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Dimethyl fumarate

Sheena L Dupuy, Shahamat Tauhid, Shelley Hurwitz, Renxin Chu, Fawad Yousuf, Rohit Bakshi
INTRODUCTION: The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing-remitting (RR) MS. METHODS: We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1...
October 15, 2016: Neurology and Therapy
N Milanesi, G Bartolini, S Francalanci, M Gola
Dimethyl fumarate (DMF), the methyl ester form of fumaric acid (DMF) is an effective mold-growth inhibitor. It has a wide-spectrum biocide activity and has been used to protect leather during storage and transport. DMF was first identified as a potent contact sensitizer during a contact dermatitis outbreak that occurred because of its use in Chinese manufactured furniture (1,2). This article is protected by copyright. All rights reserved.
October 14, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Robert J Fox, Andrew Chan, Annie Zhang, James Xiao, Dane Levison, James B Lewin, Michael R Edwards, Jing L Marantz
Objective Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) and fingolimod are approved oral disease-modifying treatments for relapsing-remitting multiple sclerosis. In phase 3 trials, DMF (DEFINE/CONFIRM) and fingolimod (FREEDOMS/FREEDOMS II) resulted in significant reductions in clinical and magnetic resonance imaging activity, with acceptable safety profiles. Direct comparisons of these treatments are not possible due to a lack of head-to-head trials. We compared 2-year efficacy of DMF versus fingolimod at the approved dosage using a matching-adjusted indirect approach...
October 13, 2016: Current Medical Research and Opinion
Haiyan Peng, Huo Li, Adam Sheehy, Patrick Cullen, Norm Allaire, Robert H Scannevin
Delayed-release dimethyl fumarate (DMF) is an approved treatment for multiple sclerosis (MS). Microglia are considered central to MS pathophysiology, however the effects of DMF and the primary metabolite monomethyl fumarate (MMF) on microglia are not well characterized. We demonstrated that DMF and MMF altered transcriptional responses in primary microglia related to the nuclear factor (erythroid-derived 2)-like 2 pathway. Additionally, through an NRF2 independent manner, DMF, but not MMF significantly reduced production of proinflammatory mediators in classically activated microglia, and further rescued mitochondrial respiratory deficits in primary cortical neurons that were induced by activated microglia...
October 15, 2016: Journal of Neuroimmunology
Begoña M Escribano, Francisco J Medina-Fernández, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijoo, Fe I Garcia-Maceira, Rafael Lillo, Patricia Vieyra-Reyes, Ana I Giraldo, Evelio Luque, René Drucker-Colín, Isaac Túnez
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord...
October 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
Emanuele D'Amico, Aurora Zanghì, Carmela Leone, Hayrettin Tumani, Francesco Patti
Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so of JCV reactivation...
September 30, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Saskia M Leibowitz, Jun Yan
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways are involved in cell immune responses, apoptosis and infections. In multiple sclerosis (MS), NF-κB pathways are changed, leading to increased levels of NF-κB activation in cells. This may indicate a key role for NF-κB in MS pathogenesis. NF-κB signaling is complex, with many elements involved in its activation and regulation. Interestingly, current MS treatments are found to be directly or indirectly linked to NF-κB pathways and act to adjust the innate and adaptive immune system in patients...
2016: Frontiers in Molecular Neuroscience
Tara Nazareth, Howard S Friedman, Prakash Navaratnam, Denise A Herriott, John J Ko, Peri Barr, Rahul Sasane
BACKGROUND: In the US, the approved multiple sclerosis (MS) oral disease-modifying therapies (ODMTs) are fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF). FTY and TFN are recommended with once-daily doses with no up-titration, whereas DMF treatment is recommended twice-daily (BID) and is initiated with a 7-day starter dose of 120 mg BID before up-titration to the maintenance dose of 240 mg BID. Limited information exists regarding real-world ODMT prescribing patterns to aid physician/patient decision-making...
September 29, 2016: BMC Neurology
Emer Fogarty, Susanne Schmitz, Niall Tubridy, Cathal Walsh, Michael Barry
INTRODUCTION: Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. METHODS: A systematic review identified 28 randomised, placebo-controlled and direct comparative trials...
September 2016: Multiple Sclerosis and related Disorders
Jasna Jancic, Blazo Nikolic, Nikola Ivancevic, Vesna Djuric, Ivan Zaletel, Dejan Stevanovic, Sasa Peric, John N van den Anker, Janko Samardzic
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment...
September 17, 2016: Neurology and Therapy
Megan M Blewett, Jiji Xie, Balyn W Zaro, Keriann M Backus, Amnon Altman, John R Teijaro, Benjamin F Cravatt
Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear but may involve the covalent modification of proteins or DMF serving as a prodrug that is converted to monomethyl fumarate (MMF). We found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF sensitivity of >2400 cysteine residues in human T cells...
2016: Science Signaling
Yang Yao, Weimin Miao, Zhijia Liu, Wei Han, Kaibin Shi, Yi Shen, Handong Li, Qiang Liu, Ying Fu, DeRen Huang, Fu-Dong Shi
Oxidative stress plays an important role in cerebral ischemia-reperfusion injury. Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are antioxidant agents that can activate the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of antioxidant proteins. Here, we evaluated the impact of DMF and MMF on ischemia-induced brain injury and whether the Nrf2 pathway mediates the effects provided by DMF and MMF in cerebral ischemia-reperfusion injury...
December 2016: Translational Stroke Research
Moogeh Baharnoori, Jennifer Lyons, Akram Dastagir, Igor Koralnik, James M Stankiewicz
No abstract text is available yet for this article.
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Paul Wicks, Lawrence Rasouliyan, Bo Katic, Beenish Nafees, Emuella Flood, Rahul Sasané
BACKGROUND: Oral disease-modifying therapies offer equivalent or superior efficacy and greater convenience versus injectable options. OBJECTIVES: To compare patient-reported experiences of fingolimod and dimethyl fumarate. METHODS: Adult relapsing-remitting multiple sclerosis patients treated with fingolimod or dimethyl fumarate were recruited from an online patient community and completed an online survey about treatment side effects, discontinuation, and satisfaction...
2016: BMC Research Notes
Zhen-Gang Ma, Rui Ma, Xiao-Lin Xiao, Yong-Hui Zhang, Xin-Zi Zhang, Nan Hu, Jin-Lai Gao, Yu-Feng Zheng, De-Li Dong, Zhi-Jie Sun
UNLABELLED: Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activity on colon cancer cells. Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy...
October 15, 2016: Acta Biomaterialia
Diogo Mendes, Carlos Alves, Francisco Batel-Marques
OBJECTIVE: This study aimed to test the number needed to treat to benefit (NNTB) and to harm (NNTH), and the likelihood to be helped or harmed (LHH) when assessing benefits, risks, and benefit-risk ratios of disease-modifying treatments (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS). METHODS: In May 2016, we conducted a systematic review using the PubMed and Cochrane Central Register of Controlled Trials databases to identify phase III, randomized controlled trials with a duration of ≥2 years that assessed first-line (dimethyl fumarate [DMF], glatiramer acetate [GA], β-interferons [IFN], and teriflunomide) or second-line (alemtuzumab, fingolimod, and natalizumab) DMTs in patients with RRMS...
October 2016: CNS Drugs
Imran Khan, Shafi Ullah, Deog-Hwan Oh
The present study aims at in vitro antibacterial and antioxidant activity evaluation of chitosan modified with monomethyl fumaric acid (MFA) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as mediator. Three different kinds of chitosan derivatives Ch-Ds-1,Ch-Ds-2 and Ch-Ds-3 were synthesized by feeding different concentration of MFA. The chemical structures of resulting materials were characterized by (1)H NMR, (13)C NMR, HR-XRD, FT-IR and TNBS assay. The results showed that Ch-Ds-1, Ch-Ds-2 and Ch-Ds-3 were successfully synthesized...
November 5, 2016: Carbohydrate Polymers
U Mrowietz, J C Szepietowski, R Loewe, P Van de Kerkhof, R Lamarca, W G Ocker, V M Tebbs, I Pau-Charles
BACKGROUND: Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm(®) is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient. OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm(®) , in adults with moderate-to-severe chronic plaque psoriasis...
August 12, 2016: British Journal of Dermatology
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