Clinical Trial: Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa Patients With Nonsense Mutations

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title:

Brief Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited skin disease caused by mutations in the COL7A1 gene that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs), structures that mediate epidermal-dermal adherence. Thirty percent of RDEB patients have nonsense mutations. The investigators recently demonstrated in 5 such patients that intradermal and topical gentamicin induced "read-through" of their nonsense mutations and created robust and sustained new C7 and AFs at the dermal-epidermal junction (DEJ) of their skin and also stimulated wound closure and reduced new blister formation. No untoward side effects occurred. Herein, the investigators propose evaluating the safety and efficacy of intravenous gentamicin in these patients. In theory, this intravenous administration has the possibility of treating simultaneously all of the patients' skin wounds. The investigators also propose optimizing the concentration and manner of delivery of topical gentamicin. The unambiguous milestones will be increased C7 and AFs in the patients' DEJ, improved EB Disease Activity Scores, and absence of significant gentamicin side effects.

Detailed Summary:
Sponsor: University of Southern California

Current Primary Outcome:

  • Increased expression of full-length type VII collagen as assessed by immunofluorescence [ Time Frame: 6 months ]
  • Generation of new anchoring fibrils as assessed by immuno-electron microscopy [ Time Frame: 6 months ]
  • Absence of gentamicin side effects especially the detection of any ototoxicity or nephrotoxicity [ Time Frame: 6 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome: Improved epidermolysis bullosa Disease Activity Scores [ Time Frame: 6 months ]

Original Secondary Outcome: Same as current

Information By: University of Southern California

Dates:
Date Received: January 4, 2017
Date Started: January 2017
Date Completion:
Last Updated: January 5, 2017
Last Verified: January 2017