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Purpose

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.

Condition

Eligibility

Eligible Ages
All ages
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. JEB patients with nonsense mutations in the LAMB3 gene in either one or two alleles.

Exclusion Criteria

  1. JEB patients who do not have nonsense mutations in the LAMB3 gene in either allele. 2. Pre-existing known auditory impairment. 3. Pre-existing known renal impairment. 4. Pre-existing known allergies to aminoglycosides or sulfate compounds. 5. Pregnancy.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Gentamicin Sulfate
    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.
    Other names:
    • Gentamicin

Recruiting Locations

University of Southern California
Los Angeles 5368361, California 5332921 90033
Contact:
David Woodley, MD
323-865-0956
dwoodley@usc.edu

More Details

Status
Recruiting
Sponsor
University of Southern California

Study Contact

Mei Chen, Ph.D.
3238650621
chenm@usc.edu

Detailed Description

Three subjects (adults and children of any age) will receive topical gentamicin to be applied to select skin sites. Three subjects (adults and children of any age) will receive intravenous (IV) gentamicin infusions. Patients will be assessed for Primary and Secondary endpoints during follow up visits.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.