Though hair on the outer ear may become thicker and more bountiful with age, hair cells in the inner ear—which are necessary for hearing—begin to deteriorate and die. Damage to these hair cells, which can result from disease or chronic exposure to loud noise, is the most common cause of hearing loss. One potential approach to restoring auditory function in the hearing impaired is to replace defective hair cells with healthy cells. In a new study led by John Brigande of the Oregon Health and Science University (Portland), researchers used a gene transfer technique to grow large quantities of functional hair cells in the ears of developing mice, proving that such treatment might eventually be possible.

The scientists used an in utero technique that they had developed to transfer a transcription factor required for hair-cell development (Atoh1) into the inner ears of developing mice (Nature published online 27 August 2008; doi:10.1038/nature07265). Transfected progenitor cells later became incorporated into the organ of Corti, which is located in the cochlea of the inner ear and contains the auditory hair cells. The gene transfer resulted in a substantial increase in the number of auditory hair cells in postnatal mice. Auditory function was normal in 1-month-old mice that underwent the in utero procedure.

Hair cells in the organ of Corti work by converting mechanical stimuli (sound vibrations) into electrical signals that are relayed to the auditory brainstem and the auditory cortex. To test whether transfected hair cells could function like normal cells, the researchers used an electric current to stimulate hair cell bundles in the tissue of newborn mice. Hair cells that were induced by Atoh1 misexpression (identified by a green fluorescent protein marker) had the same electrophysiological properties as did hair cells that grew from normal progenitor cells.

Previous studies have shown that additional hair cells can be induced by gene transfer, but this is the first experiment to prove that such cells are functional. According to Brigande, it remains to be seen whether gene transfer into a deaf mouse would be able to restore the mouse's auditory function. Though the gene therapy technique developed in Brigande's lab is probably only feasible in animals, it may provide valuable insights into the function of Atoh1 and the ability to restore inner ear function through hair cell replacement. Such knowledge is crucial for the development of treatments for human deafness and balance disorders.