849 Optimization of intravenous gentamicin to restore functional laminin 332 in junctional epidermolysis bullosa patients harboring nonsense mutations
نویسندگان
چکیده
Junctional epidermolysis bullosa (JEB) is an incurable and fatal inherited blistering skin disease most commonly caused by nonsense mutations in LAMA3, LAMB3, or LAMC2 genes. These impair the ability to produce functional laminin 332, needed for epidermal-dermal adherence. Previously, we demonstrated that intravenous (IV) gentamicin daily at 7.5 mg/kg two weeks promoted readthrough of produced 332. Here, determined if treating patients with higher doses more prolonged treatment would induce provide long-term clinical improvement. We administered IV JEB either LAMB3 LAMA3. At day 0, multiple Test Sites from open wounds intact were selected measuring wound closure. Both received biweekly infusions 10 3 months. Skin biopsies examined expression evaluated using standardized photographs before one three months after treatment. also patients’ overall improvement EB activity scores. displayed newly created, properly localized 332 dermal-epidermal junction skin. In addition, closure improved Most interestingly, observed airway symptoms patients. Lastly, increasing dosage duration resulted greater did not detect any adverse effects auto-antibodies against new An optimized dose may be a readily available, safe potentially efficacious therapy reduces severity this population
منابع مشابه
Junctional epidermolysis bullosa.
Epidermolysis bullosa (EB) encompasses a heterogeneous group of genodermatoses, characterized by fragility and blistering of the skin, often associated with extracutaneous manifestations. The level of vesiculation within the skin defines 3 major subtypes of EB: EB simplex, junctional EB, and dystrophic EB. We present the case of a male neonate of 36 weeks of gestation, who was born with a few b...
متن کاملJunctional and Dystrophic Epidermolysis Bullosa
Epidermolysis bullosa (EB) is a congenital genodermatosis, which affects mainly skin and occasionally other organs [1]. Lifelong blistering and erosion of the skin and mucous membrane, caused by mechanical trauma, threaten EB patients [1]. The most common cause of death is metastasizing squamous cell carcinoma [2]. EB is subdivided into mainly three categories by the location of tissue separati...
متن کاملJunctional Epidermolysis Bullosa in Belgian Draft Horses
The mutation responsible for Junctional Epidermolysis Bullosa (JEB) in Belgian draft horses in North America and other draft breeds in Europe has been identified. The mutation, a cytosine insertion (1368 insC) in the LAMC2 gene, results in absent expression of the laminin γ2 polypeptide chain of laminin 5. JEB is inherited as an autosomal recessive trait. A polymerase chain reaction (PCR) test ...
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.863