Gentamicin may restore missing skin proteins and improve wound healing in patients with inherited epidermolysis bullosa caused by nonsense mutations, but Aussie researchers say it’s still early days.
A decades-old antibiotic best known for treating serious bacterial infections may have an unexpected role in dermatology, with a new systematic review finding gentamicin shows encouraging signs of improving wound healing in patients with rare inherited forms of epidermolysis bullosa (EB).
Researchers from Sydney Children’s Hospital, UNSW Sydney, and the University of Sydney reviewed all published interventional clinical trials investigating gentamicin as a treatment for junctional and dystrophic EB.
They concluded that while the evidence remained preliminary, the therapy consistently restored expression of critical structural skin proteins and was associated with improved wound healing in most patients.
The review, published in the Australasian Journal of Dermatology included five clinical trials involving 24 patients aged from three months to 31 years.
Nineteen patients had confirmed nonsense mutations, a type of genetic variant that introduces a premature stop codon and prevents production of full-length proteins essential for maintaining skin integrity.
Gentamicin was administered in a variety of ways, including topical ointment, intravenous infusion, and intradermal injection.
Unlike its conventional use as an antibiotic, gentamicin’s therapeutic effect in EB relied on its ability to induce “premature termination codons”, the researchers said.
“Gentamicin is thought to induce PTCs readthrough by binding to mammalian ribosomal RNA, which disrupts the codon-anticodon recognition at the amino-acyl-tRNA acceptor A site,” they wrote.
“The disruption bypasses PTC, thereby leading to more functional proteins. Gentamicin has been shown to improve the ocular surface disease index and decrease plaque and gingival bleeding in JEB and RDEB, respectively.
“Systemic gentamicin demonstrated improvement in skin, respiratory, and neuromuscular manifestations in a patient with EB simplex with muscular dystrophy.
“Gentamicin can also be effective intramuscularly. No adverse outcomes were observed in any of these studies.”
All five studies demonstrated increased expression of either collagen VII or laminin-332 on skin biopsy following treatment.
In one study of recessive dystrophic EB, collagen VII fluorescence increased by almost 96%, with patients carrying nonsense mutations experiencing substantially greater increases than those without confirmed mutations. Other studies reported collagen or laminin expression increasing by around 50-75%, with effects persisting for up to six months after treatment.
Clinical outcomes were more variable because each study used different measures of wound healing. Nevertheless, four of the five trials reported improvements.
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One topical gentamicin study involving children with severe junctional EB found all treated erosions had either closed or reduced in size after one month and achieved complete closure by three months.
Another intravenous study found all monitored wounds achieved at least 85% closure after one and three months of treatment, although only half maintained that level of healing at six months.
Several studies also measured disease severity using the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). Patients generally experienced reductions in disease activity scores following treatment, although improvements were not always sustained over longer follow-up.
None of the 24 patients experienced treatment-related adverse events. Studies specifically monitored for the aminoglycoside toxicities that have historically limited gentamicin use, including hearing loss and kidney injury, but detected neither.
The researchers also found no evidence that treatment triggered autoimmune responses against collagen VII or laminin-332.
Despite these promising findings, the researchers urged caution in interpreting the results.
Four of the five studies were open-label and lacked control groups, placing them at serious risk of bias according to the ROBINS-I assessment tool.
The only placebo-controlled study included just five patients, while differences in dosing schedules, treatment duration, routes of administration and outcome measures made it impossible to pool the data in a meta-analysis.
The researchers also noted that most studies focused on laboratory evidence of restored protein expression rather than patient-centred outcomes.
None assessed health-related quality of life despite the profound physical and psychological burden associated with EB. Future trials should include validated clinical scoring systems alongside patient-reported outcome measures, they said.
The findings come as the treatment landscape for EB continues to evolve.
The researchers noted that the topical gene therapy beremagene geperpavec (Vyjuvek) had demonstrated complete wound healing in 67% of treated wounds after six months compared with 22% of placebo-treated wounds and received European approval in 2025 for dystrophic EB caused by COL7A1 mutations.
However, they said that gentamicin could retain an important role because it was inexpensive, widely available and may offer a more accessible option in settings where gene therapies remain prohibitively expensive.
The researchers concluded that gentamicin-induced readthrough therapy has the potential to restore structural protein expression and deliver meaningful clinical benefit for patients with EB caused by nonsense mutations.
“For lifelong conditions like EB that may require long-term, intermittent dosing, clinicians should be aware of possible cumulative toxicity and implement appropriate monitoring,” they wrote.
“Well-designed, adequately powered clinical trials incorporating validated clinical endpoints and longer-term safety assessment are required to establish the role of gentamicin in the therapeutic armamentarium for epidermolysis bullosa.”
