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Dimethyl fumarate mitigates optic neuritis.

PURPOSE: Dimethyl fumarate (DMF) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing-remitting multiple sclerosis (RRMS), a demyelinating autoimmune disease characterized by acute episodes of motor, sensory, and cognitive symptoms. Optic neuritis is an episodic sequela experienced by some patients with RRMS that typically presents as acute, monocular vision loss. Episodes of optic neuritis damage and kill retinal ganglion cells (RGCs), and can culminate in permanent vision loss. The purpose of these studies was to evaluate the capacity of DMF to miti

Effects of dimethyl fumarate on lymphocyte subsets.

OBJECTIVE: To evaluate changes in absolute lymphocyte counts, lymphocyte subsets, and infections in patients treated with dimethyl fumarate (DMF) in comparison to the baseline pre-DMF levels. METHODS: A retrospective chart review was conducted of 23 MS patients treated with DMF. Absolute lymphocyte counts and lymphocyte subsets were obtained at baseline and after at least 3 months of DMF treatment. Data on infections requiring medical attention were also collected. RESULTS: A total of 23 patients were included in this analysis, 11 male (48%), 12 female (52%), with a mean age of 44.5±14.1 yea

Oral fumaric acid esters for psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries. OBJECTIVES: To assess the effects and safety of oral fumaric acid esters for psoriasis. SEARCH METHODS: We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in

Dimethyl fumarate : a Janus-faced substance?

INTRODUCTION: Dimethyl fumarate (DMF) has been used as fungicide, but oral DMF activates anti-inflammatory and anti-oxidative pathways that are beneficial in the treatment of psoriasis. BG-12, a specific formulation of DMF, has been approved very recently for the treatment of relapsing-remitting multiple sclerosis (RRMS), which is characterized by both autoimmune lymphocytes leading to inflammation and mitochondrial alterations associated with oxidative stress. AREAS COVERED: This review describes the pharmacokinetics and the mode of action of DMF, with a focus on molecular and cellular pathw

[Contact dermatitis due to dimethyl fumarate].

Dimethyl fumarate is a fumaric acid ester. It been used for some years to treat psoriasis and also as a preservative in desiccant sachets in the transport of furniture and footwear. Its irritant properties and sensitizing potential in contact with the skin were recently highlighted when it was implicated as the causative agent in 2 epidemics of severe acute eczema: sofa dermatitis in northern Europe and shoe dermatitis in Spain. The present article aims to guide dermatologists in the diagnosis and management of patients allergic to dimethyl fumarate. We review the clinical manifestations, resu

Use of fumaric acid esters in psoriasis.

Fumaric acid esters (FAE) are chemical compounds derived from the unsaturated dicarbonic acid fumaric acid. The usage of FAEs in treatment of psoriasis was introduced in the late 1950's. In the 1980s more standardized oral preparations of FAEs were developed containing dimethylfumarate (DMF) and salts of monoethylfumarate (MEF) as main compounds. In 1994, Fumaderm an enteric-coated tablet containing DMF and calcium, magnesium and zinc salts of MEF was approved for the treatment of psoriasis in Germany and since then has become the most commonly used systemic therapy in this country. Fumaric ac

A Randomised, Double-Blind Study Comparing the Gastrointestinal Tolerability of Tegomil Fumarate Versus Dimethyl Fumarate in Healthy Volunteers.

INTRODUCTION: Widely used to treat multiple sclerosis, dimethyl fumarate (DMF) is a prodrug metabolized in vivo to monomethyl fumarate (MMF) and methanol; the latter is a gastrointestinal (GI) irritant. GI adverse events (AEs) commonly cause DMF discontinuation. Tegomil fumarate (TMF) comprises two MMF moieties joined by tetraethylene glycol, a low molecular polyethylene glycol (PEG). TMF is cleaved in vivo to MMF and the pharmacologically inactive PEG. METHODS: This randomised, double-blind study compared the GI tolerability of TMF 348 mg and DMF 240 mg, administered twice daily, in healthy

Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data.

Fumarates (fumaric acid esters, FAEs) are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. In 1994, a proprietary combination of FAEs was licensed for psoriasis by the German Drug Administration for use within Germany. Since then, fumarates have been established as one of the most commonly used treatments for moderate-to-severe psoriasis in Germany and other countries. The licensed FAE formulation contains dimethyl fumarate (DMF), as well as calcium, zinc, and magnesium salts of monoethyl fumarate (MEF). While the clinical efficacy of this FAE mix…

An Exploratory Pharmacogenetic Pilot Study of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate.

BACKGROUND AND OBJECTIVES: The nucleoside reverse transcriptase inhibitors tenofovir alafenamide fumarate and tenofovir disoproxil fumarate are frequently employed in treating human immunodeficiency virus. Further, each form of tenofovir requires laboratory monitoring to determine efficacy and tolerability among patients. This study sought to investigate the relationship, if any, of single nucleotide polymorphisms (SNPs) and selected clinical parameters. METHODS: The study population, predominantly Caucasian males with a median age of 53.0 years [interquartile range 46.0-59.0], was assayed fo

A Sensitization-Free Dimethyl Fumarate Prodrug, Isosorbide Di-(Methyl Fumarate), Provides a Topical Treatment Candidate for Psoriasis.

Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes sh

Switch of psoriasis therapy from a fumaric acid ester mixture to dimethyl fumarate monotherapy: Results of a prospective study.

BACKGROUND: Fumaric acid esters (FAEs) are used for systemic therapy of moderate to severe psoriasis. Until recently, only a mixture of dimethyl fumarate (DMF) and three salts of ethyl hydrogen fumarate was available. However, a drug containing DMF as the sole ingredient was registered for the same indication in 2017. This prospective study aimed to investigate the switch from the currently used FAE mixture to DMF alone. PATIENTS AND METHODS: Forty patients were consecutively recruited, for whom the FAE mixture was switched to DMF alone on the basis of the last DMF-equivalent dose without int

Сравнительная эффективность Diroximel Fumarate vs. Диметил Фумарат у лиц с множественным склерозом: анализ претензий США в отношении релапсовых результатов.

ВВЕДЕНИЕ: Дирошимель фумарат (DRF) и диметилфумарат (DMF) представляют собой лекарственные средства для изменения заболеваний в связи с повторным склерозом (RMS). Несмотря на то, что ДРР продемонстрировал более высокую терпимость к желудочно-кишечному кишечнику по сравнению с ДМФ, в настоящее время проводятся ограниченные исследования для оценки того, приводит ли эта разница в терпимости к клинической эффективности. В этом исследовании была дана оценка реальной эффективности ДРР и ДМФ в сравнении с результатами рецидивов у лиц, имеющих МЗС (PwMS) у большого населения США. МЕТОДЫ: В этом ретрос

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… Among these, fumarates, including dimethyl fumarate (DMF) and diroximel fumarate (DRF), have demonstrated robust efficacy in reducing relapse burden in pivotal clinical trials and long-term extension studies [ 4 – 7 ]. … DMF dimethyl fumarate, DRF diroximel fumarate, pwMS persons with multiple sclerosis In the 2-year follow-up population (Fig. 4 ), Kaplan–Meier curves for DRF and DMF groups achieved consistent numerical separation post-index. …

Efficacy and safety of ofatumumab in participants with relapsing multiple sclerosis and breakthrough disease on oral fingolimod or fumarates: results from the ARTIOS study.

BACKGROUND: Initiating high-efficacy disease-modifying therapies (DMTs) early in relapsing multiple sclerosis (RMS) can reduce inflammation and limit disability progression; however, moderate-efficacy oral DMTs remain common first-line treatments. Ofatumumab demonstrated superior efficacy and tolerable safety in the phase 3 ASCLEPIOS trials, although few participants (≤ 5%) transitioned from oral DMTs. ARTIOS evaluated the efficacy and safety of ofatumumab in adults with RMS switching from fingolimod or fumarates following breakthrough disease. METHODS: ARTIOS was a phase 3b, open-label, sing…

Accuracy of Magnetic Resonance Spectroscopy-Detected Fumarate Peak for Diagnosing Fumarate Hydratase Deficiency in Uterine Leiomyomas: A Prospective Study.

OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. MATERIALS AND METHODS: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20-40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation pa

Fumarate Mediates a Chronic Proliferative Signal in Fumarate Hydratase-Inactivated Cancer Cells by Increasing Transcription and Translation of Ferritin Genes.

Germ line mutations of the gene encoding the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC-associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite fumarate. Although it is known that fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remain unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling. Speci

Mitochondrial fumarate inhibits Parkin-mediated mitophagy.

Here, we explore the potential involvement of fumarate, a metabolite generated from the TCA cycle, as a key regulator of PINK1-Parkin-mediated mitophagy. Fumarate engages in a process called succination, forming S-(2-succino) cysteine with protein cysteine residues. Our research demonstrates that this modification specifically targets the sulfhydryl group of cysteine 323 and 451 residues of human Parkin, leading to the inhibition of its mitochondrial localization and E3 ligase activity, thereby impeding PINK1-Parkin-mediated mitophagy. Notably, our investigation reveals that the succinatable c