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Диметилфумарат используется для улучшения аневризмы аорты и диссекции у мышей.

Аневризма аорты и дискреция представляют угрозу смертельного исхода, однако эффективные методы лечения от наркотиков отсутствуют. Предыдущая работа была направлена на уменьшение факторов риска или на борьбу с ключевыми патологическими явлениями, однако ни одна из усилий по переводу не увенчалась успехом. Здесь мы пытаемся переделать диметилфумарат (DMF), одобренный УЛХ иммунодуляторный препарат для многократного склероза, для лечения аортальной аневризмы и диссекции. В трех доклинических моделях мыши брюшной аневризмы (полярная поджелудочная эластозная перфузия или инкубация CaCl2) и грудной а

Совпадение в аннотации оригинала
Aortic aneurysm and dissection pose fatal threats but no effective drug therapies are available. Previous work has been directed to reduce risk factors or target key pathological events, but none of the translational efforts succeeds. Here, we attempt to repurpose dimethyl fumarate (DMF), an FDA-approved immunomodulatory drug for multiple sclerosis, for the …

Incidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate.

BACKGROUND: Dimethyl fumarate (DMF) is a disease modifying therapy (DMT) used in the management of Multiple Sclerosis (MS). Lymphopenia occurs in approximately 30% of people receiving this medication. The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication in the context of persistent lymphopenia, because of an increased risk of progressive multifocal leukoencephalopathy (PML). It is therefore important for clinicians and patients to be aware of the frequency of persistent, moderate-severe lymphopenia in order to make inform…

An evaluation of dimethyl fumarate for the treatment of relapsing remitting multiple sclerosis.

INTRODUCTION: In recent years there has been a dramatic rise in available disease-modifying therapies for the treatment of relapsing multiple sclerosis (MS). Dimethyl fumarate (DMF) is an oral drug approved by the FDA for relapsing MS with unique immunomodulatory and cytoprotective effects. AREAS COVERED: Herein, the authors provide the reader with a review of the literature obtained via a PubMed database search and provide their expert opinion on the use of DMF in clinical practice. The article details DMF's mechanism of action, long-term data on efficacy, tolerability and safety. EXPERT OP…

Dimethyl fumarate induced lymphopenia in multiple sclerosis: A review of the literature.

Dimethyl fumarate (DMF) is a first line medication for multiple sclerosis. It has a favourable safety profile, however, there is concern regarding the occurrence of moderate-severe and sustained lymphopenia and the associated risk of progressive multifocal leukoencephalopathy. We carried out an extensive literature review to understand the molecular mechanisms underlying this adverse reaction. Dynamic changes in certain components of the immune system are likely to be important for the therapeutic effects of DMF, including depletion of memory T cells and decrease in activated T cells together …

Nanoformulations for dimethyl fumarate: Physicochemical characterization and in vitro/in vivo behavior.

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 w…

Возвращение диметила фумарата для лечения рака: текущие данные и будущие направления.

Диметилфумарат (DMF) является утвержденным лекарством УЛХ для лечения множественных склерозов, главным образом в целях выявления и регулирования траектории NF-IB. В последнее время его антираковые эффекты привлекли значительное внимание, поскольку он не только эффективно убивает панель различных раковых клеток in vitro и in vivo, но и синергирует с другими традиционными или целенаправленными химиотерапиями в некоторых устойчивых или рефракторных раковых клетках. Исследования, проведенные в рамках этого механизма, показали, что помимо сдерживания NF-ΔB и стимулирования Nrf2, DMF функционировал

Совпадение в аннотации оригинала
Dimethyl fumarate (DMF) is an approved medication by the FDA for the treatment of multiple sclerosis, primarily targeting and regulating the NF-κB pathway. Recently, its anticancer effects have drawn considerable attention as it not only effectively kills a panel of different cancer cells in vitro and in vivo, but also synergizes with other conventional or t…

Clinical effectiveness of dimethyl fumarate in multiple sclerosis patients from Argentina.

BACKGROUND: We assessed the effectiveness, safety and patient-reported outcomes (PROs) of dimethyl fumarate (DMF) in real-world clinical practice in patients with multiple sclerosis (PwMS) from Argentina. METHODS: We conducted a multicenter ambispective cohort study in Argentina between September 2020 and March 2023. Changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, magnetic resonance imaging (MRI), no evidence of disease activity (NEDA), PROs (depression, anxiety, fatigue, burden of treatment and quality of life), and safety data were collected at clini…

Dimethyl fumarate modulates the dystrophic disease program following short-term treatment.

New medicines are urgently required to treat the fatal neuromuscular disease Duchenne muscular dystrophy (DMD). Dimethyl fumarate (DMF) is a potent immunomodulatory small molecule nuclear erythroid 2-related factor 2 activator with current clinical utility in the treatment of multiple sclerosis and psoriasis that could be effective for DMD and rapidly translatable. Here, we tested 2 weeks of daily 100 mg/kg DMF versus 5 mg/kg standard-care prednisone (PRED) treatment in juvenile mdx mice with early symptomatic DMD. Both drugs modulated seed genes driving the DMD disease program and improved fo…

Case Report: Anti-MOG Antibody Seroconversion Accompanied by Dimethyl Fumarate Treatment.

Here we report three cases of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) mimicking multiple sclerosis in which seropositivity for anti-MOG antibodies occurred during disease-modifying drug dimethyl fumarate (DMF) treatment. These patients developed relapses with anti-MOG antibody seroconversion after switching from fingolimod or steroid pulse therapy to DMF, which was associated with peripheral lymphocyte recovery. MOGAD is considered a humoral immune disease, and DMF reportedly enhances Th2-skewed humoral immune activity. Therefore, we suggest that DMF,…

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis.

INTRODUCTION: Dimethyl-fumarate is a recently approved drug for relapsing-remitting Multiple Sclerosis in Italy. CLINICAL CASE: A 55-year-old woman started therapy with dimethyl-fumarate on June 2014; it was well-tolerated aside from moderate flushing. Starting September 2014 she noticed a progressive hair loss, that neither the dermatological examination nor clinical and medical history nor blood investigations could explain. The hair loss slowed down after two months and was followed by a hair growth back. DISCUSSION: Transient hair loss is not a reported side effect of dimethyl-fumarate t

Lymphocyte count polygenicity underlies dimethyl fumarate-associated lymphopenia in multiple sclerosis.

PURPOSE: One in 20 people using dimethyl fumarate (DMF), a commonly used disease-modifying therapy for multiple sclerosis (MS), develops severe lymphopenia. We aimed to identify genetic variation associated with DMF-related lymphopenia. METHODS: Using a case-control design, we included cases that had either grade 2 (absolute lymphocyte count <0.8 × 109/L) or 3 (<0.5 × 109/L) lymphopenia during DMF. Controls had normal lymphocyte counts and ⩾1 year of DMF exposure. We generated a polygenic score for lymphocyte counts and evaluated its ability to predict DMF-associated lymphopenia in two cohort…

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 …

Sleep-related breathing disorder (central sleep apnoea) improved coincidentally by medical therapy with fumarates (dimethyl fumarate).

Central sleep apnoea (CSA) is a sleep disorder characterized by the repeated cessation or reduction of both airflow and ventilatory effort when sleeping. Individuals with central breathing disorders have difficulty in receiving appropriate medical treatment. In this article, we describe a case study of a 31-year-old woman known to have multiple sclerosis and concomitant severe CSA. She received the medication dimethyl fumarate for the treatment of multiple sclerosis, and her CSA significantly improved to mild CSA after the treatment.

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…

Dimethyl fumarate ameliorates quinolinic acid-induced ageing and neurodegeneration in Caenorhabditis elegans.

The ageing population and the increasing prevalence of age-related diseases underscore the urgent need for targeted therapeutic strategies. … ng this QA-induced injury model, we investigated the therapeutic potential of the clinical compound dimethyl fumarate (DMF), a derivative of a tricarboxylic acid cycle intermediate, and revealed that DMF's protective effects are partially dependent on the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In summary, our results demonstra …

Диметил фумарат защищает от экспериментального аутоиммунного энцефаломиэлита путем модуляции колонических иммунных клеток.

Диметилфумарат (DMF) представляет собой пероральную терапию, утвержденную для лечения повторно излучающего многократного склероза, и известно, что она снижает остроту заболеваний при экспериментальном аутоиммунном энцфаломиелите (EAE). Поскольку считается, что самореактивные лимфоциты TH17 активируются в кишечнике до перехода в центральную нервную систему (КНС), мы изучили, как DMF модифицирует кишечную иммунную реакцию во время EAE. Женские мыши C57BL/6J были иммунизированы MOG35-55 для стимулирования EAE и обработки с помощью DMF (7.5 мг/кг, пероральный желудок, каждый 12 h) либо транспортно

Совпадение в аннотации оригинала
Dimethyl fumarate (DMF) is an oral therapy approved for the treatment of relapsing-remitting multiple sclerosis, and it is known to reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Because self-reactive Th17 lymphocytes are thought to become activated in the gut before migrating to the central nervous system (CNS), we investigated …

Диметилфумарат уменьшает травму от печени ишемии и реперуляции путем подавления сигнала CGAS-STING.

Повреждение печени во время периоперационной фазы операции на печени часто происходит в результате печени. Неправильная активация сигнала СТИНГ может вызвать чрезмерную воспламенение реакции на усугубление печени. Диметилфумарат (DMF) — разрешенный УЛХ иммунодулятор, используемый для лечения множественного склероза и псориаза в силу его заметных свойств против воспаления. Однако механизм и целевые показатели ДМФ в области иммуномодуляции остаются неясными. Здесь мы обнаружили, что DMF подавляет активацию CGAS-STING, индуцируемую HSV-1, ДНК яичек и митохондриальная ДНК в различных клетках. DMF

Совпадение в аннотации оригинала
Hepatic ischemia-reperfusion (I/R) injury frequently occurs during the perioperative phase of liver surgery. Inappropriate activation of STING signaling can trigger excessive inflammation response to aggravate hepatic I/R injury. Dimethyl fumarate (DMF) is an FDA-approved immunomodulatory drug used to treat multiple sclerosis and psoriasis due to its notable…

Comparative analysis of dimethyl fumarate and teriflunomide in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: In relapsing-remitting multiple sclerosis (RRMS), analyses from observational studies comparing dimethyl fumarate (DMF) and teriflunomide showed conflicting results. We aimed to compare the effectiveness of DMF and teriflunomide in a real-world setting, where both drugs are licensed as first-line therapies for RRMS. METHODS: We included all patients who initiated DMF or teriflunomide between 2013 and 2022, listed in the Swiss National Treatment Registry. Coarsened exact matching was applied using age, gender, disease duration, baseline Expanded Disability Status Scale …

Bariatric surgery and dimethyl fumarate-induced lymphopenia in patients with multiple sclerosis.

INTRODUCTION: Lymphopenia is a known side effect of dimethyl fumarate (DMF), a disease-modifying therapy (DMT) for patients with multiple sclerosis (pwMS). A body mass index ≥ 30 kg/m2 has been identified as a protective factor; however, no data are available on lymphopenia in pwMS undergoing to weight loss due to bariatric surgery. METHODS: We described two pwMS with history of bariatric surgery who started DMF as DMT. RESULTS: The two pwMS experienced persistent lymphopenia during DMF-treatment, which was resolved after its discontinuation. CONCLUSIONS: Several mechanisms might modify DMF…

Gut Microbiota Changes during Dimethyl Fumarate Treatment in Patients with Multiple Sclerosis.

The gut microbiota is involved in the development of the immune system and can modulate the risk for immune-mediated disorders such as multiple sclerosis (MS). Dysbiosis has been demonstrated in MS patients and its restoration by disease-modifying treatments (DMTs) is hypothesized. We aimed to study the changes in gut microbiota composition during the first 6 months of treatment with dimethyl fumarate (DMF), an oral DMT, and to identify the microorganisms associated with DMF side effects. We collected and analyzed the gut microbiota of 19 MS patients at baseline and after 1, 3, and 6 months of…