Cochlear Implant Also Uses Gene Therapy to Improve Hearing and electrode triggered gene therapy could improve other machine body connections

The electrodes in a cochlear implant can be used to direct gene therapy and regrow neurons.

The researchers behind the work are investigating whether electrode-triggered gene therapy could improve other machine-body connections—for example, the deep-brain stimulation probes that are used to treat Parkinson’s disease, or retinal prosthetics.

More than 300,000 people worldwide have cochlear implants. The devices are implanted in patients who are profoundly deaf, having lost most or all of the ear’s hair cells, which detect sound waves through mechanical vibrations, and convert those vibrations into electrical signals that are picked up by neurons in the auditory nerve and passed along to the brain. Cochlear implants use up to 22 platinum electrodes to stimulate the auditory nerve; the devices make a tremendous difference for people but they restore only a fraction of normal hearing.

When the ear’s hair cells degrade and die, the associated neurons also degrade and shrink back into the cochlea. So there’s a physical gap between these atrophied neurons and the electrodes in the cochlear implant. Improving the interface between nerves and electrodes should make it possible to use weaker electrical stimulation, opening up the possibility of stimulating multiple parts of the auditory nerve at once, using more electrodes, and improving the overall quality of sound.

Peptides called neurotrophins can encourage regeneration of the neurons in the auditory nerve. Housley used a common process, called electroporation, to cause pores to open up in cells, allowing DNA to get inside. It usually requires high voltages, and it hasn’t found much clinical use, but Housley wanted to see whether the small, distributed electrodes of the cochlear implant could be used to achieve the effect.

Housley’s group used deafened guinea pigs, which are commonly used as a hearing model because their cochleas are similar in size to those found in humans. During surgery to place the cochlear implant, they injected the cochlea with a neurotrophin gene vector. Once the implant was placed, they applied an electroporation voltage using the electrodes. The process, which took only a few seconds during surgery, resulted in nerve regeneration in the animals. And weeks after implantation, the nerves of treated animals showed stronger responses to signals from the implant, which suggests they are able to hear more. This research is described this week in the journal Science Translational Medicine.

Other Gene Therapy Progress

Retinal gene therapy could prevent loss of vision in patients with choroideremia and other retinal diseases, show the results of a phase I/II study.

The researchers report in The Lancet that there were no obvious detrimental effects from the detachment and treatment of the fovea with an adeno-associated viral (AAV) vector encoding the Rab escort protein 1 (REP1).

They explain that choroideremia leads to blindness due to mutations in the CHM gene, which encodes REP1. And while good visual acuity is generally maintained until the degeneration reaches the fovea, identifying underlying changes in retinal activity could indicate the functional effects of gene therapy.

Six male patients aged between 35 and 63 years with choroideremia and null mutations in the CHM gene received up to 1.0×1010 genome particles of AAV.REP1 in one eye by subfoveal injection after surgical retinal detachment, with five eyes receiving the full dose. The participants were also treated with a 10-day course of oral prednisolone.

The overall mean gain in visual acuity was 3.8 letters on the Early Treatment for Diabetic Retinopathy Study (ETDRS) system, report Robert MacLaren (University of Oxford, UK) and colleagues. However, gains were in fact only seen in two patients who had a reduced visual acuity at baseline: one gained 21 letters and one gained 11 letters.

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