Dimethyl fumarate – only an anti‐psoriatic medication?

Meißner, Markus; Valesky, Eva Maria; Kippenberger, Stefan; Kaufmann, Roland

doi:10.1111/j.1610-0387.2012.07996.x

Cited by 66 publications

(72 citation statements)

References 61 publications

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“…21 Consequently, marked clinically apparent immunosuppression usually does not result from DMF treatment, despite its pleiotropic cellular effects. [25][26][27] For diseases such as psoriasis and multiple sclerosis, DMF is approved and clinically used. [21][22][23] The drug has also shown favorable effects in off-label treatment of a wide variety of inflammatory and immunological diseases.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23] The drug has also shown favorable effects in off-label treatment of a wide variety of inflammatory and immunological diseases. 25 In addition, DMF is characterized by a profile of rather mild side effects, which makes it a fairly well-tolerated drug. This is especially attractive for the clinical prospects of DMF as a potential medication for CTCL because many other oncological treatment options are limited by acute or cumulative toxicity or adverse effects.…”

Section: Introductionmentioning

confidence: 99%

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Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Nicolay

Müller‐Decker

Schroeder

et al. 2016

Blood

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Key Points• DMF induces specific cell death in CTCL cells and inhibits CTCL tumor growth and metastasis in vivo via inhibition of NF-kB.• DMF therefore represents a promising, nontoxic novel therapeutic approach to treating CTCL.Despite intensive efforts in recent years, a curative therapy for cutaneous T-cell lymphoma (CTCL) has not yet been developed. Therefore, the establishment of new therapeutic approaches with higher efficacy rates and milder side effects is strongly desired. A characteristic feature of the malignant T-cell population in CTCL is resistance toward cell death resulting from constitutive NF-kB activation. Therefore, NF-kBdependent cell death resistance represents an interesting therapeutic target in CTCL because an NF-kB-directed therapy would leave bystander T cells widely unaffected. We investigated the effects of dimethyl fumarate (DMF) on CTCL cells in vitro and in vivo. DMF induced cell death in primary patient-derived CD4 1 cells and CTCL cell lines, but hardly in T cells from healthy donors. DMF-induced cell death was linked specifically to NF-kB inhibition. To study the impact of DMF in vivo, we developed 2 CTCL xenograft mouse models with different cutaneous localizations of the T-cell infiltrate. DMF treatment delayed the growth of CTCL tumors and prevented formation of distant metastases. In addition, DMF induced increased cell death in primary CTCL tumors and in liver metastases. In summary, DMF treatment represents a remarkable therapeutic option in CTCL because it restores CTCL apoptosis in vitro and in preclinical models in vivo and prevents spreading of the disease to distant sites. DMF treatment is of particular promise in CTCL because DMF is already in successful clinical use in the treatment of psoriasis and multiple sclerosis allowing fast translation into clinical studies in CTCL. (Blood. 2016;128(6):805-815)

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Nicolay

Müller‐Decker

Schroeder

et al. 2016

Blood

View full text Add to dashboard Cite

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“…7,8 Since 1959, fumaric acid esters (FAEs) have been used for the treatment of psoriasis. 9 In 1994, Fumaderm, a combination of DMF and monomethyl fumarate, was approved in Germany for the treatment of moderate to severe psoriasis. 9 FAEs shift the proinflammatory Th1 cellular response to a less inflammatory Th2 response.…”

Section: Safetymentioning

confidence: 99%

“…9 In 1994, Fumaderm, a combination of DMF and monomethyl fumarate, was approved in Germany for the treatment of moderate to severe psoriasis. 9 FAEs shift the proinflammatory Th1 cellular response to a less inflammatory Th2 response. 10 The exact mechanism of DMF in vivo in MS has not been fully elucidated, but several in vitro studies have suggested the following mechanisms.…”

Section: Safetymentioning

confidence: 99%

Multiple sclerosis

2013

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“…Fumaric acid esters (FAE) such as dimethyl fumarate (DMF) have potent anti-oxidative and anti-inflammatory effects [1,4]. Inflammation and oxidative stress play important roles in the pathogenesis of obesity, diabetes, and related metabolic and cardiovascular disorders [2,5].…”

Section: Discussionmentioning

confidence: 99%

Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats

et al. 2014

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Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE) treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP), will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFa) and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma). FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important antiinflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.Citation: Šilhavý J, Zídek V, Mlejnek P, Landa V, Šimáková M, et al.

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Dimethyl fumarate – only an anti‐psoriatic medication?

Cited by 66 publications

References 61 publications

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Multiple sclerosis

Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats

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