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.