New hope for people with sound-induced deafness

By Helen Albert, Senior medwireNews Reporter

Preliminary results from a study in mice suggest it may be possible to regenerate cochlear hair cells that have been damaged due to excessive noise exposure.

A team of investigators, led by Albert Edge (University of Harvard, Boston, Massachusetts, USA), managed to induce partial hearing recovery in mice with noise-induced deafness by chemically modifying stem cells from the cochlea region.

"These cells, called supporting cells, transdifferentiate into hair cells after inhibition of the Notch signaling pathway, and the new hair cell generation results in a recovery of hearing in the region of the cochlea where the new hair cells appear," explained Edge in a press statement.

The researchers discovered that Notch signaling could be inhibited in inner ear stem cells in vitro by a γ-secretase inhibitor (LY411575). The resulting increase in levels of the transcription factor, Atoh1, essential for inner ear hair cell formation, resulted in transformation of the stem cells into cochlear hair cells.

The team then tested whether LY411575, injected directly into the inner ear via the round window membrane, could restore noise-induced hearing loss in vivo in a mouse model. Control mice with noise-induced deafness that were treated with a placebo were also monitored for comparison purposes.

After 1 month the researchers observed new hair cell growth in the cochlea of mice treated with LY411575, aided by green fluorescent protein marking of the relevant cells, but not in control animals.

At 3 months, the number of outer hair cells had increased throughout the center of the cochlea in mice treated with LY411575 compared with controls.

The auditory brainstem response was used to test the hearing ability of the mice. No improvement was seen in the control mice, but responses were significantly improved in LY411575-treated mice at 8.0, 11.3, and 16.0 kHz, but not at frequencies above 22.7 kHz.

"Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness," write the researchers in Neuron, although they concede that more research is needed before this method can be tested in humans.

"The significance of this study is that hearing loss is a huge problem affecting 250 million worldwide," concluded Edge.

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