Sci. Aging Knowl. Environ., 16 February 2005
Vol. 2005, Issue 7, p. nf13
[DOI: 10.1126/sageke.2005.7.nf13]


Now Hear This

Gene therapy alleviates deafness in rodents

Mitch Leslie

Like the understudy who backs up the veteran star of a Broadway musical, some ear cells are ready to replace the sound-sensing cells that falter with age. All they need is the right stimulation, a new study suggests. The work shows that gene therapy induces deaf animals to spawn new sound-sensitive cells. The technique could eventually lead to remedies for age-related hearing loss.

The sound-detecting hair cells in the cochlea of the inner ear perish as we grow old, and certain drugs, diseases, and loud encores of "Freebird" can speed their demise. The ear doesn't replace the cells, so deafness results if enough die. A cochlear implant, an electronic device that surgeons insert behind the ear, can improve sound reception, but researchers hope to discover how to rejuvenate hair cells and restore hearing. Inner ear biologist Yehoash Raphael of the University of Michigan Medical School in Ann Arbor and colleagues hypothesized that gene therapy could help. Two years ago, they showed that doses of the Atoh1 gene, which spurs inner ear cells to specialize, prodded guinea pigs to make new hair cells. In the new work, the team wanted to test whether nurturing hair cells would revive hearing in deaf rodents.

They first deafened guinea pigs with doses of two drugs, an antibiotic and a high-blood-pressure pill. When they dissected the inner ears of some animals shortly after the treatment, the researchers saw no hair cells. Their absence eliminates the possibility that any cells found after gene therapy were stragglers that had survived the drugs. Next, the researchers injected a virus carrying Atoh1 into some rodents' left inner ears. Other animals received empty viruses, and the rodents' right cochleas served as controls. The team gauged the rodents' hearing and then dissected their inner ears. After 8 weeks, cochleas from guinea pigs that had received Atoh1 infusions bristled with hair cells, which were absent from animals that got dud viruses and from the rodents' right cochleas. Confirming their identity, the new cells pumped out a protein unique to hair cells. Tests showed that the animals' right ears remained deaf, but hearing returned in the left ears of animals treated with Atoh1--and some nearly reached normal sensitivity. Atoh1 likely works by goading the supporting cells that cradle hair cells to transform, says Raphael. The animals probably didn't regain normal sound perception, he cautions, because the hair cells that amplify sounds and sharpen hearing often hadn't developed fully.

"They document quite clearly that they have new hair cells" in the portion of the inner ear that senses sounds, says neuroscientist Douglas Cotanche of Harvard Medical School in Boston. Further research should delve into how well the animals discern different pitches and whether hearing can rebound even when a long time elapses between deafness and treatment, he says. Another key issue is whether gene therapy eases deafness caused by other factors, such as old age or loud sounds, says Raphael. Answering these questions might help researchers discover the best way to give the supporting cells their big break.

February 16, 2005
  1. M. Izumikawa et al., Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat. Med., 13 February 2005 [e-pub ahead of print]. doi:10.1038/nm1193
Citation: M. Leslie, Now Hear This. Sci. Aging Knowl. Environ. 2005 (7), nf13 (2005).

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