Clinical Trial: Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title:

Brief Summary: 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, improved RDEB Disease Activity Score, and absence of significant gentamicin side effects.

Detailed Summary:
Sponsor: University of Southern California

Current Primary Outcome:

  • Restoration of full-length type VII collagen as assessed by immunofluorescence. [ Time Frame: 3 months ]
  • Restoration of anchoring fibrils as assessed by transmission electron microscopy. [ Time Frame: 3 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Southern California

Dates:
Date Received: February 19, 2016
Date Started: February 2016
Date Completion: December 2017
Last Updated: April 10, 2017
Last Verified: April 2017