Protecting auditory nerve cells using genetic therapy
Sensorineural hearing loss is caused by damage to the sensory hair cells and auditory neurons in the inner ear. The application of nerve survival factors, known as neurotrophic factors, to the deaf cochlea prevents the degeneration of auditory neurons which occurs following the loss of the hair cells. Neurotrophic factors also stimulate the regrowth of auditory nerve fibres although the pattern of regrowth does not resemble a normal cochlea.
To enhance and maintain the surviving auditory neurons in deaf cochlear implant (CI) recipients, we are researching methods to deliver neurotrophic factors into the cochlea in a variety of ways.
These types of studies have important potential for clinical applications because we envisage a next generation of CIs that can actively deliver drugs which can either preserve residual hearing or prevent further degeneration of primary auditory neurons.
In addition, these techniques may be eventually applied to implants in other parts of the nervous system, such as the retina of the eye.
The purpose of this work is to preserve or regenerate the highly structured neural organisation of the cochlea using gene therapy techniques.
We previously discovered that flooding the cochlea with neurotrophic factors protected auditory neurons after deafness, but we noticed that the nerve fibres grew abnormally which could result in a confusing sound perception with a cochlear implant. Using clues from the normal development of the inner ear, we proposed that a more localised source of neurotrophic factors will provide the neurons with survival signals as well as directional cues to guide their growth to the right location.
Gene therapy techniques allow the cochlea’s own cells to produce neurotrophic factors just as hair cells and supporting cells would normally do. This study provides the first steps towards controlling nerve growth in the cochlea after hearing loss.
If we can achieve long-term nerve survival and controlled re-growth of nerve fibres after hearing loss, then we can potentially improve CI performance.
NHMRC, Action on Hearing Loss (UK), The Garnett Passe and Rodney Williams Memorial Foundation