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MADISON – Otolaryngologist Dr. Samuel Gubbels is one step closer to realizing a dream: treating patients who have lost their hearing by regenerating the damaged inner-ear cells that are at the heart of hearing.
Gubbels, an assistant professor of surgery at UW School of Medicine and Public Health, and collaborators at Oregon Health and Science University (OHSU) and Stanford recently completed a study in which they grew the specialized "hair cells" necessary for hearing by transferring a primary gene responsible for hair-cell formation into the inner ear of mice embryos.
The findings are reported in this week's edition of the journal Nature.
Unlike previous studies, this study was the first to show that introducing the gene Atoh 1 in utero early in development produced hair cells that work normally by several electrophysiological and biophysical measures. The hair cells also made rudimentary connections with central nervous system cells critical to hearing, and they displayed an ability to transmit signals mechanically, further evidence that they were true, functioning hair cells.
The findings represent tantalizing advances for otolaryngologists and audiology researchers studying the potential of regenerative medicine to treat hearing disorders.
"Most forms of hearing loss and some forms of balance disorders are characterized by a loss of hair cells in the inner ear," says Gubbels, adding that genetic defects can often be the source of the problem. "Aside from using hearing aids and cochlear implants, we have been plagued with an inability to restore hearing because it's very difficult for hair cells to regenerate."
The new findings will help scientists better understand how hair cells form. And the in utero gene transfer technique the researchers developed offers promise as a viable new approach to investigating the regenerative process.
"The ability to conduct experiments in the developing mammalian ear by gene transfer in utero should permit us to design and assess gene therapies aimed at ameliorating hearing loss and vestibular function in mouse models of human deafness and balance disorders," says Gubbels. "This is an important step in defining regenerative approaches to treat inner-ear disease in humans."
The ultimate goal, says Gubbels, would be to introduce a gene or medication to the deaf ear that would result in growth of functioning hair cells and restoration of hearing. Another possibility would be to drive stem cells to become hair cells.
Gubbels' collaborators on the study included David Woessner, John Mitchell and John Brigande of OHSU and Anthony Ricci at Stanford.
Gubbels is working with investigators at the UW Waisman Center, conducting ongoing studies on regenerative therapies for hearing loss.

Date Published: 08/29/2008

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