scholarly journals Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

2020 ◽  
Vol 13 (10) ◽  
pp. 306 ◽  
Author(s):  
Stephanie Kourakis ◽  
Cara A. Timpani ◽  
Judy B. de Haan ◽  
Nuri Gueven ◽  
Dirk Fischer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dimethyl Fumarate ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Favourable Safety ◽  
Potential Benefits ◽  
Monomethyl Fumarate ◽  
Relapsing Remitting Multiple Sclerosis ◽  
And Oxidative Stress ◽  
Acid Esters

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

scholarly journals Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

2020 ◽  
Author(s):  
Stephanie Kourakis ◽  
Cara Timpani ◽  
Judy de Haan ◽  
Nuri Gueven ◽  
Dirk Fischer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dimethyl Fumarate ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Favourable Safety ◽  
Potential Benefits ◽  
Monomethyl Fumarate ◽  
Relapsing Remitting Multiple Sclerosis ◽  
And Oxidative Stress ◽  
Acid Esters

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

scholarly journals Dimethyl fumarate transfer into human milk

2020 ◽  
Vol 13 ◽  
pp. 175628642096841
Author(s):  
Andrea I. Ciplea ◽  
Palika Datta ◽  
Kathleen Rewers-Felkins ◽  
Teresa Baker ◽  
Ralf Gold ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Milk ◽  
Dimethyl Fumarate ◽  
Liquid Chromatography Mass Spectrometry ◽  
Primary Metabolite ◽  
Milk Samples ◽  
Relapsing Remitting ◽  
Infant Dose ◽  
Monomethyl Fumarate ◽  
Relapsing Remitting Multiple Sclerosis

Dimethyl fumarate (DMF) is approved for the treatment of relapsing-remitting multiple sclerosis. It is unknown whether DMF or its primary metabolite monomethyl fumarate (MMF) are excreted into human milk. We present two cases of lactating patients who donated milk samples to study the transfer of MMF into human milk following a week of 2 × 240 mg daily oral dose. Samples were analyzed using liquid chromatography mass spectrometry. The calculated relative infant dose was 0.019% and 0.007%. This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant.

Relapsing Remitting Multiple Sclerosis and its Relationship with the Immune System and Oxidative Stress

2018 ◽  
Vol 14 (1) ◽  
pp. 15-23
Author(s):  
Ada Paloma Soto-Brambila ◽  
Genaro Gabriel Ortiz ◽  
Paloma Rivero-Moragrega ◽  
Ana Laura Briones-Torres ◽  
Luis Javier Gonzalez-Ortiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Immune System ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
And Oxidative Stress

scholarly journals Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study

2019 ◽  
Vol 26 (13) ◽  
pp. 1729-1739 ◽  
Author(s):  
Robert T Naismith ◽  
Jerry S Wolinsky ◽  
Annette Wundes ◽  
Christopher LaGanke ◽  
Douglas L Arnold ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Tolerability Profile ◽  
Open Label ◽  
Phase 3 ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Monomethyl Fumarate ◽  
Favorable Safety ◽  
Relapsing Remitting Multiple Sclerosis

Background: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF’s distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. Objective: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. Methods: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. Results: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13–0.20). Conclusion: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS.

Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis

2018 ◽  
Vol 49 (6) ◽  
pp. 391-398 ◽  
Author(s):  
Angélica L. Sánchez-López ◽  
Genaro Gabriel Ortiz ◽  
Fermín P. Pacheco-Moises ◽  
Mario A. Mireles-Ramírez ◽  
Oscar K. Bitzer-Quintero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Inflammatory Cytokines ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

scholarly journals Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

2020 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Folami L. Powell ◽  
Pamela M. Martin
Keyword(s):  
Oxidative Stress ◽  
Fumaric Acid ◽  
Potential Benefit ◽  
Dimethyl Fumarate ◽  
The United States ◽  
Clinical Implementation ◽  
Us Fda ◽  
Fumaria Officinalis ◽  
And Oxidative Stress ◽  
Acid Esters

The medicinal benefit of salts of fumaric acid and its esters (FAE), known as fumarates (mono and dimethyl fumarate), was realized many years ago. Early on, FAE were derived from plants and mushrooms (e.g., Fumaria officinalis, Boletus fomentarius var. pseudo-igniarius). The FAE containing formulation Fumaderm® was licensed in Germany for the treatment of psoriasis in 1994. Recently, a clinical formulation of dimethyl fumarate known as BG12 (Tecfidera) was approved for use in the United States, New Zealand, Australia, European Union, Switzerland, and Canada for the treatment of multiple sclerosis. Others and we have assessed the potential benefit of FAE in a number of disease conditions that are diverse with respect to etiology but unified with regard to the involvement of inflammation and oxidative stress. Hence, a FAE-based drug with robust anti-oxidative and anti-inflammatory effects that is already US-FDA approved is a perfect contender for repurposing and rapid clinical implementation for their management. There is a burgeoning literature on the use of FAE in the prevention and treatment of diseases, other than psoriasis and MS, in which oxidative stress and/or inflammation are prominent. This chapter highlights critical information gleaned from these studies, exposes lacunae of potential importance, and provides related perspectives.

scholarly journals Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Valentina Pegoretti ◽  
Kathryn A. Swanson ◽  
John R. Bethea ◽  
Lesley Probert ◽  
Ulrich L. M. Eisel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Innate Immune ◽  
Autoimmune Response ◽  
Cns Inflammation ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Therapy Development ◽  
And Oxidative Stress ◽  
Ms Therapy ◽  
Complex Influence

CNS inflammation is a major driver of MS pathology. Differential immune responses, including the adaptive and the innate immune system, are observed at various stages of MS and drive disease development and progression. Next to these immune-mediated mechanisms, other mediators contribute to MS pathology. These include immune-independent cell death of oligodendrocytes and neurons as well as oxidative stress-induced tissue damage. In particular, the complex influence of oxidative stress on inflammation and vice versa makes therapeutic interference complex. All approved MS therapeutics work by modulating the autoimmune response. However, despite substantial developments in the treatment of the relapsing-remitting form of MS, approved therapies for the progressive forms of MS as well as for MS-associated concomitants are limited and much needed. Here, we summarize the contribution of inflammation and oxidative stress to MS pathology and discuss consequences for MS therapy development.

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