Diacerein inhibits the pro-atherogenic &amp; pro-inflammatory effects of IL-1 on human keratinocytes &amp; endothelial cells

Mohan, Girish C.; Zhang, Huayi; Bao, Lei; Many, Benjamin T.; Chan, Lawrence S.

doi:10.1371/journal.pone.0173981

Cited by 18 publications

(12 citation statements)

References 70 publications

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“…Diacerein specifically targets IL-1b, a key player in the pathophysiology of EBS-gen/sev, as identified in previous studies. 5,22 In this study we confirmed superiority of a 1% diacerein cream over placebo in reducing the numbers of blister in patients with EBSgen/sev. A significant response was observed within the 4 weeks of treatment, with good persistence throughout the 3-month follow-up.…”

Section: Discussionsupporting

confidence: 70%

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial

Wally

Hovnanian

et al. 2018

Journal of the American Academy of Dermatology

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Section: Discussionsupporting

confidence: 70%

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial

Wally

Hovnanian

et al. 2018

Journal of the American Academy of Dermatology

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“…In a positive feedback loop, IL-1ß is activated and released from effected keratinocytes and, besides paracrine signaling, enhances the expression of KRT14, resulting in a perpetuum mobile-like state [66]. Diacerein, a small molecule derived from the rhubarb root, can interfere with the IL-1ß mediated inflammatory pathway at several levels [67][68][69][70][71][72][73]. In a phase II/III RCT that was based on a previous pilot study [74], diacerein was shown to significantly reduce blister numbers in sev-EBS patients in a 4-week treatment episode.…”

Section: Summary Of Publications On Recent (R)ct-trials and Current Cmentioning

confidence: 99%

Small molecule drug development for rare genodermatoses – evaluation of the current status in epidermolysis bullosa

Wally

Reisenberger

Kitzmüller

et al. 2020

Orphanet J Rare Dis

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Background Hereditary epidermolysis bullosa (EB) comprises a heterogeneous group of rare genodermatoses, which are caused by mutations in genes involved in the maintenance of the structural and functional integrity of dermo-epidermal adhesion in various stratified epithelia. In severe variants, generalized skin disease, extracutaneous manifestations and multi-organ involvement cause considerable morbidity and mortality. Causal and early treatment by re-expression of a respective mutated gene is the major long-term goal in therapy development. However, characterization and targeted modulation of pathogenic molecular cascades in EB also holds great promise as a symptom-relieving approach to ameliorate phenotype, complications and quality of life. Small molecules are chemical structures of less than 900 Da that can diffuse across cell membranes and interfere with target biomolecules, thus influencing their function at different levels. They constitute the vast majority of active components of all approved drugs. Methods We performed PubMed and Google Scholar search for publications and screened FDA- and EMA-hosted clinical trial registries to identify studies using small molecule-based drugs for epidermolysis bullosa. Upon detailed analysis this resulted in the identification of a total of 84 studies. Results We identified 52 publications and 32 registered trials that investigate small molecules for their safety and efficacy as treatment for different aspects of epidermolysis bullosa. Further, a total of 38 different small molecules clinically used in EB were found. Most frequent outcome measures concerned wound healing, reduction in blister numbers, as well as reduction of itch and pain, predominantly for EBS and RDEB. Conclusion We provide a comprehensive summary of the current status of clinical small molecule development for EB and discuss prospects and limitations in orphan drug development for rare conditions like EB.

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“…Topical therapies: Several different topical therapies have been tested in clinical trials for EB, all of them based on evidence from in vitro studies. Diacerein, an anti-inflammatory compound isolated from rhubarb root[42] has been shown to increase skin stability in EBS. [43] In classical EBS, keratin 5 and 14 mutations cause aggregation of the intermediate filament cytoskeleton and cell fragility.…”

Section: Newer Therapy Approachesmentioning

confidence: 99%

Newer treatment modalities in epidermolysis bullosa

Bruckner‐Tuderman

2019

Indian Dermatol Online J

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The term epidermolysis bullosa (EB) refers to a group of hereditary skin blistering diseases. The group is clinically and genetically heterogeneous, but all EB forms are associated with mechanically induced skin blistering and fragility. The causative gene mutations of most EB types are known. The current international consensus classification contains four main types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS). The classification is based on the morphological level of blister formation. In EBS, the split is intra-epidermal, in JEB along the basement membrane and in DEB below the basement membrane. In Kindler syndrome, the dermal-epidermal junction is disorganized, and blisters can occur on all three levels. Each major EB type has further subtypes which may differ in terms of their genetic, biological or clinical characteristics. Traditionally, EB treatments have been symptomatic, but increasing understanding of disease etio-pathogenesis is facilitating development of novel evidence-based therapy approaches. First gene- and cell-based therapies are being tested at preclinical level and in clinical trials. New knowledge on secondary disease mechanisms has led to development and clinical testing of urgently needed symptom-relief therapies using small molecules and biologicals.

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Diacerein inhibits the pro-atherogenic & pro-inflammatory effects of IL-1 on human keratinocytes & endothelial cells

Cited by 18 publications

References 70 publications

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial

Small molecule drug development for rare genodermatoses – evaluation of the current status in epidermolysis bullosa

Newer treatment modalities in epidermolysis bullosa

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