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https://www.readbyqxmd.com/read/28523586/ocrelizumab-first-global-approval
#1
James E Frampton
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28516804/spinal-cord-atrophy-as-a-primary-outcome-measure-in-phase-ii-trials-of-progressive-multiple-sclerosis
#2
Niamh Cawley, Carmen Tur, Ferran Prados, Domenico Plantone, Hugh Kearney, Khaled Abdel-Aziz, Sebastian Ourselin, Claudia Am Gandini Wheeler-Kingshott, David H Miller, Alan J Thompson, Olga Ciccarelli
OBJECTIVES: To measure the development of spinal cord (SC) atrophy over 1 year in patients with progressive multiple sclerosis (PMS) and determine the sample sizes required to demonstrate a reduction in spinal cord cross-sectional area (SC-CSA) as an outcome measure in clinical trials. METHODS: In total, 44 PMS patients (26 primary progressive multiple sclerosis (PPMS), 18 secondary progressive multiple sclerosis (SPMS)) and 29 healthy controls (HCs) were studied at baseline and 12 months...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28514773/a-feasibility-study-of-the-full-outpatient-conduction-of-hematopoietic-transplants-in-persons-with-multiple-sclerosis-employing-autologous-non-cryopreserved-peripheral-blood-stem-cells
#3
Guillermo J Ruiz-Argüelles, Andrés A León-Peña, Mónica León-González, Ana Karen Nuñez-Cortes, Juan Carlos Olivares-Gazca, Iván Murrieta-Alvarez, Jocelyn Vargas-Espinosa, Emilio Medina-Ceballos, Yahveth Cantero-Fortiz, Alejandro Ruiz-Argüelles, Manuel A Ruiz-Delgado, Rodrigo J Ruiz-Delgado, Guillermo Ruiz-Reyes, Manuel Priesca-Marín, Merari Starlight Torres-Priego, David Blumenkron-Marroquin, Guillermo J Ruiz-Delgado
BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217...
May 18, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28507026/lineage-specific-metabolic-properties-and-vulnerabilities-of-t-cells-in-the-demyelinating-central-nervous-system
#4
Scott M Seki, Max Stevenson, Abagail M Rosen, Sanja Arandjelovic, Lelisa Gemta, Timothy N J Bullock, Alban Gaultier
Multiple sclerosis (MS) is a disease that is characterized by immune-mediated destruction of CNS myelin. Current MS therapies aim to block peripheral immune cells from entering the CNS. Although these treatments limit new inflammatory activity in the CNS, no treatment effectively prevents long-term disease progression and disability accumulation in MS patients. One explanation for this paradox is that current therapies are ineffective at targeting immune responses already present in the CNS. To this end, we sought to understand the metabolic properties of T cells that mediate ongoing inflammation in the demyelinating CNS...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28507011/influence-of-diet-in-multiple-sclerosis-a-systematic-review
#5
REVIEW
M José Bagur, M Antonia Murcia, Antonia M Jiménez-Monreal, Josep A Tur, M Mar Bibiloni, Gonzalo L Alonso, Magdalena Martínez-Tomé
Nutrition is considered to be a possible factor in the pathogenesis of the neurological disease multiple sclerosis (MS). Nutrition intervention studies suggest that diet may be considered as a complementary treatment to control the progression of the disease; a systematic review of the literature on the influence of diet on MS was therefore conducted. The literature search was conducted by using Medlars Online International Literature (MEDLINE) via PubMed and Scopus. Forty-seven articles met the inclusion criteria...
May 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28498568/reconstitution-of-immune-cell-populations-in-multiple-sclerosis-patients-after-autologous-stem-cell-transplantation
#6
REVIEW
Fredrick G Karnell, Dongxia Lin, Samantha Motley, Thomas Duhen, Noha Lim, Daniel J Campbell, Laurence A Turka, Holden T Maecker, Kristina M Harris
Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. In a phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) hematopoietic stem cell transplant resulted in 69.2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new MRI lesions through year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post HSCT and the impact of treatment on the phenotype of circulating T cells in this study population...
May 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28497440/-treatment-of-relapsing-remitting-multiple-sclerosis-with-fingolimod-in-routine-clinical-practice
#7
C Alcala-Vicente, F C Perez-Miralles, F Gascon-Gimenez, I Bosca-Blasco, A Navarre-Gimeno, F Coret-Ferrer, B Casanova-Estruch
INTRODUCTION: Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. AIM: To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. PATIENTS AND METHODS: We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014...
May 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28481159/characterization-of-annual-disease-progression-of-multiple-sclerosis-patients-a-population-based-study
#8
Jonatan Freilich, Ali Manouchehrinia, Mark Trusheim, Lynn G Baird, Sophie Desbiens, Ernst Berndt, Jan Hillert
BACKGROUND: Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching the milestone. OBJECTIVE: To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS)...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28480777/how-far-away-from-having-an-effective-treatment-option-for-progressive-multiple-sclerosis-are-we
#9
Arianna Sartori, Jacopo Fantini, Paolo Manganotti
No abstract text is available yet for this article.
May 8, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28468939/modelling-amyotrophic-lateral-sclerosis-progress-and-possibilities
#10
REVIEW
Philip Van Damme, Wim Robberecht, Ludo Van Den Bosch
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects the motor system and presents with progressive muscle weakness. Most patients survive for only 2-5 years after disease onset, often due to failure of the respiratory muscles. ALS is a familial disease in ∼10% of patients, with the remaining 90% developing sporadic ALS. Over the past decade, major advances have been made in our understanding of the genetics and neuropathology of ALS. To date, around 20 genes are associated with ALS, with the most common causes of typical ALS associated with mutations in SOD1, TARDBP, FUS and C9orf72 Advances in our understanding of the genetic basis of ALS have led to the creation of different models of this disease...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28468254/natalizumab-in-multiple-sclerosis-long-term-management
#11
REVIEW
Marinella Clerico, Carlo Alberto Artusi, Alessandra Di Liberto, Simona Rolla, Valentina Bardina, Pierangelo Barbero, Stefania Federica De Mercanti, Luca Durelli
Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses...
April 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28467798/mechanism-of-oxidative-stress-p38mapk-sgk1-signaling-axis-in-experimental-autoimmune-encephalomyelitis-eae
#12
Liang Wang, Bin Li, Mo-Yuan Quan, Lin Li, Yuan Chen, Guo-Jun Tan, Jing Zhang, Xiao-Peng Liu, Li Guo
BACKGROUND: Multiple sclerosis (MS), a complex disease associated with multifocal demyelination of the central nervous system and poorly understood etiology. It has been previously indicated that many factors, including oxidative stress and p38MAPK-SGK1 pathway, contribute to the pathogenesis of MS. METHODS: This study, using an experimental autoimmune encephalomyelitis (EAE) model system, was aimed at investigating the molecular mechanisms determining interaction p38MAPK-SGK1 pathway and oxidative stress in MS pathogenesis...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466274/neural-stem-cell-based-regenerative-approaches-for-the-treatment-of-multiple-sclerosis
#13
REVIEW
Juan Xiao, Rongbing Yang, Sangita Biswas, Yunhua Zhu, Xin Qin, Min Zhang, Lihong Zhai, Yi Luo, Xiaoming He, Chun Mao, Wenbin Deng
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, and demyelinating disorder of the central nervous system (CNS), which ultimately leads to axonal loss and permanent neurological disability. Current treatments for MS are largely comprised of medications that are either immunomodulatory or immunosuppressive and are aimed at reducing the frequency and intensity of relapses. Neural stem cells (NSCs) in the adult brain can differentiate into oligodendrocytes in a context-specific manner and are shown to be involved in the remyelination in these patients...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28458007/probing-the-inhibitory-activity-of-epigallocatechin-gallate-on-toxic-aggregates-of-mutant-l84f-sod1-protein-through-geometry-based-sampling-and-steered-molecular-dynamics
#14
E Srinivasan, R Rajasekaran
Amyloid formation and protein aggregation are considered to be at the core of the disease pathology for the various neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS). Considerable experimental reports have suggested that epigallocatechin-gallate (EGCG), a natural polyphenol from the green tea inhibits the amyloid formation in multiple neurodegenerative disease. Mutations in SOD1 protein are considered to a key factor that contributes towards the rapid disease progression and the pathogenesis in both, the sporadic and familial form...
April 20, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28455383/autologous-hematopoietic-stem-cell-transplantation-in-multiple-sclerosis-a-meta-analysis
#15
Maria Pia Sormani, Paolo A Muraro, Irene Schiavetti, Alessio Signori, Alice Laroni, Riccardo Saccardi, Gian Luigi Mancardi
OBJECTIVE: To summarize the evidence on immunoablative therapy followed by autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and treatment-refractory multiple sclerosis (MS). METHODS: We collected all the published studies of aHSCT in any form of MS from 1995 to 2016, carefully excluding reports that were updated in subsequent studies. Endpoints were transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status...
April 28, 2017: Neurology
https://www.readbyqxmd.com/read/28454993/frameless-stereotactic-radiosurgery-for-the-treatment-of-multiple-sclerosis-related-trigeminal-neuralgia
#16
Alfredo Conti, Antonio Pontoriero, Giuseppe Iatì, Felice Esposito, Enrico Nastro Siniscalchi, Salvatore Crimi, Sergio Vinci, Anna Brogna, Francesco De Ponte, Antonino Germanò, Stefano Pergolizzi, Francesco Tomasello
BACKGROUND: Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The non-isocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. METHODS: Twenty-seven patients with refractory TN and MS were treated...
April 25, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28453541/the-real-world-effectiveness-and-safety-of-fingolimod-in-relapsing-remitting-multiple-sclerosis-patients-an-observational-study
#17
Guillermo Izquierdo, Fátima Damas, Maria Dolores Páramo, Juan Luis Ruiz-Peña, Guillermo Navarro
Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28451391/follow-up-of-multiple-sclerosis-patients-treated-with-endotherapia-gemsp
#18
Michel Geffard, Arturo Mangas, Rafael Coveñas
Endotherapia (GEMSP) is a novel therapeutic approach for multiple sclerosis (MS). The aim of the present study was to demonstrate the efficiency of Endotherapia in the follow-up of 193 patients with MS. The efficiency coefficient that was evaluated was the Expanded Disability Status Scale (EDSS) score, which is a functional scale of MS progression. The evaluated score of each patient during follow-up visits was compared with the theoretical score of the disease progression without GEMSP. The evolution of the EDSS score was evaluated according to the inclusion score...
March 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28450894/peginterferon-beta-1a-reduces-disability-worsening-in-relapsing-remitting-multiple-sclerosis-2-year-results-from-advance
#19
Scott D Newsome, Bernd C Kieseier, Shifang Liu, Xiaojun You, Elizabeth Kinter, Serena Hung, Bjoern Sperling
BACKGROUND: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing-remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL). METHODS: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks...
January 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28445498/metabolic-profiles-by-1h-magnetic-resonance-spectroscopy-in-natalizumab-associated-post-pml-lesions-of-multiple-sclerosis-patients-who-survived-progressive-multifocal-leukoencephalopathy-pml
#20
Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Eva-Maria Kolb, Gisa Ellrichmann, Aiden Haghikia, Ralf Gold, Carsten Lukas
PURPOSE: Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using 1H-magnetic resonance spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status...
2017: PloS One
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