Gene Therapy Boosts Deaf Guinea Pigs’ Cochlear Implants
Bolstering cochlear implants with gene therapy may help people with varying degrees of deafness regrow their auditory nerves. Scientists have found a way to get implants to inject genes for a growth factor into the inner ear. The method has already improved the effectiveness of cochlear implants in deaf guinea pigs (real rodents, not metaphorically speaking).
Hearing loss usually occurs with the loss of cochlear hair cells. These specialized cells in the auditory portion of the inner ear help convert acoustic vibrations into electrical impulses — this is the process that allows us to hear sounds. Cochlear implants, which do the work of the hair cells, have been available since the 1970s. They’re considered one of the most successful bionic prostheses, but they can’t restore hearing to normal. “People with cochlear implants do well with understanding speech, but their perception of pitch can be poor, so they often miss out on the joy of music,” Gary Housley of University of New South Wales explains in a news release. This new method could help people with age-related or environmental hearing loss experience sophisticated aspects of sounds, differentiating tonal ranges such as the tinkling of a triangle or the mellow notes of a piano.
By stimulating the regeneration of cochlear nerve cells that help convert frequencies in sound perception, gene therapy could boost the implant’s performance. Specifically, with electro-gene delivery, electrical fields are used to create pores in the cells that line the inner ear, confining gene delivery close to the electrodes in the cochlea.
So, Housley and colleagues from UNSW injected a solution of DNA containing the gene for a growth factor called brain-derived neurotrophic factor (BDNF) into the cochlear implants of completely deaf guinea pigs. Then they used an array of electrodes to fire a few short 20-volt pulses from the implant into the cochlea, transferring the DNA. Within a few hours, cells in the cochlea took up the DNA and started to express neurotrophins — proteins that are crucial for neuron development, function, and even survival.
Previous work has shown that auditory nerve endings regenerate if neurotrophins are delivered to the cochlea. But until now, there hasn’t been a safe way to deliver neurotrophins. According to Housley, no one tried using the cochlear implant itself for gene therapy. He tells Science: “We’ve closed the neural gap.” This image shows the cochlear nerve after neurotrophin gene therapy (top), compared with the untreated cochlea in the same animal (bottom).
The team tested the rodents’ hearing with a common technique used to measure hearing in newborn babies, called the auditory brainstem response test. Electrodes placed on top of the rodents’ heads were used to detect the electricity produced in the brain by excited cochlear nerve fibers in response to sounds. The guinea pigs showed dramatic improvement in hearing — almost to normal levels, although neurotrophin production dropped after a couple months. Housley thinks the problem can be addressed, and the team is getting ready to start a clinical trial with people within two years.
The work was published in Science Translational Medicine this week.
Top image: UNSW Australia Biological Resources Imaging Laboratory and National Imaging Facility of Australia, with T.-T. Hung and A. Kwek, and UNSW Translational Neuroscience Facility, J. Pinyon and G. Housley
Middle image: UNSW Australia Translational Neuroscience Facility, J. Pinyon and G. Housley