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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/29785523/efficacy-and-safety-of-rituximab-in-relapsing-and-progressive-multiple-sclerosis-a-hospital-based-study
#1
Carmen Alcalá, F Gascón, F Pérez-Miralles, S Gil-Perotín, A Navarré, I Boscá, F Coret, B Casanova
INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment...
May 21, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#2
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29784250/update-on-pediatric-onset-multiple-sclerosis
#3
REVIEW
A Ruet
Pediatric-onset multiple sclerosis (POMS) has distinctive features compared with adult-onset multiple sclerosis (AOMS), and warrants caution despite being a rare form of MS. POMS diagnostic criteria are somewhat different from those used in AOMS, with acute disseminated encephalomyelitis being a key differential diagnosis of MS in children. Other differential diagnoses that have to be ruled out before diagnosing MS include demyelinating syndromes, autoimmune and systemic pathologies, and infectious, genetic, metabolic and neoplastic diseases...
May 18, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29779852/treatment-of-progressive-multiple-sclerosis-challenges-and-promising-perspectives
#4
REVIEW
E Maillart
Management of progressive multiple sclerosis (MS) is one of the main challenges of the new century. Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod…); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin…). Nevertheless, despite recent promising positive clinical trials, new methodological approaches for therapeutic protocols with adaptable outcomes to assess progression are still needed.
May 17, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29779849/how-much-progress-has-there-been-in-the-second-line-treatment-of-multiple-sclerosis-a-2017-update
#5
REVIEW
A Maarouf, C Boutière, A Rico, B Audoin, J Pelletier
In 1993, the US Food and Drug Administration (FDA) approved the first drug specifically for treating multiple sclerosis (MS). More than two decades later, a dozen such treatments are now available. Of these, four are considered second-line treatments for use in escalation strategies and two new drugs are currently undergoing accreditation procedures. Soon, they will provide clinicians with a range of six effective disease-modifying treatments (DMTs) to thwart the inflammatory processes in MS patients with active disease...
May 17, 2018: Revue Neurologique
https://www.readbyqxmd.com/read/29775134/csf-inflammatory-biomarkers-responsive-to-treatment-in-progressive-multiple-sclerosis-capture-residual-inflammation-associated-with-axonal-damage
#6
Jeppe Romme Christensen, Mika Komori, Marina Rode von Essen, Rikke Ratzer, Lars Börnsen, Bibi Bielekova, Finn Sellebjerg
BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#7
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29772185/therapies-for-mobility-disability-in-persons-with-multiple-sclerosis
#8
Jessica F Baird, Brian M Sandroff, Robert W Motl
Mobility disability is one of the most widespread and impactful consequences of multiple sclerosis (MS). Disease modifying drugs (DMDs) may delay the progression of disability over time; however, there is minimal evidence supporting the efficacy of DMDs for reversing mobility disability or restoring ambulatory function in persons with MS. Areas covered: This review outlines symptomatic pharmacologic and non-pharmacologic therapeutic approaches that target mobility disability with the goal of restoring and improving walking function...
May 17, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29768414/adipose-derived-mesenchymal-stem-cells-admsc-for-the-treatment-of-secondary-progressive-multiple-sclerosis-a-triple-blinded-placebo-controlled-randomized-phase-i-ii-safety-and-feasibility-study
#9
Oscar Fernández, Guillermo Izquierdo, Victoria Fernández, Laura Leyva, Virginia Reyes, Miguel Guerrero, Antonio León, Carlos Arnaiz, Guillermo Navarro, Maria Dolores Páramo, Antonio De la Cuesta, Bernat Soria, Abdelkrim Hmadcha, David Pozo, Rafael Fernandez-Montesinos, Maria Leal, Itziar Ochotorena, Patricia Gálvez, Maria Angeles Geniz, Francisco Javier Barón, Rosario Mata, Cristina Medina, Carlos Caparrós-Escudero, Ana Cardesa, Natividad Cuende
BACKGROUND: Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. PATIENTS AND METHODS: In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months...
2018: PloS One
https://www.readbyqxmd.com/read/29761737/predictive-validity-of-neda-in-the-16-and-21-year-follow-up-from-the-pivotal-trial-of-interferon-beta-1b
#10
Douglas S Goodin, Anthony T Reder, Anthony L Traboulsee, David Kb Li, Dawn Langdon, Gary Cutter, Stuart Cook, Timothy O'Donnell, Marcelo Kremenchutzky, Joel Oger, Ralf Koelbach, Christoph Pohl, Eva-Maria Wicklein
BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29758075/effectiveness-and-safety-of-rituximab-in-multiple-sclerosis-an-observational-study-from-southern-switzerland
#11
Barbara Scotti, Giulio Disanto, Rosaria Sacco, Marilu' Guigli, Chiara Zecca, Claudio Gobbi
BACKGROUND: Despite positive results from phase II and observational studies, Rituximab (RTX) is not currently approved for multiple sclerosis (MS) treatment and can only be used off-label. OBJECTIVE: To characterize MS patients treated with RTX and investigate its effectiveness and safety in a clinical practice setting. METHODS: Observational analysis of data collected from MS patients at the Neurocenter of Southern Switzerland. Relapses, EDSS worsening, MRI lesion accrual and "evidence of disease activity" (EDA) status were described by Cox regression...
2018: PloS One
https://www.readbyqxmd.com/read/29754703/progression-of-a-series-of-patients-with-relapsing-remitting-multiple-sclerosis-treated-for-7-years-with-natalizumab-using-the-no-evidence-of-disease-activity-parameter
#12
A Pato Pato, E Costa Arpín, A Rodríguez Regal, I Rodríguez Constenla, I Cimas Hernando, I Muñoz Pousa, L Naya Ríos, J R Lorenzo González, M C Amigo Jorrín, J M Prieto González
INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters...
May 10, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29751602/old-drugs-as-new-treatments-for-neurodegenerative-diseases
#13
REVIEW
Fernando Durães, Madalena Pinto, Emília Sousa
Neurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years...
May 11, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29747362/-research-progression-of-animal-models-of-idiopathic-optic-neuritis
#14
Y X Zhang, H Yang
Idiopathic optic neuritis (ON) is an idiopathic inflammatory disease of the optic nerve. The two most common types of ON are multiple sclerosis related ON and neuromyelitis optica related ON. But so far the precise mechanisms of different types of ON have been unclear and treatments are not satisfactory. Animal disease models play critical roles in the disease mechanism research. On the other hand, with more understanding about the etiology and mechanism of ON, new models mimicking different types of ON are under development...
April 11, 2018: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29742699/effect-of-photobiomodulation-treatment-in-the-sublingual-radial-artery-region-and-along-the-spinal-column-in-individuals-with-multiple-sclerosis-protocol-for-a-randomized-controlled-double-blind-clinical-trial
#15
RANDOMIZED CONTROLLED TRIAL
Tamiris da Silva, Fernanda Cordeiro da Silva, Andréa Oliver Gomes, Ariane Oliveira Viana, Marcela Letícia Leal Gonçalves, Maria Fernanda Setúbal Destro Rodrigues, Anna Carolina Ratto Tempestini Horliana, Daniela de Fátima Teixeira da Silva, Maria Cristina Chavantes, Yara Dadalti Fragoso, Luciana Prats Branco, Lara Jansiski Motta, Kristianne Porta Santos Fernandes, Raquel Agnelli Mesquita-Ferrari, Sandra Kalil Bussadori
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, for which the forms of treatment are medication and rehabilitation. However, in vitro and in vivo studies have demonstrated that photobiomodulation can be an effective treatment modality for inflammatory diseases, including MS. Photobiomodulation has a broad range of benefits, such as the avoidance of cell and tissue death, the stimulation of healing and injury repair, reductions in pain, edema and inflammation, cell proliferation, and even apoptosis...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29741648/progression-of-regional-grey-matter-atrophy-in-multiple-sclerosis
#16
Arman Eshaghi, Razvan V Marinescu, Alexandra L Young, Nicholas C Firth, Ferran Prados, M Jorge Cardoso, Carmen Tur, Floriana De Angelis, Niamh Cawley, Wallace J Brownlee, Nicola De Stefano, M Laura Stromillo, Marco Battaglini, Serena Ruggieri, Claudio Gasperini, Massimo Filippi, Maria A Rocca, Alex Rovira, Jaume Sastre-Garriga, Jeroen J G Geurts, Hugo Vrenken, Viktor Wottschel, Cyra E Leurs, Bernard Uitdehaag, Lukas Pirpamer, Christian Enzinger, Sebastien Ourselin, Claudia A Gandini Wheeler-Kingshott, Declan Chard, Alan J Thompson, Frederik Barkhof, Daniel C Alexander, Olga Ciccarelli
Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres...
May 8, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29740872/prodromal-symptoms-of-multiple-sclerosis-in-primary-care
#17
Giulio Disanto, Chiara Zecca, Sharon MacLachlan, Rosaria Sacco, Lahiru Handunnetthi, Ute C Meier, Alex Simpson, Laura McDonald, Andrea Rossi, Pascal Benkert, Jens Kuhle, Sreeram V Ramagopalan, Claudio Gobbi
OBJECTIVE: Early diagnosis and treatment initiation significantly influence long term disability outcome in multiple sclerosis (MS). We aimed at identifying prodromal symptoms of MS in primary care settings. METHODS: This was a nested case-control study comparing the occurrence of various symptoms in MS patients vs controls at 0-2, 2-5 and 5-10 years before index date (first MS record). A total of 10,204 incident MS cases were identified within the UK Clinical Practice Research Datalink (CPRD) between 01/01/1987 and 28/02/2016 (median (IQR) age=47 (39-57) years, females=7,308 (71...
May 8, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29737455/current-and-future-use-of-chloroquine-and-hydroxychloroquine-in-infectious-immune-neoplastic-and-neurological-diseases-a-mini-review
#18
REVIEW
Domenico Plantone, Tatiana Koudriavtseva
The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects...
May 8, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29735753/metabolism-and-disposition-of-siponimod-a-novel-selective-s1p1-s1p5-agonist-in-healthy-volunteers-and-in-vitro-identification-of-human-cytochrome-p450-enzymes-involved-in-its-oxidative-metabolism
#19
Ulrike Glaenzel, Yi Jin, Robert Nufer, Wenkui Li, Kirsten Schroer, Sylvie Adam-Stitah, Sjoerd Peter van Marle, Eric Legangneux, Hubert Borell, Alexander David James, Axel Meissner, Gian Camenisch, Anne Gardin
Siponimod, a next generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis. We investigated the absorption, distribution, metabolism and excretion of a single oral dose of [14 C]siponimod 10 mg in four healthy male subjects. Mass balance, blood and plasma radioactivity, and plasma siponimod concentrations were measured. Metabolite profiles were determined in plasma, urine and feces. Metabolite structures were elucidated using mass spectrometry and comparison with reference compounds...
May 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29728570/identification-of-brain-antigens-recognized-by-autoantibodies-in-experimental-autoimmune-encephalomyelitis-induced-animals-treated-with-etomoxir-or-interferon-%C3%AE
#20
Anne Skøttrup Mørkholt, Kenneth Kastaniegaard, Michael Sloth Trabjerg, Gopana Gopalasingam, Wanda Niganze, Agnete Larsen, Allan Stensballe, Søren Nielsen, John Dirk Nieland
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self-proteins. The involvement of autoantibodies in MS pathogenesis has been suggested to initiate and drive progression of inflammation; however, the etiology of MS remains unknown. The effect of etomoxir and interferon-β (IFN-β) was examined in an experimental-autoimmune-encephalomyelitis (EAE) model of MS...
May 4, 2018: Scientific Reports
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