Epidermolysis bullosa pruriginosa treated with dupilumab

Zhou, Amanda; Little, Alicia J.; Antaya, Richard J.

doi:10.1111/pde.14493

Cited by 35 publications

(34 citation statements)

References 5 publications

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“…[4][5][6][7] Two previous reports have documented successful treatment of EBP with dupilumab, a monoclonal antibody that provides dual blockade of IL-4 and IL-13 by targeting the a subunit of the IL-4 receptor (IL-4Ra). 8,9 The mechanism of dupilumab's efficacy in EBP is unknown, but it has been proposed that it blocks the IL-4Ra-induced sensitization of sensory neurons to pruritogens. 10…”

Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa pruriginosa responding to dupilumab

2021

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Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa pruriginosa responding to dupilumab

2021

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“…Treatment with 3 months of dupilumab injections every other week (600 mg loading dose plus 300 mg maintenance dose) led to marked pruritus reduction with clinical improvement in skin lesions [131]. Other reports have also shown benefits from dupilumab in EB pruriginosa [132].…”

Section: Deb-biologicsmentioning

confidence: 97%

Investigational Treatments for Epidermolysis Bullosa

et al. 2021

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Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management.

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“…AC-203 is another drug with similar properties, which is currently under investigation (Table 1). Targeting Th-17 cells, as well as TGF-β or Th-2 cytokines represent other therapeutic options (Nyström et al, 2015;Castela et al, 2019;Shehadeh et al, 2020;Zhou et al, 2021).…”

Section: Targeted Therapies For Components Of Inflammatory Pathwaysmentioning

confidence: 99%

Challenges in Treating Genodermatoses: New Therapies at the Horizon

Morren

Legius

Giuliano³

et al. 2022

Front. Pharmacol.

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Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a “read through” strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus.

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Epidermolysis bullosa pruriginosa treated with dupilumab

Cited by 35 publications

References 5 publications

Epidermolysis bullosa pruriginosa responding to dupilumab

Epidermolysis bullosa pruriginosa responding to dupilumab

Investigational Treatments for Epidermolysis Bullosa

Challenges in Treating Genodermatoses: New Therapies at the Horizon

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