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https://www.readbyqxmd.com/read/29455558/investigational-immunosuppressants-in-early-stage-clinical-trials-for-the-treatment-of-multiple-sclerosis
#1
Alberto Gajofatto, Marco Turatti
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS...
February 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29454607/italian-wikipedia-and-epilepsy-an-infodemiological-study-of-online-information-seeking-behavior
#2
Francesco Brigo, Simona Lattanzi, Giorgia Giussani, Laura Tassi, Nicola Pietrafusa, Carlo Andrea Galimberti, Raffaele Nardone, Nicola Luigi Bragazzi, Oriano Mecarelli
Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017...
February 14, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29449328/cladribine-for-multiple-sclerosis
#3
(no author information available yet)
In the UK, there are twelve disease-modifying drugs licensed for various forms of multiple sclerosis (MS), of which three are oral therapies. An oral formulation of cladribine (Mavenclad - Merck Serono Europe Limited) was recently licensed by the European Medicines Agency (EMA) for the treatment of adult patients with highly active relapsing MS. 1,2 It is claimed to be "an innovatively simple approach" for treating this form of MS and "the only disease modifying therapy that can deliver and sustain 4 years of disease control with a maximum of 20 days oral treatment in the first 2 years...
February 2018: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/29446144/animal-models-of-multiple-sclerosis-focus-on-experimental-autoimmune-encephalomyelitis
#4
REVIEW
Ivana Bjelobaba, Vesna Begovic-Kupresanin, Sanja Pekovic, Irena Lavrnja
Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients...
February 15, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29445162/mycn-drives-glutaminolysis-in-neuroblastoma-and-confers-sensitivity-to-an-ros-augmenting-agent
#5
Tingting Wang, Lingling Liu, Xuyong Chen, Yuqing Shen, Gaojian Lian, Nilay Shah, Andrew M Davidoff, Jun Yang, Ruoning Wang
Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer, is featured by frequent genomic amplification of MYCN, a member of the Myc oncogene family that is primarily expressed in the early stage of embryonic development and required for neural crest development. Here we report that an enriched glutaminolysis gene signature is associated with MYCN amplification in children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444620/differential-anxiety-like-responses-in-nod-shiltj-and-c57bl-6j-mice-following-experimental-autoimmune-encephalomyelitis-induction-and-oral-gavage
#6
Pece Kocovski, Phuc T Dang, Claretta S D'Souza, Christopher E Stamper, Matthew W Hale, Jacqueline M Orian
Oral gavage is commonly used in pre-clinical drug evaluation, but is potentially aversive and may induce behavioral effects independent of compounds under investigation. This study examined the combined effects of repeated oral gavage and disease induction on anxiety-like behavior in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. The C57BL/6J and NOD/ShiLtJ EAE variants were exposed to sham-EAE induction or untreated control conditions, and either daily oral gavage or home cage conditions...
January 1, 2018: Laboratory Animals
https://www.readbyqxmd.com/read/29436244/improving-multiple-sclerosis-management-and-collecting-safety-information-in-the-real-world-the-msds3d-software-approach
#7
Rocco Haase, Maria Wunderlich, Anja Dillenseger, Raimar Kern, Katja Akgün, Tjalf Ziemssen
For safety evaluation, randomized controlled trials (RCTs) are not fully able to identify rare adverse events. The richest source of safety data lies in the post-marketing phase. Real-world evidence (RWE) and observational studies are becoming increasingly popular because they reflect usefulness of drugs in real life and have the ability to discover uncommon or rare adverse drug reactions. Areas covered: Adding the documentation of psychological symptoms and other medical disciplines, the necessity for a complex documentation becomes apparent...
February 13, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29429076/cardiovascular-autonomic-dysfunction-link-between-multiple-sclerosis-osteoporosis-and-neurodegeneration
#8
REVIEW
Zohara Sternberg
The high prevalence of osteoporosis, observed in multiple sclerosis (MS) patients, has been attributed to reduced mobility and or the use of disease-modifying drugs. However, MS-impaired cardiovascular autonomic nervous system (ANS) function has the potential of reducing bone mass density (BMD) by altering the expression and/or function of the neuronal, systemic, and local mediators of bone remodeling. This review describes the complex regulation of bone homeostasis with a focus on MS, providing evidence that ANS dysfunction and low BMD are intertwined with MS inflammatory and neurodegenerative processes, and with other MS-related morbidities, including depression, fatigue, and migraine...
February 10, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29429031/the-changing-multiple-sclerosis-treatment-landscape-impact-of-new-drugs-and-treatment-recommendations
#9
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#10
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29424466/differential-local-tissue-permissiveness-influences-the-final-fate-of-gpr17-expressing-oligodendrocyte-precursors-in-two-distinct-models-of-demyelination
#11
Giusy T Coppolino, Davide Marangon, Camilla Negri, Gianluca Menichetti, Marta Fumagalli, Paolo Gelosa, Leda Dimou, Roberto Furlan, Davide Lecca, Maria P Abbracchio
Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2 xCAG-eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult...
February 9, 2018: Glia
https://www.readbyqxmd.com/read/29411688/preservation-of-neuronal-function-as-measured-by-clinical-and-mri-endpoints-in-relapsing-remitting-multiple-sclerosis-how-effective-are-current-treatment-strategies
#12
Christiane Graetz, Sergiu Groppa, Frauke Zipp, Nelly Siller
Approved medications for relapsing-remitting multiple sclerosis have shown to be effective in terms of their anti-inflammatory potential. However, it is also crucial to evaluate what long-term effects a patient can expect from current MS drugs in terms of preventing neurodegeneration. Here we aim to provide an overview of the current treatment strategies in MS with a specific focus on potential neuroprotective effects. Areas covered: Randomized, double-blind and placebo or referral-drug controlled phase 2a/b and phase 3 trials were examined; non-blinded phase 4 studies (extension studies) were included to provide long-term data, if not otherwise available...
February 7, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29410157/regulatory-accepted-drug-development-tools-are-needed-to-accelerate-innovative-cns-disease-treatments
#13
REVIEW
Stephen P Arnerić, Volker D Kern, Diane T Stephenson
Central Nervous System (CNS) diseases represent one of the most challenging therapeutic areas for successful drug approvals. Developing quantitative biomarkers as Drug Development Tools (DDTs) can catalyze the path to innovative treatments, and improve the chances of drug approvals. Drug development and healthcare management requires sensitive, reliable, validated, and regulatory accepted biomarkers and endpoints. This review highlights the regulatory paths and considerations for developing DDTs required to advance biomarker and endpoint use in clinical development (e...
January 30, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29407174/butylphthalide-ameliorates-experimental-autoimmune-encephalomyelitis-by-suppressing-pgam5-induced-necroptosis-and-inflammation-in-microglia
#14
Ying Wang, Yue Bi, Zhilun Xia, Wei Shi, Bo Li, Bin Li, Liping Chen, Li Guo
Multiple sclerosis (MS) is a long-lasting autoimmune disease of the central nervous system. Currently, the etiology of MS is not known. Experimental autoimmune encephalomyelitis (EAE), has been recognized as the most widely used animal models to study the molecular mechanisms underlying MS and the efficacy of potential drugs for treatment of MS. In the present study, we found that Dl-3-n-butylphthalide (NBP), a neuroprotective drug in ischemic brain injury, prevented development of disease in experimental autoimmune encephalomyelitis (EAE) and significantly reduced inflammatory factors and necroptosis-associated genes, including PGAM5 in the spinal cord tissues...
February 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29406017/examining-the-effectiveness-of-acetylcholinesterase-inhibitors-and-stimulant-based-medications-for-cognitive-dysfunction-in-multiple-sclerosis-a-systematic-review-and-meta-analysis
#15
REVIEW
Jack Cotter, Nils Muhlert, Anahita Talwar, Kiri Granger
We sought to examine the effectiveness of acetylcholinesterase inhibitors (AChEIs) and stimulant-based medications for improving cognitive performance in patients with multiple sclerosis (MS). An electronic database search was conducted on 25th March 2017. Eligible studies were double-blind, randomised, placebo-controlled trials that examined the efficacy of compounds that act primarily as AChEIs or stimulants (administered daily for ≥1 week) on cognitive outcome measures in patients with MS. Where suitable data was reported, we generated effect sizes and corresponding 95% confidence intervals and performed meta-analyses using random-effects models to investigate the effectiveness of these drug types across cognitive domains...
March 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29399053/an-epidemiological-study-on-the-course-of-disease-and-therapeutic-considerations-in-relapsing-remitting-multiple-sclerosis-patients-receiving-injectable-first-line-disease-modifying-therapies-in-germany-epidem
#16
Stephan Schmidt, Jürgen Koehler, Christine Winterstein, Petra Schicklmaier, Boris Kallmann
Background: In relapsing-remitting multiple sclerosis (RRMS), 'no evidence of disease activity' (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. Methods: EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29399047/decreased-platelet-number-in-multiple-sclerosis-during-alemtuzumab-infusion-a-common-transient-and-clinically-silent-phenomenon
#17
Marco Puthenparampil, Francesca Rinaldi, Lisa Federle, Chiara Cazzola, Paola Perini, Paolo Gallo
Background: The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods: A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49)...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29395738/th17%C3%A2-cells-%C3%AE-%C3%AE-t-cells-and-their-interplay-in-eae-and-multiple-sclerosis
#18
REVIEW
Aoife M McGinley, Sarah C Edwards, Mathilde Raverdeau, Kingston H G Mills
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) that shares many features with the human disease. This review will focus on the role of IL-17-secreting CD4 and γδ T cells in EAE and MS, the plasticity of Th17 cells in vivo and the application of these findings to the understating of the pathogenesis and the development of new treatments for MS. There is convincing evidence that IL-17-secreting CD4 T cells (Th17 cells) and IL-17-secreting γδ T cells play a critical pathogenic role in central nervous system (CNS) inflammation in EAE and MS...
January 21, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29392457/the-long-term-impact-of-early-treatment-of-multiple-sclerosis-on-the-risk-of-disability-pension
#19
Erik Landfeldt, Anna Castelo-Branco, Axel Svedbom, Emil Löfroth, Andrius Kavaliunas, Jan Hillert
OBJECTIVE: The objective of this retrospective, observational study was to estimate the long-term impact of early treatment of multiple sclerosis (MS) on the risk of disability pension. METHODS: Our cohort comprised patients with MS in Sweden, identified in a nationwide disease-specific register (the Swedish Multiple Sclerosis Registry), who started treatment with a disease-modifying drug (DMD) between January 1, 2002, and December 31, 2012. We analyzed the association between time from onset of MS to treatment initiation and full-time disability pension using survival analysis...
February 1, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29389745/safety-and-efficacy-of-rituximab-experience-of-a-single-multiple-sclerosis-center
#20
Brett Alldredge, Allison Jordan, Jaime Imitola, Michael K Racke
OBJECTIVES: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. B cells play an important pathogenic role in MS. Rituximab (RTX), a B-cell depleting drug, has been used to treat MS and neuromyelitis optica (NMO). Patient characteristics, safety, and efficacy measures are reviewed to ascertain the therapeutic benefit and safety of RTX in a real-world setting with long-term follow-up. METHODS: This is a retrospective chart review of patients who received RTX at The Ohio State University's MS clinic from January 2005 to October 2016...
January 31, 2018: Clinical Neuropharmacology
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