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https://www.readbyqxmd.com/read/28302022/glial-cell-a-potential-target-for-cellular-and-drug-based-therapy-in-various-cns-diseases
#1
Shakeeb Ahmed, Yasmin Sultana, Azka Gull, Tahir Khuroo, Mohd Aqil
Glial cells are integrated part of neurovascular unit of blood brain barrier (BBB). They undergo mitosis and mainly classified as astrocytes, oligodendrocytes, microglia, ependymal cells and nerve glial antigen 2 cells. Being a most versatile glial cell, astrocytes provide structural support to neurons, maintain brain homeostasis, take part in neuronal communication, and perform some housekeeping functions. Oligodendrocytes myelinate the neuronal axons for proper transmission of nerve impulse and microglia are brain immune cells...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28300418/incurred-sample-reanalysis-of-fingolimod-and-fingolimod-phosphate-in-blood-stability-evaluation-and-application-to-a-rat-pharmacokinetic-study
#2
Ramakrishna Nirogi, Nagasurya Prakash Padala, Devender Reddy Ajjala, Rajesh Kumar Boggavarapu, Praveen Kunduru
BACKGROUND: Incurred sample reanalysis (ISR) is an in-study validation parameter, which reinforces that the validated bioanalytical methods are reproducible. ISR of whole blood samples is complex when the test compounds can interconvert, ex vivo. Fingolimod and fingolimod phosphate are highly distributed in the blood cellular components and undergo rapid interconversion, both in vivo and ex vivo. An LC-MS/MS method capable of simultaneous quantification of fingolimod and fingolimod phosphate with the controlled sample preparation procedure is essential...
March 16, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28299825/fingolimod-gilenya-%C3%A2-in-multiple-sclerosis-bradycardia-atrioventricular-blocks-and-mild-effect-on-the-qtc-interval-something-to-do-with-the-l-type-calcium-channel
#3
Sylvie Pilote, Chantale Simard, Benoit Drolet
Cardiac arrhythmias and ECG abnormalities including bradycardia, prolongation of the QT interval and atrioventricular (AV) conduction blocks have been extensively observed with fingolimod, the first marketed oral drug for treating the relapsing-remitting form of multiple sclerosis. The present study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels; 1) in vitro, 2) ex vivo and 3) in vivo. 1) Patch-clamp experiments in whole cell configuration were performed on Cav 1...
March 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28294696/cerebrospinal-fluid-mtdna-concentration-is-elevated-in-multiple-sclerosis-disease-and-responds-to-treatment
#4
Cyra E Leurs, Petar Podlesniy, Ramon Trullas, Lisanne Balk, Martijn D Steenwijk, Arjan Malekzadeh, Fredrik Piehl, Bernard Mj Uitdehaag, Joep Killestein, Jack van Horssen, C E Teunissen
BACKGROUND: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. OBJECTIVES: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28283486/systematic-literature-review-and-network-meta-analysis-in-highly-active-relapsing-remitting-multiple-sclerosis-and-rapidly-evolving-severe-multiple-sclerosis
#5
Eline Huisman, Katerina Papadimitropoulou, James Jarrett, Matthew Bending, Zoe Firth, Felicity Allen, Nick Adlard
OBJECTIVE: Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS. METHODS: A systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS...
March 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28283109/classifying-pml-risk-with-disease-modifying-therapies
#6
REVIEW
Joseph R Berger
OBJECTIVE: To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). BACKGROUND: All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28279838/modulation-of-sphingosine-1-phosphate-in-inflammatory-bowel-disease
#7
REVIEW
Laurent Peyrin-Biroulet, Ronald Christopher, Dominic Behan, Cheryl Lassen
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, involve an inappropriate immune reaction in the digestive tract, causing a variety of disabling symptoms. The advent of monoclonal antibodies (anti-tumor necrosis factor, anti-integrin, anti-interleukin -23) has revolutionized IBD management. Nevertheless, these agents, with potential for immunogenicity, are associated with high rates of response loss and disease relapse over time. They are also associated with high production costs...
March 6, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28273776/half-dose-fingolimod-for-treating-relapsing-remitting-multiple-sclerosis-observational-study
#8
Chiara Zecca, Arianna Merlini, Giulio Disanto, Mariaemma Rodegher, Letizia Panicari, Marzia Anita Lucia Romeo, Ursula Candrian, Maria Josè Messina, Emanuele Pravatà, Lucia Moiola, Catia Stefanin, Angelo Ghezzi, Patrizia Perrone, Francesco Patti, Giancarlo Comi, Claudio Gobbi, Vittorio Martinelli
OBJECTIVES: To investigate the efficacy and safety of fingolimod (FTY) 0.5 mg administered every other day (FTY-EOD) compared to every day (FTY-ED) in multiple sclerosis patients. METHODS: Multicentre retrospective observational study. Clinical, laboratory and neuroimaging data were consecutively collected from 60 FTY-EOD and 63 FTY-ED patients. Baseline characteristics were compared using logistic regression. Efficacy in preventing occurrence of relapses and demyelinating lesions was tested using propensity score-adjusted Cox and linear regressions...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273765/comment-on-extensive-white-matter-lesions-after-2-years-of-fingolimod-progressive-multifocal-leukoencephalopathy-or-ms-relapse
#9
María Inés Gaitán, Jorge Correale
No abstract text is available yet for this article.
April 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273764/extensive-white-matter-lesions-after-2%C3%A2-years-of-fingolimod-progressive-multifocal-leukoencephalopathy-or-ms-relapse
#10
Marine Boudot de la Motte, Céline Louapre, Anne Bertrand, Pauline Reach, Catherine Lubetzki, Caroline Papeix, Elisabeth Maillart
BACKGROUND: Fingolimod is a widely used treatment for highly active relapsing-remitting multiple sclerosis. OBJECTIVES: To describe the case of a 27-year-old patient treated for more than 2 years by Fingolimod, who presented hemiplegia and speech disturbances associated with extensive white matter lesions on brain magnetic resonance imaging (MRI). METHODS: Case study. RESULTS: Although initial presentation questioned the possibility of progressive multifocal leukoencephalopathy, final diagnosis was multiple sclerosis (MS) relapse...
April 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273762/natural-killer-cell-subpopulations-are-associated-with-mri-activity-in-a-relapsing-remitting-multiple-sclerosis-patient-cohort-from-australia
#11
P Caruana, K Lemmert, K Ribbons, R Lea, J Lechner-Scott
BACKGROUND: The importance of the innate immune system in multiple sclerosis (MS) is increasingly recognized and the role of natural killer (NK) cells in controlling autoimmunity may be an important modulator of disease activity. OBJECTIVE: To examine NK subsets in MS patients on different treatments and to evaluate the role of NK subsets as indicators for disease activity. METHODS: We measured NK subset levels in blood obtained from 110 relapsing-remitting MS patients...
November 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273090/fingolimod-effects-in-neuroinflammation-regulation-of-astroglial-glutamate-transporters
#12
De-Hyung Lee, Silvia Seubert, Konstantin Huhn, Lukas Brecht, Caroline Rötger, Anne Waschbisch, Johannes Schlachetzki, Alice Klausmeyer, Arthur Melms, Stefan Wiese, Jürgen Winkler, Ralf A Linker
Fingolimod is an oral sphingosine-1-phosphate-receptor modulator which reduces the recirculation of immune cells and may also directly target glial cells. Here we investigate effects of fingolimod on expression of astroglial glutamate transporters under pro-inflammatory conditions. In astrocyte cell culture, the addition of pro-inflammatory cytokines led to a significant downregulation of glutamate transporters glutamate transporter-1 (slc1a2/SLC1A2) and glutamate aspartate transporter (slc1a3/SLC1A3) expression on the mRNA or protein level...
2017: PloS One
https://www.readbyqxmd.com/read/28247239/effect-of-fingolimod-on-brain-volume-loss-in-patients-with-multiple-sclerosis
#13
REVIEW
Nicola De Stefano, Diego G Silva, Michael H Barnett
Brain atrophy occurs at a faster rate in patients with multiple sclerosis (MS) than in healthy individuals. In three randomized, controlled, phase III trials, fingolimod reduced the annual rate of brain volume loss (BVL) in patients with relapsing MS (RMS) by approximately one-third relative to that in individuals receiving placebo or intramuscular interferon beta-1a. Analysis of brain volume changes during study extensions has shown that this reduced rate of BVL is sustained in patients with RMS receiving fingolimod continuously...
February 28, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28245526/progressive-multifocal-leukoencephalopathy-driven-from-rarity-to-clinical-mainstream-by-iatrogenic-immunodeficiency
#14
REVIEW
Siraj A Misbah
Advances in immune-mediated targeted therapies have proven to be a double-edged sword for patients by highlighting the risk of iatrogenic infective complications. This has been exemplified by progressive multifocal leukoencephalopathy (PML), a hitherto rare devastating viral infection of the brain caused by the neurotropic JC polyoma virus. While PML achieved prominence during the first two decades of the HIV epidemic, effective anti-retroviral treatment and restitution of T cell function has led to PML being less prominent in this population...
February 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28240814/an-engineered-macroencapsulation-membrane-releasing-fty720-to-precondition-pancreatic-islet-transplantation
#15
Daniel T Bowers, Claire E Olingy, Preeti Chhabra, Linda Langman, Parker H Merrill, Ritu S Linhart, Michael L Tanes, Dan Lin, Kenneth L Brayman, Edward A Botchwey
Macroencapsulation is a powerful approach to increase the efficiency of extrahepatic pancreatic islet transplant. FTY720, a small molecule that activates signaling through sphingosine-1-phosphate receptors, is immunomodulatory and pro-angiogenic upon sustained delivery from biomaterials. While FTY720 (fingolimod, Gilenya) has been explored for organ transplantation, in the present work the effect of locally released FTY720 from novel nanofiber-based macroencapsulation membranes is explored for islet transplantation...
February 27, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28237728/recognition-of-viral-and-self-antigens-by-th1-and-th1-th17-central-memory-cells-in-patients-with-multiple-sclerosis-reveals-distinct-roles-in-immune-surveillance-and-relapses
#16
Moira Paroni, Virginia Maltese, Marco De Simone, Valeria Ranzani, Paola Larghi, Chiara Fenoglio, Anna M Pietroboni, Milena A De Riz, Maria C Crosti, Stefano Maglie, Monica Moro, Flavio Caprioli, Riccardo Rossi, Grazisa Rossetti, Daniela Galimberti, Massimiliano Pagani, Elio Scarpini, Sergio Abrignani, Jens Geginat
BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated. OBJECTIVE: We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS...
February 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#17
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28229120/leprosy-mimicking-basal-cell-carcinoma-in-a-patient-on-fingolimod
#18
Skylar Souyoul, Katharine Saussy, Barbara M Stryjewska, Elizabeth Grieshaber
No abstract text is available yet for this article.
January 2017: JAAD Case Reports
https://www.readbyqxmd.com/read/28218904/the-protumorigenic-potential-of-fty720-by-promoting-extramedullary-hematopoiesis-and-mdsc-accumulation
#19
Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, J C Morris, E N Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li, G Chen
FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28212923/multiple-sclerosis-in-the-real-world-a-systematic-review-of-fingolimod-as-a-case-study
#20
REVIEW
Tjalf Ziemssen, Jennie Medin, C Anne-Marie Couto, Catherine R Mitchell
INTRODUCTION: The aim of our study was to systematically review the growing body of published literature reporting on one specific multiple sclerosis (MS) treatment, fingolimod, in the real world to assess its effectiveness in patients with MS, evaluate methodologies used to investigate MS in clinical practice, and describe the evidence gaps for MS as exemplified by fingolimod. METHODS: We conducted a PRISMA-compliant systematic review of the literature (cut-off date: 4 March 2016)...
February 15, 2017: Autoimmunity Reviews
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