Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited
skin disease for which there is only supportive care. RDEB is due to mutations in COL7A1 gene
that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs)
mediating epidermal-dermal adherence. Approximately 20% of COL7A1 mutations are nonsense
mutations leading to premature stop codons and a truncated C7 with diminished function. The
investigators demonstrated that aminoglycosides such as gentamicin readily induce premature
termination codon (PTC) "read through" and produce biologically functional C7 in 22 reported
COL7A1 nonsense mutations. Importantly, aminoglycoside-induced C7 reversed the abnormal RDEB
cell phenotype and incorporated into the dermal-epidermal junction. Herein, the investigators
propose the first clinical trial of gentamicin (topical and intradermal) in RDEB patients
with nonsense mutations that the investigators have fully characterized. The milestones
include increased C7 and AFs at the patients' dermal-epidermal junction and absence of
significant gentamicin side effects.