Gentamicin for Junctional Epidermolysis Bullosa

Conditions

• Junctional Epidermolysis Bullosa

Eligibility Criteria

Sex

ALL

Age

N/A - N/A

Healthy Volunteers

Not accepted

Interventions

• Gentamicin Sulfate — DRUG
  Gentamicin (formulated as gentamicin sulfate) is a well-known, well-characterized antibiotic that has been used for four decades as a treatment against gram negative bacteria. It, like other aminoglycoside antibiotics, has the well documented added potential to facilitate readthrough of premature termination codons in eukaryotic cells and organisms.

Study Details

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.

Key Dates

Start date

Jun 1, 2018

Status verified

Apr 2020

Primary completion

Jul 30, 2020

Completion

Aug 31, 2020

Study Design

Enrollment

6 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Gentamicin Sulfate
  IV Arm: 7.5 mg/kg gentamicin once daily for 14 days. Topical Arm: 0.5% gentamicin ointment applied twice daily for 14 days to selected skin sites.

Primary Outcome Measure

Increased laminin beta 3 / laminin 332 expression as assessed by immunofluorescence. [ Time Frame: 3 months ]

Central Contacts

• Mei Chen, Ph.D.
  3238650621
  [email protected]
• David Woodley, M.D.
  3238650956
  [email protected]

Locations (1)

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