Background
The ‘Cochlear Implant Neurotrophin Gene Therapy’ (CINGT) trial is a first-in-human clinical trial to investigate the safety and efficacy of neurotrophin gene augmentation during cochlear implant surgery to ‘close the neural gap’ in people with hearing loss.
The ‘neural gap’ reflects the separation of the auditory neurons in the cochlea from the cochlear implant (CI) electrodes, where the ability of the CI to selectively stimulate small groups of these neurons, and thereby provide high fidelity hearing, is limited by the spread of current from the electrodes.
This gene therapy treatment uses precision delivery of DNA encoding neurotrophins, which cause local directed regrowth of the nerve fibres towards the CI electrodes, so that more discrete stimulation can be achieved.
The first patient was recruited into the CINGT study in August 2020, and by the close of the study in June 2024, 17 patients had received the gene therapy during their cochlear implant surgery at the Royal Prince Alfred Hospital in Sydney, Australia.
How is the neurotrophin gene therapy delivered?
While the study was exploratory, it confirmed the safety of delivering ‘naked’ DNA encoding therapeutic proteins (brain-derived neurotrophic factor and neurotrophin-3) into the cochlea using a modified CI electrode array engineered to act as an ‘electro-lens’ so that electrical pulses similar to the normal electrical stimulation provided by a CI was able to steer the therapeutic DNA to cells close to where the permanently implanted CI was positioned.
This DNA delivery technology is called BaDGE® (Bionic array – Directed Gene Electrotransfer); developed by neuroscientists and biomedical engineers from the University of New South Wales (UNSW) Sydney. UNSW was the host institution for the CINGT clinical trial.
To find out more about BaDGE® please visit:
Study design
Participants are recruited into two groups:
Control group: this group receives a normal cochlear implant system. It allows us to establish what happens in patients receiving the cochlear implant alone without the additional gene therapy in order to compare with the other group.
Treatment group: this group receives the neurotrophin gene therapy during cochlear implant surgery. This is an investigational treatment for people with hearing loss, which means that it is not an approved procedure in Australia and must be tested to see if it is an effective treatment.
Both groups of participants are asked to attend 11 visits over a 52-week period where they would undergo a series of assessments to monitor the safety and efficacy of the treatment. The assessments included: Clinical and psychoacoustic measures, electrophysiological measures and safety measures.
Study findings
The CINGT study has been a great success. Firstly, we can report that there were no adverse reactions from the BaDGE® procedure. All the trial participants (those receiving the neurotrophin gene therapy and control group subjects who underwent routine CI surgery) had good hearing outcomes.
By diving into subjective and objective measures of this hearing across 9 post-operative visits, we found that hearing outcomes were very stable and many of the gene therapy treatment group showed evidence of very acute hearing with the CI device.
To date the provisional findings of the study have been presented at a number of professional conferences by the program leaders, and the primary publications will be published shortly.
Registrations and approvals
Registered on the Australian New Zealand Clinical Trial Registry, with UNSW Sydney as the Host Institution (ACTRN12618001556235).
Registered through the Australian Therapeutic Goods Administration as combination Medical Device and Drug trial.
Reviewed and approved by the Sydney Local Health District (RPAH Zone) Human Research Ethics Committee.
Institutional partners
