Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa Patients With Nonsense Mutations

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited
skin disease caused by mutations in the COL7A1 gene that encodes for type VII collagen (C7),
the major component of anchoring fibrils (AFs), structures that mediate epidermal-dermal
adherence. Thirty percent of RDEB patients have nonsense mutations. The investigators
recently demonstrated in 5 such patients that intradermal and topical gentamicin induced
"read-through" of their nonsense mutations and created robust and sustained new C7 and AFs
at the dermal-epidermal junction (DEJ) of their skin and also stimulated wound closure and
reduced new blister formation. No untoward side effects occurred. Herein, the investigators
propose evaluating the safety and efficacy of intravenous gentamicin in these patients. In
theory, this intravenous administration has the possibility of treating simultaneously all
of the patients' skin wounds. The investigators also propose optimizing the concentration
and manner of delivery of topical gentamicin. The unambiguous milestones will be increased
C7 and AFs in the patients' DEJ, improved EB Disease Activity Scores, and absence of
significant gentamicin side effects.