprednisolone and disease-modifying drugs have an effect on menopausal age. Methods A total of 86 patients and 98 healthy subjects were included in this study. The natural menopausal age of the patients and healthy subjects were compared. The cumulative dosages of methylprednisolone, beta interferons (IFNβs), and glatiramer acetate were calculated. The effects of the Expanded Disability Status Scale (EDSS), duration of the disease, and cumulative dosage of medications on menopausal age were evaluated...
January 1, 2018: Journal of International Medical Research
Yael Hacohen, Yu Yi Wong, Christian Lechner, Maciej Jurynczyk, Sukhvir Wright, Bahadir Konuskan, Judith Kalser, Anne Lise Poulat, Helene Maurey, Esther Ganelin-Cohen, Evangeline Wassmer, Chery Hemingway, Rob Forsyth, Eva Maria Hennes, M Isabel Leite, Olga Ciccarelli, Banu Anlar, Rogier Hintzen, Romain Marignier, Jacqueline Palace, Matthias Baumann, Kevin Rostásy, Rinze Neuteboom, Kumaran Deiva, Ming Lim
Importance: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated. Objective: To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease. Design, Setting, and Participants: This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016...
January 5, 2018: JAMA Neurology
Maria Pia Amato, Antonio Bertolotto, Roberto Brunelli, Paola Cavalla, Benedetta Goretti, Maria Giovanna Marrosu, Francesco Patti, Carlo Pozzilli, Leandro Provinciali, Nicola Rizzo, Nicola Strobelt, Gioacchino Tedeschi, Maria Trojano, Giancarlo Comi
The original version contained a mistake. The authors have specified only in a few paragraphs that all the contents of the paper are meant for Copaxone but not for unbranded glatiramer acetate, Authors ask to add the specification of Copaxone or branded glatiramer acetate everytime.
February 2018: Neurological Sciences
G Borchard, D J A Crommelin
This review discusses the challenges to characterize and evaluate the peptide based drug glatiramer acetate (GA) and its follow-on products used for treatment of multiple sclerosis patients. Areas covered: GA is a highly complex mixture of peptides consisting of four amino acids. The various (physico)-chemical approaches and bioassays used for characterizing this complex drug product are described. It is not possible to link data from preclinical performance to outcomes observed in clinical trials as no critical attributes suitable for predicting the clinical performance in MS patients have been identified yet...
December 22, 2017: Expert Opinion on Drug Delivery
H K Olberg, G E Eide, R J Cox, Å Jul-Larsen, S L Lartey, C A Vedeler, K-M Myhr
BACKGROUND AND PURPOSE: We have previously shown that patients with multiple sclerosis receiving immunomodulatory treatment have reduced seroprotection rates after influenza immunization. The aim of this study was to further investigate the influence of immunomodulatory therapies on the antibody response and seroprotection rates in patients immunized with seasonal influenza vaccine in 2012/2013 compared with healthy controls. METHODS: Ninety patients receiving fingolimod, glatiramer acetate, interferon beta-1a/1b, natalizumab or no therapy were compared with 62 healthy controls...
March 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
María Laura Palumbo, María Emilia Di Rosso, Elias Hugo Simon, María Rosa Gonzalez Murano, Ana María Genaro
It is known that long-term exposure to stressful situations can produce severe consequences affecting behavioral, endocrine and immunological parameters. We have previously shown that stressed BALB/c mice had poor learning performance, which was reverted by glatiramer acetate treatment through a mechanism that likely involved the regulation of the cytokine balance and adult neurogenesis. In addition, recent results suggest that cytokine and neurotrophin expression in the hippocampus displayed similar tendencies as those in the serum...
November 23, 2017: Cytokine
Iris Grossman, Sarah Kolitz, Arthur Komlosh, Benjamin Zeskind, Vera Weinstein, Daphna Laifenfeld, Adrian Gilbert, Oren Bar-Ilan, Kevin D Fowler, Tal Hasson, Attila Konya, Kevin Wells-Knecht, Pippa Loupe, Sigal Melamed-Gal, Tatiana Molotsky, Revital Krispin, Galia Papir, Yousif Sahly, Michael R Hayden
Copaxone (glatiramer acetate, GA), a structurally and compositionally complex polypeptide nonbiological drug, is an effective treatment for multiple sclerosis, with a well-established favorable safety profile. The short antigenic polypeptide sequences comprising therapeutically active epitopes in GA cannot be deciphered with state-of-the-art methods; and GA has no measurable pharmacokinetic profile and no validated pharmacodynamic markers. The study reported herein describes the use of orthogonal standard and high-resolution physicochemical and biological tests to characterize GA and a U...
November 2017: Annals of the New York Academy of Sciences
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