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Dimethyl fumarate

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https://www.readbyqxmd.com/read/28537110/three-year-clinical-outcomes-of-relapsing-multiple-sclerosis-patients-treated-with-dimethyl-fumarate-in-a-united-states-community-health-center
#1
Kyle Smoot, Kateri J Spinelli, Tamela Stuchiner, Lindsay Lucas, Chiayi Chen, Lois Grote, Elizabeth Baraban, Kiren Kresa-Reahl, Stanley Cohan
BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#2
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28530523/cost-effectiveness-of-peginterferon-beta-1a-and-alemtuzumab-in-relapsing-remitting-multiple-sclerosis
#3
Ankur A Dashputre, Khalid M Kamal, Gauri Pawar
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28506000/therapeutic-effects-of-oral-dimethyl-fumarate-on-stroke-induced-by-middle-cerebral-artery-occlusion-an-animal-experimental-study
#4
Anahid Safari, Mehdi Fazeli, Mohammad Reza Namavar, Nader Tanideh, Peyman Jafari, Afshin Borhani-Haghighi
BACKGROUND: Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective characteristics that can be used for treatment of acute ischemic stroke. OBJECTIVE: To investigate the therapeutic effects of DMF on histological and functional recovery of rats after transient middle cerebral artery (MCA) occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were randomized into three groups by block randomization. In the sham group (n = 7), the neck was opened, but neither MCA was occluded, nor any drug was administered...
May 9, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28491903/dimethyl-fumarate-alters-b-cell-memory-and-cytokine-production-in-ms-patients
#5
Matthew D Smith, Kyle A Martin, Peter A Calabresi, Pavan Bhargava
We evaluated the effect of dimethyl fumarate (DMF) treatment on B-cell memory and cytokine production in 18 patients with relapsing remitting multiple sclerosis (RRMS) using peripheral blood mononuclear cells obtained prior to and at 6 months post-DMF initiation. We noted a decline in the absolute B-cell number with DMF treatment, with a preferential depletion of memory B cells and a concurrent increase in naïve B cells. We noted significant reductions in GM-CSF, TNF-α, and IL-6 producing B cells with DMF treatment...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28480794/dimethyl-fumarate-induces-changes-in-b-and-t-lymphocyte-function-independent-of-the-effects-on-absolute-lymphocyte-count
#6
Erin E Longbrake, Claudia Cantoni, Salim Chahin, Francesca Cignarella, Anne H Cross, Laura Piccio
BACKGROUND: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. OBJECTIVES: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28465407/role-of-nrf2-signaling-in-the-regulation-of-vascular-bk-channel-beta-1-subunit-expression-and-bk-channel-function-in-high-fat-diet-induced-diabetic-mice
#7
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channel β1 subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high fat diet (HFD)-induced obese/diabetic mice...
May 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28460056/dimethyl-fumarate-mediates-nrf2-dependent-mitochondrial-biogenesis-in-mice-and-humans
#8
Genki Hayashi, Mittal Jasoliya, Francesco Saccà, Chiara Pane, Alessandro Filla, Angela Marsili, Giorgia Puorro, Roberta Lanzillo, Vincenzo Brescia Morra, Gino Cortopassi
The induction of mitochondrial biogenesis could potentially alleviate mitochondrial and muscle disease. We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in in vitro, and also dosed in vivo to mice and humans. The induction of mitochondrial gene expression is more dependent on its target Nrf2 than hydroxycarboxylic acid receptor 2 (HCAR2). Thus, DMF induces mitochondrial biogenesis primarily through its action on Nrf2, and is the first drug demonstrated to increase mitochondrial biogenesis with in vivo human dosing...
April 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28440858/treatment-with-disease-modifying-drugs-for-people-with-a-first-clinical-attack-suggestive-of-multiple-sclerosis
#9
REVIEW
Graziella Filippini, Cinzia Del Giovane, Marinella Clerico, Omid Beiki, Miriam Mattoscio, Federico Piazza, Sten Fredrikson, Irene Tramacere, Antonio Scalfari, Georgia Salanti
BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28436295/treatment-response-to-dimethyl-fumarate-is-characterized-by-disproportionate-cd8-t-cell-reduction-in-ms
#10
Vinzenz Fleischer, Michaela Friedrich, Ayman Rezk, Ulrike Bühler, Esther Witsch, Timo Uphaus, Stefan Bittner, Sergiu Groppa, Björn Tackenberg, Amit Bar-Or, Frauke Zipp, Felix Luessi
BACKGROUND: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). OBJECTIVE: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. METHODS: Peripheral blood lymphocyte subsets were analyzed by flow cytometry...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#11
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28412473/nanoformulations-for-dimethyl-fumarate-physicochemical-characterization-and-in-vitro-in-vivo-behavior
#12
Elisabetta Esposito, Rita Cortesi, Markus Drechsler, Jie Fan, Bingmei M Fu, Laura Calderan, Silvia Mannucci, Federico Boschi, Claudio Nastruzzi
Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple sclerosis treatment (Tecfidera®). Nevertheless, since Tecfidera® capsules induce flushing, gastro-intestinal events and other more serious drawbacks, in this investigation a nanoparticle based system to be administered by an alternative way is proposed. In particular this study describes the preparation and characterization of dimethyl fumarate-containing solid lipid nanoparticles (SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80 and cationic SLN constituted of tristearin in mixture with dimethyldioctadecylammonium chloride were investigated...
April 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28408330/muscarinic-cholinoreceptors-m1-m2-m3-and-m4-type-modulate-the-acetylcholine-secretion-in-the-frog-neuromuscular-junction
#13
Andrei N Tsentsevitsky, Irina V Kovyazina, Leniz F Nurullin, Eugeny E Nikolsky
Muscarinic cholinoreceptors regulate the neurosecretion process in vertebrate neuromuscular junctions. The diversity of muscarinic effects on acetylcholine (ACh) secretion may be attributed to the different muscarinic subtypes involved in this process. In the present study, the location of five muscarinic receptor subtypes (M1, M2, M3, M4 and M5) on the motor nerve terminals of frog cutaneous pectoris muscle was shown using specific polyclonal antibodies. The modulatory roles of these receptors were investigated via assessment of the effects of muscarine and specific muscarinic antagonists on the quantal content of endplate currents (EPCs) and the time course of secretion, which was estimated from the distribution of "real" synaptic delays of EPCs recorded in a low Ca(2+)/high Mg(2+) solution...
April 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28396093/what-s-new-about-oral-treatments-in-multiple-sclerosis-immunogenetics-still-under-question
#14
REVIEW
Cristiana Pistono, Cecilia Osera, Chiara Boiocchi, Giulia Mallucci, Mariaclara Cuccia, Roberto Bergamaschi, Alessia Pascale
Multiple Sclerosis (MS) is a chronic pathology affecting the Central Nervous System characterized by inflammatory processes that lead to demyelination and neurodegeneration. In MS treatment, disease modifying therapies (DMTs) are essential to reduce disease progression by suppressing the inflammatory response responsible for promoting lesion formation. Recently, in addition to the classical injectable DMTs like Interferons and Glatiramer acetate, new orally administered drugs have been approved for MS therapy: dimethyl fumarate, teriflunomide and fingolimod...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28391741/unexpected-exacerbations-following-initiation-of-disease-modifying-drugs-in-neuromyelitis-optica-spectrum-disorder-which-factor-is-responsible-anti-aquaporin-4-antibodies-b-cells-th1-cells-th2-cells-th17-cells-or-others
#15
Jun-Ichi Kira
Some disease-modifying drugs for multiple sclerosis, which mainly act on T cells, are ineffective for neuromyelitis optica spectrum disorder and induce unexpected relapses. These include interferon beta, glatiramer acetate, fingolimod, natalizumab, and alemtuzumab. The cases reported here suggest that dimethyl fumarate, which reduces the number of Th1 and Th17 cells and induces IL-4-producing Th2 cells, is also unsuitable for neuromyelitis optica spectrum disorder, irrespective of anti-aquaporin 4 IgG serostatus...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28391740/catastrophic-relapses-following-initiation-of-dimethyl-fumarate-in-two-patients-with-neuromyelitis-optica-spectrum-disorder
#16
Bassem I Yamout, Shawkat Beaini, Maya M Zeineddine, Nabil Akkawi
We report two cases of neuromyelitis optica spectrum disorder (NMOSD) who were misdiagnosed as multiple sclerosis (MS) and developed catastrophic relapses following initiation of dimethyl fumarate. Both patients developed a severe myelitis extending from the cervical cord to the medulla with significant cord swelling, resulting in complete quadriplegia and respiratory difficulties, in addition to severe bilateral visual loss in one patient. It is of note that both catastrophic relapses occurred 2 and 3 months following initiation of dimethyl fumarate...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28390814/meeting-report-of-the-pathogenesis-of-pemphigus-and-pemphigoid-meeting-in-munich-september-2016
#17
Enno Schmidt, Volker Spindler, Rüdiger Eming, Masayuki Amagai, Frank Antonicelli, John F Baines, Meriem Belheouane, Philippe Bernard, Luca Borradori, Marzia Caproni, Giovanni Di Zenzo, Sergei Grando, Karen Harman, Marcel F Jonkman, Hiroshi Koga, Ralf J Ludwig, Andrew P Kowalczyk, Eliane J Müller, Wataru Nishie, Hendri Pas, Aimee S Payne, Christian D Sadik, Allan Seppänen, Jane Setterfield, Hiroshi Shimizu, Animesh A Sinha, Eli Sprecher, Michael Sticherling, Hideyuki Ujiie, Detlef Zillikens, Michael Hertl, Jens Waschke
Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases...
April 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28382685/dimethyl-fumarate-ameliorates-myoclonus-stemming-from-protein-misfolding-in-oligodendrocytes
#18
Cherie M Southwood, Danielle M Garshott, Chelsea R Richardson, Navid Seraji-Bozorgzad, Andrew M Fribley, Alexander Gow
Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials' data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre-clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology...
April 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28377940/dimethyl-fumarate-induced-lymphopenia-in-ms-due-to-differential-t-cell-subset-apoptosis
#19
Mahtab Ghadiri, Ayman Rezk, Rui Li, Ashley Evans, Felix Luessi, Frauke Zipp, Paul S Giacomini, Jack Antel, Amit Bar-Or
OBJECTIVE: To examine the mechanism underlying the preferential CD8(+) vs CD4(+) T-cell lymphopenia induced by dimethyl fumarate (DMF) treatment of MS. METHODS: Total lymphocyte counts and comprehensive T-cell subset analyses were performed in high-quality samples obtained from patients with MS prior to and serially following DMF treatment initiation. Random coefficient mixed-effects analysis was used to model the trajectory of T-cell subset losses in vivo. Survival and apoptosis of distinct T-cell subsets were assessed following in vitro exposure to DMF...
May 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28370349/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-antioxidant-response-promotes-melanocyte-viability-and-reduces-toxicity-of-the-vitiligo-inducing-phenol-monobenzone
#20
Omotayo A Arowojolu, Seth J Orlow, Nada Elbuluk, Prashiela Manga
Vitiligo, characterized by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterized. We hypothesized that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity...
March 31, 2017: Experimental Dermatology
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