Optimizing IV Gentamicin in JEB

• Status: Unknown status
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Southern California
• Treatments: Gentamicins

Criteria

Inclusion Criteria:

• JEB patients with nonsense mutations in LAMB3 or LAMA3 in either one or two alleles

• Immunofluorescence (IF) analysis showing absence or decreased laminin 332 expression at their DEJ compared with normal skin.

Exclusion Criteria:

• Pre-existing known auditory impairment.

• Pre-existing known renal impairment.

• Pre-existing known allergies to aminoglycosides or sulfate compounds.

• Pregnancy.

• Recent exposure to systemic gentamicin within the past 6 weeks.

• Current use of any medications with known potential ototoxicity or nephrotoxicity.