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https://www.readbyqxmd.com/read/28724581/mri-evidence-of-acute-inflammation-in-leukocortical-lesions-of-patients-with-early-multiple-sclerosis
#1
Josefina Maranzano, David A Rudko, Kunio Nakamura, Stuart Cook, Diego Cadavid, Leo Wolansky, Douglas L Arnold, Sridar Narayanan
OBJECTIVE: To identify gadolinium-enhancing lesions affecting the cortex of patients with early multiple sclerosis (MS) and to describe the frequency and evolution of these lesions. METHODS: We performed a retrospective, observational, longitudinal analysis of MRI scans collected as part of the Betaseron vs Copaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3T MRI Endpoints (BECOME) study. Seventy-five patients with early-stage MS were scanned monthly, over a period of 12-24 months, using 3T MRI after administration of triple-dose gadolinium...
July 19, 2017: Neurology
https://www.readbyqxmd.com/read/28706565/once-daily-glatiramer-acetate-decreases-magnetic-resonance-imaging-disease-activity-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis
#2
Takashi Yamamura, Natalia Ashtamker, David Ladkani, Toshiyuki Fukazawa, Hideki Houzen, Masami Tanaka, Toshiro Miura, Volker Knappertz
OBJECTIVE: Multiple sclerosis (MS) prevalence, clinical patterns, and treatment responses vary between races and geographical latitudes. Glatiramer acetate (GA; Copaxone) has provided a safe, effective treatment option for relapsing-remitting MS patients in the USA, European nations, and other countries for decades. The objective of the present study was to assess the safety and efficacy of GA in reducing magnetic resonance imaging disease activity in Japanese patients with active relapsing-remitting MS...
May 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28569182/a-pharmacogenetic-signature-of-high-response-to-copaxone-in-late-phase-clinical-trial-cohorts-of-multiple-sclerosis
#3
Colin J Ross, Fadi Towfic, Jyoti Shankar, Daphna Laifenfeld, Mathis Thoma, Matthew Davis, Brian Weiner, Rebecca Kusko, Ben Zeskind, Volker Knappertz, Iris Grossman, Michael R Hayden
BACKGROUND: Copaxone is an efficacious and safe therapy that has demonstrated clinical benefit for over two decades in patients with relapsing forms of multiple sclerosis (MS). On an individual level, patients show variability in their response to Copaxone, with some achieving significantly higher response levels. The involvement of genes (e.g., HLA-DRB1*1501) with high inter-individual variability in Copaxone's mechanism of action (MoA) suggests the potential contribution of genetics to treatment response...
May 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28431621/two-decades-of-glatiramer-acetate-from-initial-discovery-to-the-current-development-of-generics
#4
REVIEW
Bianca Weinstock-Guttman, Kavita V Nair, Joseph L Glajch, Tanmoy C Ganguly, Daniel Kantor
Multiple sclerosis (MS) is a chronic, incurable, inflammatory disease of the central nervous system (CNS). In the United States, several US Food and Drug Administration (FDA)-approved disease-modifying treatments (DMTs) are available, including glatiramer acetate (GA; Copaxone®), one of the most longstanding treatments. GA was discovered serendipitously in the late 1960s/early 1970s while attempting to produce a synthetic antigen capable of inducing experimental autoimmune encephalomyelitis (EAE), an animal model of autoimmune inflammatory CNS disorders, including MS...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28427690/factors-associated-with-adherence-to-disease-modifying-therapy-in-multiple-sclerosis-an-observational-survey-from-a-referral-center-in-lithuania
#5
Neringa Duchovskiene, Dalia Mickeviciene, Giedre Jurkeviciene, Birute Dirziuviene, Renata Balnyte
AIM OF THE STUDY: To investigate adherence to disease modifying therapy (DMT) in Lithuanian population of multiple sclerosis patients and factors associated to it. METHODS: Patients receiving one of the following DMT's: Interferon β 1a (Rebif) 44 micrograms three times a week subdermally (s/c) or Interferon β 1a (Avonex) 30 micrograms weekly intramuscularly (i/m), or Interferon β 1b (Betaferon, Extavia) 250 micrograms once in two days s/c, or Glatiramer acetate (Copaxone) 20mg daily s/c, were presented with a questionnaire inquiring their demographic and clinical characteristics and adherence to treatment profile, as well as HAD scale and SF-36 questionnaire...
April 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28240190/demonstration-of-biological-and-immunological-equivalence-of-a-generic-glatiramer-acetate
#6
Josephine D D Alessandro, Kevin Garofalo, Ganlin Zhao, Christopher Honan, Jay Duffner, Ishan Capila, Ian Fier, Ganesh Kaundinya, Daniel Kantor, Tanmoy Ganguly
In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone. In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, antigen-presenting cell biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#7
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
July 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#8
REVIEW
M von Euler Chelpin, T Vorup-Jensen
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
May 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28195026/from-academic-laboratory-to-the-market-disclosed-and-undisclosed-narratives-of-commercialization
#9
Adi Sapir, Amalya L Oliver
This paper examines how the Weizmann Institute of Science has been telling the story of the successful commercialization of a scientific invention, through its corporate communication channels, from the early 1970s to today. The paper aims to shed light on the transformation processes by which intellectual-property-based commercialization activities have become widely institutionalized in universities all over the world, and on the complexities, ambiguities and tensions surrounding this transition. We look at the story of the scientific invention of Copolymer-1 at the Weizmann Institute of Science and its licensing to Teva Pharmaceutical Industries, which subsequently developed the highly successful drug Copaxone for the treatment of multiple sclerosis...
February 2017: Social Studies of Science
https://www.readbyqxmd.com/read/28090798/switching-from-branded-to-generic-glatiramer-acetate-15-month-gate-trial-extension-results
#10
Krzysztof Selmaj, Frederik Barkhof, Anna N Belova, Christian Wolf, Evelyn Rw van den Tweel, Janine Jl Oberyé, Roel Mulder, David F Egging, Norbert P Koper, Jeffrey A Cohen
BACKGROUND: Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone(®) (GATE) trial. OBJECTIVE: To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment. METHODS: A total of 729 patients received GTR 20 mg/mL daily...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27785417/metabolic-response-to-glatiramer-acetate-therapy-in-multiple-sclerosis-patients
#11
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
#12
RANDOMIZED CONTROLLED TRIAL
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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