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https://www.readbyqxmd.com/read/28820437/are-astrocytes-the-predominant-cell-type-for-activation-of-nrf2-in-aging-and-neurodegeneration
#1
REVIEW
Jeffrey R Liddell
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes...
August 18, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28816034/cerebrospinal-fluid-cytology-in-nonmalignant-aseptic-meningeal-disorders
#2
REVIEW
Rafael Martínez-Girón, Liron Pantanowitz
Cerebrospinal fluid cytology examination is a common and reliable primary and/or complementary procedure for the diagnosis of central nervous system (CNS) disorders. This review provides an update of aseptic meningeal disorders that may be encountered in cytopathology practice. The article covers the cytological findings and helpful ancillary studies needed of nonmalignant aseptic CNS disorders such as viral, bacterial, fungal and parasitic infections, and other noninfectious diseases, such as Mollaret´s meningitis (recurrent benign lymphocytic meningitis), Guillain-Barré syndrome, multiple Sclerosis, subarachnoid haemorrhage, and drug-induced disorders...
August 16, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/28814828/comparison-of-efficacy-and-safety-of-oral-agents-for-the-treatment-of-relapsing-remitting-multiple-sclerosis
#3
REVIEW
Cristina Guarnera, Placido Bramanti, Emanuela Mazzon
In the therapeutic scenario of disease-modifying therapies for relapsing-remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing-remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate - a superior efficacy compared to placebo...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28812229/economics-and-cost-effectiveness-of-multiple-sclerosis-therapies-in-the-usa
#4
REVIEW
Daniel M Hartung
Multiple sclerosis (MS) is a disabling, chronic disease that imposes a significant economic burden on patients and the US healthcare system. The largest cost component for individuals with MS are prescription drugs, specifically disease-modifying therapies (DMTs). Despite an increase in the number and diversity of DMTs over the past 10 years, acquisition costs for all DMTs have escalated dramatically at rates substantially higher than medical inflation. Currently, costs for most DMTs exceed $70,000 a year. Recent cost-effectiveness studies suggest the cost for nearly all DMTs exceeds generally accepted thresholds for what is considered a good value in the USA, even after factoring expected rebates...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#5
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28803486/daclizumab-for-the-treatment-of-adults-with-relapsing-forms-of-multiple-sclerosis
#6
Michael Osherov, Ron Milo
The goal of the article is to review the mechanism of action and the use of daclizumab, a humanized monoclonal antibody (mAb) against the alpha subunit of the high affinity interleukin-2 (IL-2) receptor, in the treatment of Multiple Sclerosis (MS). Areas covered: PubMed was searched for the terms "daclizumab" and "multiple sclerosis". The mechanisms of action, pharmacokinetics and pharmacodynamics, major studies, side effects and drug interactions of daclizumab in MS are discussed. Expert commentary: Monthly daclizumab-beta [DAC-beta, formerly daclizumab high yield process (DAC HYP), approved as ZINBRYTA®, which has a different form and structure than an earlier form of daclizumab], is an effective and convenient treatment option for patients with relapsing forms of MS who have failed other treatment, or as a first-line option in highly active MS patients...
August 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28794248/anti-inflammatory-disease-modifying-treatment-and-short-term-disability-progression-in-spms
#7
Johannes Lorscheider, Vilija G Jokubaitis, Tim Spelman, Guillermo Izquierdo, Alessandra Lugaresi, Eva Havrdova, Dana Horakova, Maria Trojano, Pierre Duquette, Marc Girard, Alexandre Prat, François Grand'Maison, Pierre Grammond, Eugenio Pucci, Cavit Boz, Patrizia Sola, Diana Ferraro, Daniele Spitaleri, Jeanette Lechner-Scott, Murat Terzi, Vincent Van Pesch, Gerardo Iuliano, Roberto Bergamaschi, Cristina Ramo-Tello, Franco Granella, Celia Oreja-Guevara, Helmut Butzkueven, Tomas Kalincik
OBJECTIVE: To investigate the effect of disease-modifying treatment on short-term disability outcomes in secondary progressive multiple sclerosis (SPMS). METHODS: Using MSBase, an international cohort study, we previously validated a highly accurate definition of SPMS. Here, we identified patients in MSBase who were either untreated or treated with a disease-modifying drug when meeting this definition. Propensity score matching was used to select subpopulations with comparable baseline characteristics...
August 9, 2017: Neurology
https://www.readbyqxmd.com/read/28791401/implications-of-white-matter-damage-in-amyotrophic-lateral-sclerosis-review
#8
Ting Zhou, Tina Khorshid Ahmad, Kiana Gozda, Jessica Truong, Jiming Kong, Michael Namaka
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal‑glial interactions...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28789625/association-between-multiple-sclerosis-cancer-risk-and-immunosuppressant-treatment-a-cohort-study
#9
Paolo Ragonese, Paolo Aridon, Giulia Vazzoler, Maria Antonietta Mazzola, Vincenzina Lo Re, Marianna Lo Re, Sabrina Realmuto, Simona Alessi, Marco D'Amelio, Giovanni Savettieri, Giuseppe Salemi
BACKGROUND: The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs. METHODS: We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS...
August 8, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28783872/evaluation-of-potential-drug-drug-interaction-between-delayed-release-dimethyl-fumarate-and-a-commonly-used-oral-contraceptive-norgestimate-ethinyl-estradiol-in-healthy-women
#10
Bing Zhu, Ivan Nestorov, Guolin Zhao, Venkata Meka, Mark Leahy, Jeanelle Kam, Sarah I Sheikh
Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed)...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28776214/-real-world-evidence-benefits-and-limitations-in-multiple-sclerosis-research
#11
REVIEW
T Ziemssen, D Rothenbacher, J Kuhle, T Berger
BACKGROUND: Real-world evidence (RWE) expands the data obtained in randomized clinical trials (RCTs), which are based on both homogeneous selected patient groups and limited study durations, to long-term experiences in clinical routine. In particular, chronic diseases such as multiple sclerosis (MS) with both heterogeneous pathologies and a growing number of therapeutic options require a careful RWE-based assessment of long-term efficacy and safety parameters. OBJECTIVE: This review presents RWE data sources applied in MS research and discusses potential quality standards...
August 3, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#12
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28772190/an-antigen-specific-semi-therapeutic-treatment-with-local-delivery-of-tolerogenic-factors-through-a-dual-sized-microparticle-system-blocks-experimental-autoimmune-encephalomyelitis
#13
Jonathan J Cho, Joshua M Stewart, Theodore T Drashansky, Maigan A Brusko, Ashley N Zuniga, Kyle J Lorentsen, Benjamin G Keselowsky, Dorina Avram
Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release...
July 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28762877/rituximab-in-multiple-sclerosis-frequency-and-clinical-relevance-of-anti-drug-antibodies
#14
Nicky Dunn, Alexander Juto, Malin Ryner, Ali Manouchehrinia, Luca Piccoli, Katharina Fink, Fredrik Piehl, Anna Fogdell-Hahn
BACKGROUND: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. OBJECTIVE: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. METHODS: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28762192/a-comprehensive-review-on-copemyl-%C3%A2
#15
REVIEW
Pietro Annovazzi, Antonio Bertolotto, Vincenzo Brescia Morra, Claudio Gasperini, Enrico Montanari, Pierluigi Navarra, Francesco Patti, Maria Pia Sormani, Angelo Ghezzi
Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs...
July 31, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28758631/statins-are-ineffective-at-reducing-neuroinflammation-or-prolonging-survival-in-scrapie-infected-mice
#16
James A Carroll, Brent Race, Katie Phillips, James F Striebel, Bruce Chesebro
Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28756575/evaluating-the-safety-of-medication-exposures-during-pregnancy-a-case-study-of-study-designs-and-data-sources-in-multiple-sclerosis
#17
Whitney S Krueger, Mary S Anthony, Catherine W Saltus, Andrea V Margulis, Elena Rivero-Ferrer, Brigitta Monz, Ceri Hirst, David Wormser, Elizabeth Andrews
BACKGROUND: Regulatory agencies often request prospective, product-specific post-authorization pregnancy exposure registries to monitor safety during pregnancy, even though studies using existing health databases could also be employed. OBJECTIVES: Using multiple sclerosis (MS) as a case study, we evaluated various study designs and data sources previously used to study medication exposure in pregnancy. METHODS: We examined (1) strengths and limitations of study designs used for pregnancy safety studies in women exposed to MS-specific medications during pregnancy and (2) existing data sources used to conduct such studies in other disease areas...
July 29, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/28752787/the-xenopus-tadpole-an-in-vivo-model-to-screen-drugs-favoring-remyelination
#18
Abdelkrim Mannioui, Quentin Vauzanges, Jean Baptiste Fini, Esther Henriet, Somya Sekizar, Loris Azoyan, Jean Léon Thomas, David Du Pasquier, Carine Giovannangeli, Barbara Demeneix, Catherine Lubetzki, Bernard Zalc
BACKGROUND: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. OBJECTIVE: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. METHODS: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28749311/reconstitution-of-the-peripheral-immune-repertoire-following-withdrawal-of-fingolimod
#19
Mahtab Ghadiri, Leslie Fitz-Gerald, Ayman Rezk, Rui Li, Mukanthu Nyirenda, David Haegert, Paul Steven Giacomini, Amit Bar-Or, Jack Antel
BACKGROUND: Following fingolimod cessation, immune reconstitution or lack thereof may have consequences for disease rebound or safety of commencing alternative therapies. OBJECTIVE: To examine the degree and profile of peripheral blood lymphocyte reconstitution following fingolimod withdrawal. METHODS: Total lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post-cessation...
August 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28748631/reverse-translation-for-assessment-of-confidence-in-animal-models-of-multiple-sclerosis-for-drug-discovery
#20
REVIEW
Bert A 't Hart, Jon D Laman, Yolanda S Kap
No abstract text is available yet for this article.
July 27, 2017: Clinical Pharmacology and Therapeutics
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