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Neda Djedović, Suzana Stanisavljevic, Bojan Jevtić, Miljana Momčilović, Irena Lavrnja, Djordje Miljković
Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Frank R Ernst, Peri Barr, Riad Elmor, Schiffon L Wong
OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF...
December 2017: Current Medical Research and Opinion
Tetsuo Toyama, Agnieszka P Looney, Brendon M Baker, Lukasz Stawski, Paul Haines, Robert Simms, Aleksander D Szymaniak, Xaralabos Varelas, Maria Trojanowska
Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatment options. Fumaric acid esters, including dimethyl fumarate (DMF, Tecfidera; Biogen, Cambridge, MA), have shown therapeutic effects in several disease models, prompting us to determine whether DMF is effective as a treatment for SSc dermal fibrosis. We found that DMF blocks the profibrotic effects of transforming growth factor-β (TGFβ) in SSc skin fibroblasts. Mechanistically, we found that DMF treatment reduced nuclear localization of transcriptional coactivator with PDZ binding motif (TAZ) and Yes-associated protein (YAP) proteins via inhibition of the phosphatidylinositol 3 kinase/protein kinase B (Akt) pathway...
January 2018: Journal of Investigative Dermatology
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...
June 2017: European Journal of Pharmaceutics and Biopharmaceutics
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2017: Nature Biotechnology
Qi Wu, Qin Wang, Guangmei Mao, Catherine A Dowling, Steven K Lundy, Yang Mao-Draayer
Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4-6 and 18-26 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Danilo Di Bona, Marcello Albanesi, Lucia A Giliberti, Andrea Nico, Maria Pia Rossi, Maria Filomena Caiaffa, Luigi Macchia
No abstract text is available yet for this article.
May 2017: Journal of Allergy and Clinical Immunology in Practice
Tiffany Shih, Craig Wakeford, Dennis Meletiche, Jesse Sussell, Adrienne Chung, Yanmei Liu, Jin Joo Shim, Darius Lakdawalla
OBJECTIVES: To illustrate a more comprehensive view of value associated with medicines treating a highly severe illness and to apply these insights to estimate the costs and benefits of 3 treatments for multiple sclerosis (MS): Avonex, Tysabri, and Tecfidera. STUDY DESIGN: Retrospective study spanning 2002 to 2013. We used economic theory to derive the value of therapy to patients with MS and to individuals who face the risk of contracting MS in the future, under the alternative assumptions that therapies were fully insured or paid for out of pocket...
November 1, 2016: American Journal of Managed Care
Matthew A J Duncton, Rajinder Singh
A one-pot and scalable synthesis of tetrazolones (tetrazol-5-ones) from acid chlorides using azidotrimethylsilane is presented. The reaction tolerates many functional groups and can furnish aryl-, heteroaryl-, alkenyl-, or alkyl-substituted tetrazolone products in moderate to excellent yield (14-94%). No reduction in yield was observed when the reaction was undertaken on a larger-scale (20-36 g). The method could be used for the late-stage functionalization of pharmaceuticals, to provide tetrazolone congeners of the marketed drugs aspirin, indomethacin, probenecid, telmisartan, bexarotene, niacin (vitamin B3), and the active metabolite of the recently-launched immuno-modulatory agent, BG-12 (Tecfidera® )...
October 4, 2016: Organic & Biomolecular Chemistry
Laurence Booth, Mark Malkin, Paul Dent
No abstract text is available yet for this article.
July 2016: Aging
Manuj Ahuja, Navneet Ammal Kaidery, Lichuan Yang, Noel Calingasan, Natalya Smirnova, Arsen Gaisin, Irina N Gaisina, Irina Gazaryan, Dmitry M Hushpulian, Ismail Kaddour-Djebbar, Wendy B Bollag, John C Morgan, Rajiv R Ratan, Anatoly A Starkov, M Flint Beal, Bobby Thomas
UNLABELLED: A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
D Smith
BACKGROUND: Psoriasis is a chronic skin disease associated with increased morbidity and mortality. Effective and safe long term treatment options are required to manage the illness successfully. A number of systemic agents are available, however, each of them has potentially significant side effects. Fumaric acid esters (FAE) are used first line in Germany for the management of moderate to severe psoriasis, however, their use in Ireland is on an unlicensed basis (Clinical and Experimental Dermatology 37:786-801, 2012)...
February 2017: Irish Journal of Medical Science
Ulf Schulze-Topphoff, Michel Varrin-Doyer, Kara Pekarek, Collin M Spencer, Aparna Shetty, Sharon A Sagan, Bruce A C Cree, Raymond A Sobel, Brian T Wipke, Lawrence Steinman, Robert H Scannevin, Scott S Zamvil
Dimethyl fumarate (DMF) (BG-12, Tecfidera) is a fumaric acid ester (FAE) that was advanced as a multiple sclerosis (MS) therapy largely for potential neuroprotection as it was recognized that FAEs are capable of activating the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, DMF treatment in randomized controlled MS trials was associated with marked reductions in relapse rate and development of active brain MRI lesions, measures considered to reflect CNS inflammation...
April 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
Steven K Lundy, Qi Wu, Qin Wang, Catherine A Dowling, Sophina H Taitano, Guangmei Mao, Yang Mao-Draayer
OBJECTIVE: To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4-6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)-10 by RRMS patient B cells was also analyzed. RESULTS: Total numbers of peripheral blood B lymphocytes declined after 4-6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27(neg) B-cell subsets...
April 2016: Neurology® Neuroimmunology & Neuroinflammation
Catharina C Gross, Andreas Schulte-Mecklenbeck, Svenja Klinsing, Anita Posevitz-Fejfár, Heinz Wiendl, Luisa Klotz
OBJECTIVE: To evaluate the effect of dimethyl fumarate (DMF; Tecfidera, Biogen, Weston, MA) on CD4(+) and CD8(+) T cell subsets in patients with multiple sclerosis (MS). METHODS: Peripheral lymphocyte subsets, including CD4(+) and CD8(+) memory cells and T helper (TH) cells TH1, TH2, TH17, and peripheral regulatory T cell (pTreg) subpopulations were analyzed before and 6 months after onset of DMF treatment. RESULTS: CD4(+) and CD8(+) memory T cells were preferentially decreased compared to naive CD4(+) and CD8(+) T cell populations...
February 2016: Neurology® Neuroimmunology & Neuroinflammation
Emma D Deeks
Dimethyl fumarate (Tecfidera(®)) is an oral disease-modifying agent indicated for the twice-daily treatment of relapsing forms of multiple sclerosis (MS) and relapsing-remitting MS (RRMS). It displays immunomodulating and neuroprotective properties, both of which may contribute to its efficacy in these settings. In two phase III trials of 2 years' duration (DEFINE and CONFIRM), twice-daily dimethyl fumarate reduced clinical relapse (both the proportion of patients with MS relapse and the annualized relapse rate), as well as MRI measures of disease activity, versus placebo in adults with RRMS; the drug also reduced disability progression relative to placebo in one of the two studies (DEFINE)...
February 2016: Drugs
Jeroen Van Schependom, Jeroen Gielen, Jorne Laton, Guy Nagels
Recently, three progressive multifocal leukoencephalopathy (PML) cases have been reported in multiple sclerosis (MS) patients, two treated with fingolimod (Gilenya, Novartis), the third with dimethyl fumarate (Tecfidera, Biogen). Because our immunotherapeutic arsenal in MS and other diseases is increasing, and because PML is a very serious health risk, it is of interest to the clinical community to show how we can assess this risk in a statistically sound way. The null-hypothesis for this analysis was that there is no elevated risk for PML in patients treated with one of these recent drugs, compared to the incidence in the general population...
March 2016: Multiple Sclerosis: Clinical and Laboratory Research
Bhupendra O Khatri, Jeffery Garland, Joseph Berger, John Kramer, Lisa Sershon, Tayo Olapo, Jean Sesing, Mary Dukic, Eileen Rehn
Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). Our study suggests that this drug may have immunosuppressive properties evidenced by significant sustained reduction in CD8 lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This observation is relevant in light of the recent case of progressive multifocal leukoencephalopathy in a patient receiving this drug.
July 2015: Multiple Sclerosis and related Disorders
Qin Wang, Sergei Chuikov, Sophina Taitano, Qi Wu, Arjun Rastogi, Samuel J Tuck, Joseph M Corey, Steven K Lundy, Yang Mao-Draayer
Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood...
2015: International Journal of Molecular Sciences
Siddharama Pawate, Francesca Bagnato
BACKGROUND: Multiple sclerosis (MS) is the most common cause of nontraumatic neurological disability in young adults. There is great need for developing effective treatments to arrest the disease. As of today, there is no cure for MS but several agents mitigating its effects are available. The era of disease-modifying therapy began with the use of interferon beta and glatiramer acetate in the 1990s. Given the injectable nature and the limited efficacy of these agents, efforts are ongoing to develop new treatments...
April 2015: Neurologist
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