Gene therapy restores hearing in deaf mice

Scientists have used gene therapy to restore hearing in deaf mice, allowing them to detect noise as low as a whisper, an advance that may pave the way for new treatments in humans.
In previous research, scientists had restored rudimentary hearing in genetically deaf mice using gene therapy.
Using an improved gene therapy vector, scientists were success fuk in restoring a much higher level of hearing - down to 25 decibels, the equivalent of a whisper.
While previous vectors have only been able to penetrate the cochlea's inner hair cells, researchers showed that a new synthetic vector, Anc80, safely transferred genes to the hard-to-reach outer hair cells when introduced into the cochlea.

"We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear," said Konstantina Stankovic, associate professor at Harvard Medical School in the US.
"With more than 100 genes already known to cause deafness in humans, there are many patients who may eventually benefit from this technology," said Stankovic.

Researchers used Anc80 to deliver a specific corrected gene in a mouse model of Usher syndrome, the most common genetic form of deaf-blindness that also impairs balance function.
"Outer hair cells amplify sound, allowing inner hair cells to send a stronger signal to the brain. We now have a system that works well and rescues auditory and vestibular function to a level that's never been achieved before," said Gwenaelle Geleoc, from Boston Children's Hospital in the US.

Researchers studied mice with a mutation in Ush1c, the same mutation that causes Usher type 1c in humans. The mutation causes a protein called harmonin to be nonfunctional.
As a result, the sensory hair cell bundles that receive sound and signal the brain deteriorate and become disorganized, leading to profound hearing loss.
When a corrected Ush1c gene was introduced into the inner ears of the mice, the inner and outer hair cells in the cochlea began to produce normal full-length harmonin.
The hair cells formed normal bundles (see images) that responded to sound waves and signaled the brain, as measured by electrical recordings.

Most importantly, deaf mice treated soon after birth began to hear. Geleoc and colleagues showed this first in a "startle box," which detects whether a mouse jumps in response to sudden loud sounds.
When they next measured responses in the auditory regions of the brain, a more sensitive test, the mice responded to much quieter sounds: 19 of 25 mice heard sounds quieter than 80 decibels, and a few could heard sounds as soft as 25-30 decibels, like normal mice.
"Anything that could stabilise or improve native hearing at an early age would give a huge boost to a child's ability to learn and use spoken language," said Margaret Kenna, from Boston Children's.

The study was published in the journal Nature Biotechnology.