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https://www.readbyqxmd.com/read/27785417/metabolic-response-to-glatiramer-acetate-therapy-in-multiple-sclerosis-patients
#1
Lidia De Riccardis, Alessandra Ferramosca, Antonio Danieli, Giorgio Trianni, Vincenzo Zara, Francesca De Robertis, Michele Maffia
Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4(+), the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27473139/mtr-recovery-in-brain-lesions-in-the-become-study-of-glatiramer-acetate-vs-interferon-%C3%AE-1b
#2
Robert A Brown, Sridar Narayanan, Nikola Stikov, Stuart Cook, Diego Cadavid, Leo Wolansky, Douglas L Arnold
OBJECTIVE: To compare magnetization transfer changes in new brain MRI lesions identified during monthly imaging in patients with multiple sclerosis (MS) randomized to treatment with 250 μg subcutaneous interferon-β-1b (IFN-β-1b) every other day or daily 20 mg glatiramer acetate (GA) in a post hoc study using data from the Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI (BECOME) trial. METHODS: T1-weighted images acquired with and without fat saturation pulses in the BECOME study were evaluated and found to exhibit magnetization transfer ratio (MTR) effects, and were used to compute MTR images (FSMTR)...
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/27411339/innate-phagocytosis-by-peripheral-blood-monocytes-is-altered-in-alzheimer-s-disease
#3
Ben J Gu, Xin Huang, Amber Ou, Alan Rembach, Christopher Fowler, Pavan K Avula, Adam Horton, James D Doecke, Victor L Villemagne, S Lance Macaulay, Paul Maruff, Erica L Fletcher, Robyn Guymer, James S Wiley, Colin L Masters
Sporadic Alzheimer's disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of clearance could underlie this process, and recent genetic association studies point towards involvement of the phagocytosis and autophagy pathways. We developed a real-time tri-color flow cytometry method to quantitate the phagocytic function of human peripheral blood monocyte subsets including non-classic CD14(dim)CD16(+), intermediate CD14(+)CD16(+) and classic CD14(+)CD16(-) monocytes...
September 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27404942/an-association-between-glatiramer-acetate-and-malignant-melanoma
#4
John Walker, AnneLiese Smylie, Michael Smylie
A 43-year-old female receiving immunomodulatory therapy with glatiramer acetate (copaxone, GA) for relapsing, remitting multiple sclerosis was diagnosed with stage IIIB melanoma that recurred <7 months after resection and lymphadenectomy. In preparation for systemic therapy the patient discontinued GA, and shortly thereafter experienced spontaneous and complete clinical and radiographic resolution of her disease. The development and subsequent regression of melanoma in this patient may be due to the use and subsequent discontinuation of GA, and our discussion of the case includes the potential immunologic mechanisms that may provide an explanation for our findings...
September 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27277705/survey-of-us-patients-with-multiple-sclerosis-comparison-of-the-new-electronic-interferon-beta-1b-autoinjector-betaconnect%C3%A2-with-mechanical-autoinjectors
#5
Donald A Barone, Barry A Singer, Lubo Merkov, Mark Rametta, Gustavo Suarez
INTRODUCTION: Patients with multiple sclerosis (MS) generally undergo long-term treatment with disease-modifying therapies (DMTs). In the US, patients taking glatiramer acetate, interferon beta-1a, or interferon beta-1b, typically use a mechanical autoinjector. Recent survey results have shown that using an electronic autoinjector, such as BETACONNECT™ (Bayer Pharma AG) for interferon beta-1b/Betaseron(®) (Bayer Pharma AG) may reduce injection discomfort and increase patient satisfaction with treatment...
December 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27131971/autoantigen-specific-immunosuppression-with-tolerogenic-peripheral-blood-cells-prevents-relapses-in-a-mouse-model-of-relapsing-remitting-multiple-sclerosis
#6
Christian Kleist, Elisabeth Mohr, Sadanand Gaikwad, Laura Dittmar, Stefanie Kuerten, Michael Platten, Walter Mier, Michael Schmitt, Gerhard Opelz, Peter Terness
BACKGROUND: Dendritic cells (DCs) rendered suppressive by treatment with mitomycin C and loaded with the autoantigen myelin basic protein demonstrated earlier their ability to prevent experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis (MS). This provides an approach for prophylactic vaccination against autoimmune diseases. For clinical application such DCs are difficult to generate and autoantigens hold the risk of exacerbating the disease. METHODS: We replaced DCs by peripheral mononuclear cells and myelin autoantigens by glatiramer acetate (Copaxone(®)), a drug approved for the treatment of MS...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27035896/update-on-monitoring-and-adverse-effects-of-first-generation-disease-modifying-therapies-and-their-recently-approved-versions-in-relapsing-forms-of-multiple-sclerosis
#7
Divyanshu Dubey, Christopher A Cano, Olaf Stüve
PURPOSE OF REVIEW: As of April 2015, 13 disease modifying therapies (DMTs) have been approved by the Food and Drug Administration. The older agents continue to be utilized across the globe, especially in developing countries where many newer DMTs are still not available. Even though first generation DMTs have modest efficacy they have long term safety profile, and are considered safer than the second generation DMTs. RECENT FINDINGS: A PEGylated interferon beta-1a preparation that is administered subcutaneously every 2 weeks was also recently approved...
June 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/26711576/functional-effects-of-the-antigen-glatiramer-acetate-are-complex-and-tightly-associated-with-its-composition
#8
Tal Hasson, Sarah Kolitz, Fadi Towfic, Daphna Laifenfeld, Shlomo Bakshi, Olga Beriozkin, Maya Shacham-Abramson, Bracha Timan, Kevin D Fowler, Tal Birnberg, Attila Konya, Arthur Komlosh, David Ladkani, Michael R Hayden, Benjamin Zeskind, Iris Grossman
Glatiramer acetate (Copaxone®; GA) is a non-biological complex drug for multiple sclerosis. GA modulated thousands of genes in genome-wide expression studies conducted in THP-1 cells and mouse splenocytes. Comparing GA with differently-manufactured glatiramoid Polimunol (Synthon) in mice yielded hundreds of differentially expressed probesets, including biologically-relevant genes (e.g. Il18, adj p<9e-6) and pathways. In human monocytes, 700+ probesets differed between Polimunol and GA, enriching for 130+ pathways including response to lipopolysaccharide (adj...
January 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/26601118/glatiramer-acetate-treatment-negatively-regulates-type-i-interferon-signaling
#9
Nicolas Molnarfi, Thomas Prod'homme, Ulf Schulze-Topphoff, Collin M Spencer, Martin S Weber, Juan C Patarroyo, Patrice H Lalive, Scott S Zamvil
OBJECTIVE: Glatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization. METHODS: Monocytes were isolated from myeloid differentiation primary response gene 88 (MyD88)-deficient, Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN)-β (TRIF)-deficient, IFN-α/β receptor subunit 1 (IFNAR1)-deficient, and wild-type (WT) mice and human peripheral blood...
December 2015: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/26473741/equivalent-gene-expression-profiles-between-glatopa%C3%A2-and-copaxone%C3%A2
#10
COMPARATIVE STUDY
Josephine S D'Alessandro, Jay Duffner, Joel Pradines, Ishan Capila, Kevin Garofalo, Ganesh Kaundinya, Benjamin M Greenberg, Daniel Kantor, Tanmoy C Ganguly
Glatopa™ is a generic glatiramer acetate recently approved for the treatment of patients with relapsing forms of multiple sclerosis. Gene expression profiling was performed as a means to evaluate equivalence of Glatopa and Copaxone®. Microarray analysis containing 39,429 unique probes across the entire genome was performed in murine glatiramer acetate--responsive Th2-polarized T cells, a test system highly relevant to the biology of glatiramer acetate. A closely related but nonequivalent glatiramoid molecule was used as a control to establish assay sensitivity...
2015: PloS One
https://www.readbyqxmd.com/read/26458562/modern-analytics-for-synthetically-derived-complex-drug-substances-nmr-afff-mals-and-ms-tests-for-glatiramer-acetate
#11
Sarah Rogstad, Eric Pang, Cynthia Sommers, Meng Hu, Xiaohui Jiang, David A Keire, Michael T Boyne
Glatiramer acetate (GA) is a mixture of synthetic copolymers consisting of four amino acids (glutamic acid, lysine, alanine, and tyrosine) with a labeled molecular weight range of 5000 to 9000 Da. GA is marketed as Copaxone™ by Teva for the treatment of multiple sclerosis. Here, the agency has evaluated the structure and composition of GA and a commercially available comparator, Copolymer-1. Modern analytical technologies which can characterize these complex mixtures are desirable for analysis of their comparability and structural "sameness...
November 2015: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/26458034/equivalence-of-generic-glatiramer-acetate-in-multiple-sclerosis-a-randomized-clinical-trial
#12
RANDOMIZED CONTROLLED TRIAL
Jeffrey Cohen, Anna Belova, Krzysztof Selmaj, Christian Wolf, Maria Pia Sormani, Janine Oberyé, Evelyn van den Tweel, Roel Mulder, Norbert Koper, Gerrit Voortman, Frederik Barkhof
IMPORTANCE: The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives. OBJECTIVE: To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability...
December 2015: JAMA Neurology
https://www.readbyqxmd.com/read/26356401/-release-active-antibodies-to-s100-protein-are-able-to-improve-the-experimental-allergic-encephalomyelitis
#13
K K Ganina, Yu L Dugina, E S Zhavbert, I A Ertuzun, O I Epstein, I N Abdurasulova
AIM: To reveal the effects of release-active antibodies to S100 protein in an animal model of multiple sclerosis. MATERIAL AND METHODS: Sixty female Wistar rats, aged 12 weeks, were included in the study. The pathology was induced by subcutaneous injection of the spinal cord homogenate. Afterwards the rats received a water solution of release-active antibodies to S100 protein (2,5 ml/kg/day, tenoten) or distilled water intragastrically during 30 days. Intramuscular injections of glatiramer acetate (4 mg/kg/day, copaxone) were used as a positive control...
2015: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/26277791/targeted-stage-specific-inflammatory-microrna-profiling-in-urine-during-disease-progression-in-experimental-autoimmune-encephalomyelitis-markers-of-disease-progression-and-drug-response
#14
Jaspreet Singh, Mandar Deshpande, Hamid Suhail, Ramandeep Rattan, Shailendra Giri
Recently, microRNAs (miRNAs) have been implicated in regulating neuroinflammatory and demyelinative responses in multiple sclerosis (MS) and its mouse model of experimental autoimmune encephalomyelitis (EAE). miRNAs have also been studied as biomarkers of disease pathology and drug-response in MS. However, no complete miRNA profiling at various stages of EAE disease has been examined, especially in the urine. We carried out a systematic analysis of miRNAs in the urine exosomes as well as in the plasma and spinal cord at pre-onset, onset and peak stages of EAE established in the chronic B6 mice model...
March 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/26214805/adherence-to-disease-modifying-drugs-among-patients-with-multiple-sclerosis-in-germany-a-retrospective-cohort-study
#15
Kerstin Hansen, Katrin Schüssel, Marita Kieble, Johanna Werning, Martin Schulz, Robert Friis, Dieter Pöhlau, Norbert Schmitz, Joachim Kugler
BACKGROUND: Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS) demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to describe adherence to four disease modifying drugs (DMDs) among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex), interferon beta-1a s.c. (Rebif), interferon beta-1b s.c. (Betaferon) and glatiramer acetate s...
2015: PloS One
https://www.readbyqxmd.com/read/26156414/therapeutic-impact-of-sphingosine-1-phosphate-receptor-signaling-in-multiple-sclerosis
#16
Kristina Candido, Henry Soufi, Mausumi Bandyopadhyay, Subhajit Dasgupta
Multiple sclerosis (MS) is a female predominant autoimmune demyelinating disease of central nervous system. The proper etiology is not clear. The existing therapies with interferon beta (Betaseron, Rebif), glatiramer acetate (copolymer 1, copaxone) are found to be promising for MS patients. The alpha-4 integrin antagonist monoclonal antibody Natalizumab has been found to decrease brain inflammation in relapsing-remitting MS via inhibition of alpha-4 beta- 1 integrinmediated mode of action of antigen -primed T cells to enter into central nervous system through blood brain barrier...
2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/26099719/development-of-flow-imaging-analysis-for-subvisible-particle-characterization-in-glatiramer-acetate
#17
Inna Levin, Shiri Zigman, Arthuer Komlosh, Juergen Kettenring
Proteins, peptides, colloids, and polymers present a rapidly growing field of pharmaceutical industry. Bringing these products into market, however, is a huge regulatory challenge, especially because many of these therapeutics are intended for parenteral administration. Physicochemical properties of such products--size, shape, surface potential, and extent of particle-particle interaction-have to be well understood and monitored throughout manufacturing, release, and stability testing. First and foremost, size distribution of subvisible particles (SVP) in these products should be reliably measured...
November 2015: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/25906331/glatiramer-acetate-40-mg-ml-in-relapsing-remitting-multiple-sclerosis-a-review
#18
REVIEW
Kate McKeage
Glatiramer acetate (Copaxone(®)) is a synthetic analogue of myelin basic protein, which is thought to be involved in the pathogenesis of multiple sclerosis (MS). The therapeutic effects of the drug in the treatment of MS are thought to be via immunomodulation and neuroprotection. Subcutaneous glatiramer acetate 20 mg/mL once daily is approved in several countries for the treatment of relapsing forms of MS. Recently, a high-concentration formulation of glatiramer acetate 40 mg/mL administered three times weekly was approved in the USA and several European countries in the same indication...
May 2015: CNS Drugs
https://www.readbyqxmd.com/read/25646307/ifn-%C3%AE-treatment-requires-b-cells-for-efficacy-in-neuroautoimmunity
#19
Ryan D Schubert, Yang Hu, Gaurav Kumar, Spencer Szeto, Peter Abraham, Johannes Winderl, Joel M Guthridge, Gabriel Pardo, Jeffrey Dunn, Lawrence Steinman, Robert C Axtell
IFN-β remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-β, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-β treatment is unclear. In this article, we show that IFN-β pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-β treatment increases the absolute number of regulatory CD19(+)CD24(++)CD38(++) transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients...
March 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25563027/-emerging-new-therapies-for-relapsing-remitting-multiple-sclerosis
#20
REVIEW
Saar Anis, Anat Achiron
For the last 20 years the classic treatment for relapsing remitting multiple sclerosis was based on injectable disease-modifying drugs, interferon-β and glatiramer acetate (copaxone). Currently, new disease-modifying drugs have been added to the clinician's arsenal with similar and even improved efficacy and safety profiles. Some of these drugs are given orally and are recommended as first line treatment. In this review we will discuss the various innovative and emerging disease-modifying drugs including the method of administration, mechanism of action, efficacy, safety and major side effects...
November 2014: Harefuah
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