Treatment With Ataluren for Wound Healing and Health Complications in a Patient With Junctional Epidermolysis Bullosa

Orlowski, Gregory M.; Amano, Sadao; Flanagan, Kelly; Rieger, Kerri E.; Marinkovich, M. Peter; Wiss, K

doi:10.1001/jamadermatol.2023.2077

Cited by 4 publications

(2 citation statements)

References 8 publications

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“…Orlowski et al reported a case of an 11-year-old boy suffering from junctional EB. 65 Treatment with orally administered PTC-124 three times daily at concentrations of 10-10-20 mg/kg (morning-noon-evening) were well tolerated. The drug was shown to significantly reduce the number and duration of hospitalization events during the treatment period and, thus, ameliorated the patient's skin condition as supported by the detection of low levels of laminin-332 subunits by immunofluorescence microscopy.…”

Section: Non -Aminog Lycos Ide Comp Oundsmentioning

confidence: 98%

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Stop codon readthrough as a treatment option for epidermolysis bullosa—Where we are and where we are going

Zandanell,

Wießner,

Bauer

et al. 2024

Experimental Dermatology

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In the context of rare genetic diseases caused by nonsense mutations, the concept of induced stop codon readthrough (SCR) represents an attractive avenue in the ongoing search for improved treatment options. Epidermolysis bullosa (EB)—exemplary for this group of diseases—describes a diverse group of rare, blistering genodermatoses. Characterized by extreme skin fragility upon minor mechanical trauma, the most severe forms often result from nonsense mutations that lead to premature translation termination and loss of function of essential proteins at the dermo‐epidermal junction. Since no curative interventions are currently available, medical care is mainly limited to alleviating symptoms and preventing complications. Complementary to attempts of gene, cell and protein therapy in EB, SCR represents a promising medical alternative. While gentamicin has already been examined in several clinical trials involving EB, other potent SCR inducers, such as ataluren, may also show promise in treating the hitherto non‐curative disease. In addition to the extensively studied aminoglycosides and their derivatives, several other substance classes—non‐aminoglycoside antibiotics and non‐aminoglycoside compounds—are currently under investigation. The extensive data gathered in numerous in vitro experiments and the perspectives they reveal in the clinical setting will be discussed in this review.

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Section: Non -Aminog Lycos Ide Comp Oundsmentioning

confidence: 98%

“…Orlowski et al. reported a case of an 11‐year‐old boy suffering from junctional EB 65 . Treatment with orally administered PTC‐124 three times daily at concentrations of 10–10–20 mg/kg (morning–noon–evening) were well tolerated.…”

Section: Non‐aminoglycoside Compoundsmentioning

confidence: 99%

Stop codon readthrough as a treatment option for epidermolysis bullosa—Where we are and where we are going

Zandanell,

Wießner,

Bauer

et al. 2024

Experimental Dermatology

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Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

Prodinger,

Laimer

2024

hautnah

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ZusammenfassungEpidermolysis bullosa (EB) bezeichnet eine seltene, heterogene Gruppe von Genodermatosen, charakterisiert durch eine gesteigerte Fragilität von Haut und Schleimhaut. Mit zunehmender Aufklärung der molekularen Pathophysiologie haben sich in den letzten Jahren sämtliche lokale und systemische Therapieansätze in klinischen Studien etabliert. Ein bedeutender Meilenstein ist die Zulassung der FDA für die topische Gentherapie Beremagene Geperpavec (B-VEC) zur Behandlung chronischer Wunden bei dystropher EB mit Mutationen im COL7A1-Gen. Diese Therapie basiert auf modifizierten HSV-1-Vektoren, um funktionales COL7A1 in die Hautzellen zu übertagen. In einer Phase-3-Studie zeigten sich etwa drei Viertel der chronischen Wunden nach 3 Monaten komplett verschlossen, im Vergleich zu 20 % in der Placebogruppe. Klinische Studien mit RNA-basierten Therapien, wie medikamentös induzierte PTC-Readthrough und zellbasierten Therapien wie ABCB5+ mesenchymale Stammzellen zeigen Potenzial für weiteren Einsatz. Durch das 2022 speziell für EB zugelassene Filsuvez® Gel (Oleogel S‑10, Chiesi, Wien) und das topische Vitamin-D-Analogon Calcipotriol kann die Wundheilung verbessert werden, während TGF-β-Inhibitoren, z. B. Losartan, die EB-assoziierte Fibrose adressieren. Biologika wie Dupilumab, JAK- und mTOR-Inhibitoren erweitern das therapeutische Armamentarium. Immuntherapien gelten aktuell als First-line-Therapie für aggressive EB assoziierte Plattenepithelkarzinome und werden neben Multikinase-Inhibitoren (Rigosertib) in Studien untersucht. Zukünftig könnten auch MikroRNA sowohl in der Frühdiagnostik als auch topisch zur Reduktion der Tumoraggressivität eingesetzt werden. Insgesamt markieren diese Entwicklungen einen bedeutsamen Fortschritt in der therapeutischen Landschaft von EB und vermitteln Hoffnung für Betroffene und Angehörige.

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Treatment of Epidermolysis Bullosa and Future Directions: A Review

Danescu,

Negrutiu,

Has

2024

Dermatol Ther (Heidelb)

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Epidermolysis bullosa (EB) comprises rare genetic disorders characterized by skin and mucosal membrane blistering induced by mechanical trauma. Molecularly, pathogenic variants affect genes encoding proteins crucial for epidermal–dermal adhesion and stability. Management of severe EB is multidisciplinary, focusing on wound healing support, ensuring that patients thrive, and complication treatment. Despite extensive research over 30 years, novel therapeutic approaches face challenges. Gene therapy and protein therapy struggle with efficacy, while regenerative cell-based therapies show limited effects. Drug repurposing to target various pathogenic mechanisms has gained attention, as has in vivo gene therapy with drugs for dystrophic and junctional EB that were recently approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). However, their high cost limits global accessibility. This review examines therapeutic advancements made over the past 5 years, exploiting a systematic literature review and clinical trial data.

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Treatment With Ataluren for Wound Healing and Health Complications in a Patient With Junctional Epidermolysis Bullosa

Abstract: This case report describes an 11-year-old boy with widespread chronic wounds, frequent corneal erosions, dental caries, a tracheostomy, and failure to thrive.

Cited by 4 publications

References 8 publications

Stop codon readthrough as a treatment option for epidermolysis bullosa—Where we are and where we are going

Stop codon readthrough as a treatment option for epidermolysis bullosa—Where we are and where we are going

Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

Treatment of Epidermolysis Bullosa and Future Directions: A Review

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