View clinical trials related to Junctional Epidermolysis Bullosa.
Filter by:Herlitz junctional epidermolysis bullosa (H-JEB), an incurable and fatal inherited skin disease, is caused by loss-of-function mutations in LAMA3, LAMB3 and LAMC2. These mutations result in diminished laminin 332 and epidermal-dermal adherence. 85% of JEB patients have nonsense mutations in LAMA3, LAMB3, or LAMC2, suggesting that H-JEB is a prime therapeutic target for nonsense suppression therapy. The investigators recently demonstrated in three patients that topical gentamicin created new and stable laminin 332 at the dermal-epidermal junction (DEJ), and also improved wound closure and skin quality. Furthermore, these preliminary studies showed that intravenous gentamicin also induced laminin 332 and transiently improved patients' clinical outcomes. No untoward side effects occurred. The investigators propose to optimize the intravenous gentamicin regimen including dosage and infusion schedules to enhance the therapeutic outcome. The milestones will be an increase of laminin 332 in the patients' DEJ, improvement in EB Disease Activity Scores, and no gentamicin-associated side effects.
Herlitz junctional epidermolysis bullosa (H-JEB), an incurable, fatal, inherited skin disease, is caused by loss-of-function mutations in the LAMA3, LAMB3 or LAMC2 genes, resulting in loss of laminin 332 and poor epidermal-dermal adherence. Eighty percent of H-JEB patients have LAMB3 mutations and about 95% of these are nonsense mutations. The investigators recently demonstrated that gentamicin readily induced nonsense mutation readthrough and produced full-length laminin beta3 in several nonsense mutations tested. Importantly, the gentamicin-induced laminin beta3 restored laminin 332 assembly, secretion, and deposition into the dermal-epidermal junction (DEJ). Newly induced laminin 332 reversed abnormal H-JEB cellular phenotypes. Herein, the investigators propose the first clinical trial of gentamicin (by topical and intravenous administration) in JEB patients with nonsense mutations. The milestones will include restored laminin 332 and hemidesmosomes at the DEJ, improved wound closure, and the absence of significant gentamicin side effects.