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https://www.readbyqxmd.com/read/29142299/the-immunomodulatory-drug-glatiramer-acetate-is-also-an-effective-antimicrobial-agent-that-kills-gram-negative-bacteria
#1
Stig Hill Christiansen, Ronan A Murphy, Kristian Juul-Madsen, Marlene Fredborg, Michael Lykke Hvam, Esben Axelgaard, Sandra M Skovdal, Rikke Louise Meyer, Uffe B Skov Sørensen, Arne Möller, Jens Randel Nyengaard, Niels Nørskov-Lauritsen, Mikala Wang, Mihaela Gadjeva, Kenneth A Howard, Jane C Davies, Eskild Petersen, Thomas Vorup-Jensen
Classic drug development strategies have failed to meet the urgent clinical needs in treating infections with Gram-negative bacteria. Repurposing drugs can lead to timely availability of new antibiotics, accelerated by existing safety profiles. Glatiramer acetate (GA) is a widely used and safe formulation for treatment of multiple sclerosis. It contains a large diversity of essentially isomeric polypeptides with the cationic and amphiphilic character of many antimicrobial peptides (AMP). Here, we report that GA is antibacterial, targeting Gram-negative organisms with higher activity towards Pseudomonas aeruginosa than the naturally-occurring AMP LL-37 in human plasma...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141831/long-term-follow-up-of-a-randomized-study-of-combination-interferon-and-glatiramer-acetate-in-multiple-sclerosis-efficacy-and-safety-results-up-to-7-years
#2
Fred D Lublin, Stacey S Cofield, Gary R Cutter, Tarah Gustafson, Stephen Krieger, Ponnada A Narayana, Flavia Nelson, Amber R Salter, Jerry S Wolinsky
BACKGROUND: To report the long-term results of the blinded extension phase of the randomized, controlled study of the combined use of interferon beta-1a (IFN) 30μg IM weekly and glatiramer acetate (GA) 20mg daily compared to each agent alone in relapsing-remitting multiple sclerosis (RRMS). METHODS: 1008 RRMS patients were followed on protocol until the last participant enrolled completed 3 years, allowing some subjects to be followed for up to 7 years. The primary endpoint was reduction in annualized relapse rate...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141809/treatment-satisfaction-across-injectable-infusion-and-oral-disease-modifying-therapies-for-multiple-sclerosis
#3
Tessa Eagle, Fiona Stuart, Alicia S Chua, Allison LaRussa, Kaitlynne Leclaire, Sandra L Cook, Tanuja Chitnis, Howard L Weiner, Bonnie I Glanz, Brian C Healy
BACKGROUND: The recent approval of oral disease-modifying therapies (DMTs) for multiple sclerosis (MS) has provided patients with a new route of therapy administration. Little research has compared patients' experiences with and perceptions of injectable, infusion and oral MS therapies. METHODS: Three hundred fifty-seven treated MS patients enrolled in the CLIMB study completed the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM provides information regarding perceived effectiveness, side effects, convenience and overall satisfaction...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141791/comparing-the-efficacy-of-disease-modifying-therapies-in-multiple-sclerosis
#4
REVIEW
Dimos D Mitsikostas, Douglas S Goodin
Establishing the relative efficacy and safety of the different disease modifying therapies (DMTs) in multiple sclerosis (MS) is critical to the choice of agent that clinicians recommend for individual MS patients. The best evidence for the relative efficacy of the different DMTs comes from head-to-head randomized clinical trials (RCTs). Understanding that outcome-measures with the best established validity are the relapse rate and the actual (not the "confirmed") change in the extended disability status scale (EDSS), we conclude from these head-to-head RCTs that interferon-beta (IFNβ) given subcutaneously multiple times per week (either IFNβ-1b or IFNβ-1a) and glatiramer acetate (GA) are about equivalent in terms of efficacy and that both of these agents, as well as many of the other DMTs, are superior to weekly intramuscular IFNβ-1a...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29139001/the-assessment-for-disinvestment-of-intramuscular-interferon-beta-for-relapsing-remitting-multiple-sclerosis-in-brazil
#5
REVIEW
Livia Lovato Pires de Lemos, Augusto Afonso Guerra Júnior, Marisa Santos, Carlos Magliano, Isabela Diniz, Kathiaja Souza, Ramon Gonçalves Pereira, Juliana Alvares, Brian Godman, Marion Bennie, Ivan Ricardo Zimmermann, Vânia Crisitna Canuto Dos Santos, Clarice Alegre Pretramale, Francisco de Assis Acurcio
In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-β-1a-IM) was inferior to the other beta interferons (IFN-βs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-β-1a-IM in Brazil...
November 14, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/29120092/restoration-of-axon-conduction-and-motor-deficits-by-therapeutic-treatment-with-glatiramer-acetate
#6
Spencer Moore, Anna J Khalaj, Rhusheet Patel, JaeHee Yoon, Daniel Ichwan, Liat Hayardeny, Seema K Tiwari-Woodruff
No abstract text is available yet for this article.
January 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29116612/the-complement-system-as-a-biomarker-of-disease-activity-and-response-to-treatment-in-multiple-sclerosis
#7
REVIEW
Alexandru Tatomir, Anamaria Talpos-Caia, Freidrich Anselmo, Adam M Kruszewski, Dallas Boodhoo, Violeta Rus, Horea Rus
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability...
November 8, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29095108/pharmacogenetics-of-glatiramer-acetate-therapy-for-multiple-sclerosis-the-impact-of-genome-wide-association-studies-identified-disease-risk-loci
#8
Olga Kulakova, Vitalina Bashinskaya, Ivan Kiselev, Natalia Baulina, Ekaterina Tsareva, Ruslan Nikolaev, Maxim Kozin, Sergey Shchur, Alexander Favorov, Alexey Boyko, Olga Favorova
AIM: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. PATIENTS & METHODS: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. RESULTS: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f  = 0...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29093064/assessing-association-of-comorbidities-with-treatment-choice-and-persistence-in-ms-a-real-life-multicenter-study
#9
Alice Laroni, Alessio Signori, Giorgia T Maniscalco, Roberta Lanzillo, Cinzia Valeria Russo, Eleonora Binello, Salvatore Lo Fermo, Annamaria Repice, Pietro Annovazzi, Simona Bonavita, Marinella Clerico, Damiano Baroncini, Luca Prosperini, Sara La Gioia, Silvia Rossi, Eleonora Cocco, Jessica Frau, Valentina Torri Clerici, Elisabetta Signoriello, Arianna Sartori, Ignazio Roberto Zarbo, Sarah Rasia, Cinzia Cordioli, Raffaella Cerqua, Alessia Di Sapio, Luigi Lavorgna, Simona Pontecorvo, Caterina Barrilà, Francesco Saccà, Barbara Frigeni, Sabrina Esposito, Domenico Ippolito, Fabio Gallo, Maria Pia Sormani
OBJECTIVE: To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort. METHODS: We included newly diagnosed patients (2010-2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch...
November 1, 2017: Neurology
https://www.readbyqxmd.com/read/29090833/equivalence-and-regulatory-approaches-of-nonbiological-complex-drug-products-across-the-united-states-the-european-union-and-turkey
#10
REVIEW
Z Gulsen Oner, Sarah L J Michel, James E Polli
Regulatory agencies around the world may have different standards and approaches to evaluate and approve drug products and biological products. We describe the U.S. Food and Drug Administration's (FDA) Generic Drug User Fee Act program, as well as their approach to complex products. We discuss regulatory approaches for the development of nonbiological complex drug follow-ons and approval pathways in the United States. We compare FDA policies with other regulatory agencies (i.e., the European Medicines Agency and the Turkish Medicines and Medical Devices Agency)...
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29090021/liver-injury-and-glatiramer-acetate-an-uncommon-association-case-report-and-literature-review
#11
REVIEW
Javier Almeida, Nuria Solà-Valls, Elisa Pose, Yolanda Blanco, María Sepúlveda, Sara Llufriu, Pere Gines, Albert Saiz
We report the case of a 65-year-old woman who presented with a 1-month history of progressive paraparesia associated with a thoracic lesion with irregular ring-like gadolinium enhancement. Biopsy of the lesion confirmed the demyelinating origin and brain magnetic resonance imaging showed additional lesions demonstrative of dissemination in space. Immunomodulatory therapy with glatiramer acetate (GA) was started after having a second relapse 2 months later. Shortly after initiation, the patient developed acute hepatitis...
November 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29070967/case-report-glatiramer-acetate-induced-serum-sickness
#12
Paul Ferguson
Multiple sclerosis (MS) is a central nervous system demyelinating disease with a prevalence of approximately 400,000 individuals in the United States. Glatiramer acetate is a frequently prescribed disease-modifying therapy used for the management of relapsing forms of the disease. A 40-year-old woman with relapsing-remitting MS presented with symptomatic concerns of vomiting, fever, diffuse rash, joint and low back pain, and distal lower-limb paresthesia and was subsequently admitted to the hospital for investigation and treatment...
September 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/29050818/decreased-serum-levels-of-scd40l-and-il-31-correlate-in-treated-patients-with-relapsing-remitting-multiple-sclerosis
#13
José de J Guerrero-García, Argelia E Rojas-Mayorquín, Yeminia Valle, Jorge R Padilla-Gutiérrez, Víctor A Castañeda-Moreno, Mario A Mireles-Ramírez, José F Muñoz-Valle, Daniel Ortuño-Sahagún
The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS...
October 5, 2017: Immunobiology
https://www.readbyqxmd.com/read/28940162/infections-in-patients-receiving-multiple-sclerosis-disease-modifying-therapies
#14
REVIEW
Elena Grebenciucova, Amy Pruitt
PURPOSE OF REVIEW: This paper will systemically review the risk of infections associated with current disease-modifying treatments and will discuss pre-treatment testing recommendations, infection monitoring strategies, and patient education. RECENT FINDINGS: Aside from glatiramer acetate and interferon-beta therapies, all other multiple sclerosis treatments to various degrees impair immune surveillance and may predispose patients to the development of both community-acquired and opportunistic infections...
September 22, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28935954/process-signatures-in-glatiramer-acetate-synthesis-structural-and-functional-relationships
#15
Víctor R Campos-García, Daniel Herrera-Fernández, Carlos E Espinosa-de la Garza, German González, Luis Vallejo-Castillo, Sandra Avila, Leslie Muñoz-García, Emilio Medina-Rivero, Néstor O Pérez, Isabel Gracia-Mora, Sonia Mayra Pérez-Tapia, Rodolfo Salazar-Ceballos, Lenin Pavón, Luis F Flores-Ortiz
Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28914229/clinical-effectiveness-and-cost-effectiveness-of-beta-interferon-and-glatiramer-acetate-for-treating-multiple-sclerosis-systematic-review-and-economic-evaluation
#16
G J Melendez-Torres, Peter Auguste, Xavier Armoiry, Hendramoorthy Maheswaran, Rachel Court, Jason Madan, Alan Kan, Stephanie Lin, Carl Counsell, Jacoby Patterson, Jeremy Rodrigues, Olga Ciccarelli, Hannah Fraser, Aileen Clarke
BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#17
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
November 2017: Autoimmunity
https://www.readbyqxmd.com/read/28860067/a-novel-role-for-osteopontin-in-macrophage-mediated-amyloid-%C3%AE-clearance-in-alzheimer-s-models
#18
Altan Rentsendorj, Julia Sheyn, Dieu-Trang Fuchs, David Daley, Brenda C Salumbides, Hannah E Schubloom, Nadav J Hart, Songlin Li, Eric Y Hayden, David B Teplow, Keith L Black, Yosef Koronyo, Maya Koronyo-Hamaoui
Osteopontin (OPN), a matricellular immunomodulatory cytokine highly expressed by myelomonocytic cells, is known to regulate immune cell migration, communication, and response to brain injury. Enhanced cerebral recruitment of monocytes achieved through glatiramer acetate (GA) immunization or peripheral blood enrichment with bone marrow (BM)-derived CD115(+) monocytes (Mo(BM)) curbs amyloid β-protein (Aβ) neuropathology and preserves cognitive function in murine models of Alzheimer's disease (ADtg mice). To elucidate the beneficial mechanisms of these immunomodulatory approaches in AD, we focused on the potential role of OPN in macrophage-mediated Aβ clearance...
January 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28857632/adherence-persistence-and-discontinuation-among-hispanic-and-african-american-patients-with-multiple-sclerosis-treated-with-fingolimod-or-glatiramer-acetate
#19
Mitzi J Williams, Kristen Johnson, Helen M Trenz, Stephanie Korrer, Rachel Halpern, Yujin Park, Vivian Herrera
OBJECTIVE: Few studies have examined compliance to disease-modifying therapies (DMTs) for multiple sclerosis (MS) in minority populations. This study compared adherence, discontinuation, and persistence for fingolimod (FTY) and glatiramer acetate (GA) initiators among Hispanic and African American patients with MS. METHODS: This retrospective claims data study examined Hispanic and African American adults with MS who initiated FTY or GA between September 1, 2010 and June 30, 2014...
October 3, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28829817/genomic-correlates-of-glatiramer-acetate-adverse-cardiovascular-effects-lead-to-a-novel-locus-mediating-coronary-risk
#20
Ingrid Brænne, Lingyao Zeng, Christina Willenborg, Vinicius Tragante, Thorsten Kessler, Cristen J Willer, Markku Laakso, Lars Wallentin, Paul W Franks, Veikko Salomaa, Abbas Dehghan, Thomas Meitinger, Nilesh J Samani, Folkert W Asselbergs, Jeanette Erdmann, Heribert Schunkert
Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes...
2017: PloS One
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