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An open-label pilot study to assess the safety and effectiveness of Gentamicin given intravenously in people with Recessive dystrophic epidermolysis bullosa (RDEB) with nonsense genetic mutations in COL7A1 in either one or two alleles.
Intravenous administration of Gentamicin restores type VII collagen function and improves wound healing in people with a rare hereditary collagen skin disorder i.e. recessive dystrophic epidermolysis bullosa, which causes skin fragility and scarring starting from birth.
An open-label pilot study to assess the safety and effectiveness of Gentamicin given intravenously in people with Recessive dystrophic epidermolysis bullosa (RDEB) with nonsense genetic mutations in COL7A1 in either one or two alleles.
Two Gentamicin IV regimens between August, 2018-March, 2020 were planned with follow-up through to 180 days. Three patients with RDEB (aged 18 to 28 years) with confirmed nonsense genetic mutations and decreased baseline expression of type VII collagen at the dermoepidermal junction participated in this trial.
All the 3 patients received Gentamicin IV 7.5 mg/kg–1/day for 14 days; out of which, 2 patients received Gentamicin IV at the same dose twice per week for 12 weeks. Exclusion criteria encompassed patients with pre-existing auditory or kidney impairment, existing use of ototoxic or nephrotoxic medicines, or allergy/sensitivities to aminoglycosides or sulfate compounds.
Primary outcomes involved evaluating higher type VII collagen expression in patients' skin and safety evaluations (including ototoxicity, nephrotoxicity, and autoimmune response). The secondary outcomes comprised of assessing wound repair and healing and, using the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) scoring.
After the Gentamicin infusion regimens, skin biopsies from all 3 patients showed increased type VII collagen in their dermoepidermal junction which persisted for at least 6 months after the use of the therapy.
Also, all the wounds under consideration exhibited more than 85% closure at 1 and 3 months. Both Gentamicin regimens lessened the EBDASI total activity scores in all three patients, with a decrease in scores lasting for 3 months even after the treatment. No adverse effects or presence of anti-C7 antibodies were reported.
The use of Gentamicin IV therapy generated the readthrough of nonsense mutations in RDEB patients and promoted the recovery of wounds by mending the functional type VII collagen. This antibiotic therapy may be safe, effective and cost-effective for RDEB patients.
British Journal of Dermatology
Intravenous Gentamicin therapy induces functional type VII collagen in patients with recessive dystrophic epidermolysis bullosa: an open-label clinical trial
David T Woodley et al.
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