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https://www.readbyqxmd.com/read/27909192/the-more-the-merrier-scoring-statistics-and-animal-welfare-in-experimental-autoimmune-encephalomyelitis
#1
Pushpalatha Palle, Filipa M Ferreira, Axel Methner, Thorsten Buch
Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants...
December 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27904656/the-berlin-treatment-algorithm-recommendations-for-tailored-innovative-therapeutic-strategies-for-multiple-sclerosis-related-fatigue
#2
REVIEW
Christian Veauthier, Helge Hasselmann, Stefan M Gold, Friedemann Paul
More than 80% of multiple sclerosis (MS) patients suffer from fatigue. Despite this, there are few therapeutic options and evidence-based pharmacological treatments are lacking. The associated societal burden is substantial (MS fatigue is a major reason for part-time employment or early retirement), and at least one out of four MS patients view fatigue as the most burdensome symptom of their disease. The mechanisms underlying MS-related fatigue are poorly understood, and objective criteria for distinguishing and evaluating levels of fatigue and tiredness have not yet been developed...
2016: EPMA Journal
https://www.readbyqxmd.com/read/27904430/natalizumab-related-progressive-multifocal-leukoencephalopathy-immune-reconstitution-inflammatory-syndrome-a-case-report-highlighting-clinical-and-mri-features
#3
Bela Purohit, Eranga Ganewatte, Spyros S Kollias
Multiple sclerosis (MS) patients treated with natalizumab often face the uncommon but severe complication of developing progressive multifocal leukoencephalopathy (PML). PML may be further complicated by immune reconstitution inflammatory syndrome (IRIS) after the removal of the drug. Since both PML and IRIS are associated with high morbidity and mortality rates, early clinical and radiological diagnosis of these complications is of paramount importance. Here, we report a case of an adult male patient who was diagnosed with PML after receiving natalizumab therapy for 6 years for the treatment of MS...
September 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/27894870/a-benzo-b-thiophene-based-selective-type-4-s1p-receptor-agonist
#4
Wooyoung Hur, Hugh Rosen, Nathanael S Gray
S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-selective agonists have been reported for each S1PR isotype, some of which are used as pharmacological tools for functional studies. Here we report the discovery and initial characterization of compound 5c, a benzo[b]thiophene amino carboxylate which exhibits potent and selective agonist activity for S1PR4...
November 18, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27892723/optimization-and-stratification-of-multiple-sclerosis-treatment-in-fast-developing-economic-countries-a-perspective-from-qatar
#5
Dirk Deleu, Boulenouar Mesraoua, Hisham El Khider, Beatriz Canibano, Gayane Melikyan, Hassan Al Hail, Noha Mhjob, Anjushri Bhagat, Faiza Ibrahim, Yolande Hanssens
OBJECTIVE: The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS conform to the healthcare system in a fast-developing economic country such as Qatar...
November 28, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27891572/safety-concerns-and-risk-management-of-multiple-sclerosis-therapies
#6
REVIEW
P Soelberg Sorensen
Currently, more than ten drugs have been approved for treatment of relapsing-remitting multiple sclerosis (MS). Newer treatments may be more effective, but have less favorable safety record. Interferon-β preparations and glatiramer acetate treatment require frequent subcutaneous or intramuscular injections and are only moderately effective, but have very rarely life-threatening adverse effects, whereas teriflunomide and dimethyl fumarate are administered orally and have equal or better efficacy, but have more potentially severe adverse effects...
November 27, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27890706/the-sphingosine-1-phosphate-receptor-a-novel-therapeutic-target-for-multiple-sclerosis-and-other-autoimmune-diseases
#7
REVIEW
Yang Mao-Draayer, Jeffrey Sarazin, David Fox, Elena Schiopu
Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]). for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27889192/evolving-concepts-in-the-treatment-of-relapsing-multiple-sclerosis
#8
REVIEW
Giancarlo Comi, Marta Radaelli, Per Soelberg Sørensen
In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started as early as possible and aim to re-establish the normal complex interactions in the immune system...
November 23, 2016: Lancet
https://www.readbyqxmd.com/read/27889191/progressive-multiple-sclerosis-prospects-for-disease-therapy-repair-and-restoration-of-function
#9
REVIEW
Daniel Ontaneda, Alan J Thompson, Robert J Fox, Jeffrey A Cohen
Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity...
November 23, 2016: Lancet
https://www.readbyqxmd.com/read/27886183/fingolimod-therapeutic-mechanisms-and-ocular-adverse-effects
#10
REVIEW
P Mandal, A Gupta, W Fusi-Rubiano, P A Keane, Y Yang
Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur...
November 25, 2016: Eye
https://www.readbyqxmd.com/read/27885448/cognitive-dysfunction-in-patients-with-multiple-sclerosis-treated-with-first-line-disease-modifying-therapy-a-multi-center-controlled-study-using-the-bicams-battery
#11
Bilge Piri Cinar, Görkem Kösehasanoğulları, Pinar Yigit, Serkan Ozakbas
Multiple sclerosis (MS) can impair cognitive functions even in the early stages. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery is very short and highly sensitive and can be used to evaluate cognitive status in the disease. Several clinical trials have shown beneficial effects of disease-modifying drugs (DMDs) on long-term cognitive measures which may even reduce cognitive deficits in MS patients. Relapsing remitting MS patients using DMDs were enrolled in the study and monitored for 12 months...
November 24, 2016: Neurological Sciences
https://www.readbyqxmd.com/read/27882831/quantifying-differences-in-health-care-consumption-for-the-management-of-multiple-sclerosis-within-privately-and-publicly-insured-health-care-programs
#12
Terrie Livingston, Monica Fay, Ravi Iyer, Wendy Wells, Michael W Pill
BACKGROUND: Multiple sclerosis (MS) is a chronic and debilitating disease of the central nervous system that affects more than 570,000 persons in the United States and 2.3 million worldwide. Since most individuals experience initial symptoms between the ages of 20 and 40 years, MS can have a significant effect on health care consumption, quality of life, productivity, and employment over the long-term disease course. Opportunities exist to better understand how benefit design and other nonclinical factors can affect health care delivery and associated costs...
December 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27882538/gene-therapy-with-mesenchymal-stem-cells-expressing-ifn%C3%A3-ameliorates-neuroinflammation-in-experimental-models-of-multiple-sclerosis
#13
C Marin-Bañasco, K Benabdellah, C Melero-Jerez, B Oliver, M J Pinto-Medel, I Hurtado-Guerrero, F de Castro, D Clemente, O Fernández, F Martin, L Leyva, M Suardíaz
BACKGROUND AND PURPOSE: Recombinant IFNß is one of the first line treatments in multiple sclerosis (MS), despite its lack of efficiency in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, taking advantage of their pathotropism ability, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882351/activity-of-nav1-2-promotes-neurodegeneration-in-an-animal-model-of-multiple-sclerosis
#14
Benjamin Schattling, Walid Fazeli, Birgit Engeland, Yuanyuan Liu, Holger Lerche, Dirk Isbrandt, Manuel A Friese
Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along demyelinated axons contributes to neurodegeneration by increasing neuroaxonal sodium influx and energy demand during CNS inflammation...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27880972/interferons-beta-versus-glatiramer-acetate-for-relapsing-remitting-multiple-sclerosis
#15
REVIEW
Loredana La Mantia, Carlo Di Pietrantonj, Marco Rovaris, Giulio Rigon, Serena Frau, Francesco Berardo, Anna Gandini, Anna Longobardi, Bianca Weinstock-Guttman, Alberto Vaona
BACKGROUND: Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 20 years ago for the treatment of multiple sclerosis (MS). DMTs' prescription rates as first or switching therapies and their costs have both increased substantially over the past decade. As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality of life. As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared...
November 24, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27879549/fingolimod-use-for-the-treatment-of-multiple-sclerosis-in-a-clinical-practice-setting-in-madrid
#16
Victoria Galán Sánchez-Seco, Ignacio Casanova-Peño, Roberto Álvarez-Lafuente, Mónica Sánchez-Jiménez, Ángel García-Martínez, María Inmaculada Domínguez-Mozo, Ana María Arias-Leal, Marta García-Montojo, Rafael Arroyo-González
OBJECTIVE: To assess the effectiveness and safety of fingolimod use in a Spanish clinical practice setting. METHODS: Retrospective study with multiple sclerosis patients who received at least 1 fingolimod dose between January 2004 and January 2015. Effectiveness and safety data were collected during the entire treatment of each patient. Analysis was performed for the total population and stratified according to prior treatment, sex, and age at treatment initiation...
November 22, 2016: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/27878443/real-world-effectiveness-of-natalizumab-and-fingolimod-compared-with-self-injectable-drugs-in-non-responders-and-in-treatment-na%C3%A3-ve-patients-with-multiple-sclerosis
#17
Luca Prosperini, Francesco Saccà, Cinzia Cordioli, Antonio Cortese, Fabio Buttari, Simona Pontecorvo, Assunta Bianco, Serena Ruggieri, Shalom Haggiag, Vincenzo Brescia Morra, Ruggero Capra, Diego Centonze, Giancarlo Di Battista, Elisabetta Ferraro, Ada Francia, Simonetta Galgani, Claudio Gasperini, Enrico Millefiorini, Massimiliano Mirabella, Carlo Pozzilli
In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i...
November 22, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27876009/lifestyle-medication-and-socio-demographic-determinants-of-mental-and-physical-health-related-quality-of-life-in-people-with-multiple-sclerosis
#18
George A Jelinek, Alysha M De Livera, Claudia H Marck, Chelsea R Brown, Sandra L Neate, Keryn L Taylor, Tracey J Weiland
BACKGROUND: Health-related quality of life (QOL) is a key outcome for people with multiple sclerosis (MS). While modifiable lifestyle factors, like smoking, physical activity and vitamin D, have strong associations with development and progression of MS, few studies have examined such associations with QOL. METHODS: Using patient-reported data from 2312 people with MS from 54 countries, regression models explored associations of socio-demographic, therapeutic and lifestyle factors with QOL, using the Multiple Sclerosis Quality of Life-54 (MSQOL-54)...
November 22, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27866120/evidence-based-guidelines-on-the-therapeutic-use-of-transcranial-direct-current-stimulation-tdcs
#19
REVIEW
Jean-Pascal Lefaucheur, Andrea Antal, Samar S Ayache, David H Benninger, Jérôme Brunelin, Filippo Cogiamanian, Maria Cotelli, Dirk De Ridder, Roberta Ferrucci, Berthold Langguth, Paola Marangolo, Veit Mylius, Michael A Nitsche, Frank Padberg, Ulrich Palm, Emmanuel Poulet, Alberto Priori, Simone Rossi, Martin Schecklmann, Sven Vanneste, Ulf Ziemann, Luis Garcia-Larrea, Walter Paulus
A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction...
October 29, 2016: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/27836779/contribution-of-cholesterol-and-oxysterols-to-the-pathophysiology-of-parkinson-s-disease
#20
REVIEW
Margaux Doria, Lucie Maugest, Thibault Moreau, Gérard Lizard, Anne Vejux
Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (Lewy bodies)...
November 9, 2016: Free Radical Biology & Medicine
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