Gene therapy restores hearing in deaf animals

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By transferring a gene that regulates fundamental cell development into the inner ear of deafened guinea pigs, researchers have regenerated so-called hair cells and partially restored the animals’ hearing

Hair cells inside the cochlear of the ear respond to sound waves and convert them into electrical nerve signals that the brain interprets as sound. Damaged or absent hair cells are one cause of profound deafness.

To investigate the potential of a gene called Atoh1 to restore hearing in this situation, Dr. Yehoash Raphael, at the University of Michigan in Ann Arbor, and his team first administered ear-damaging drugs to young adult guinea pigs, which led to complete loss of certain hair cells of the cochlea.

Monitoring auditory responses in the brain stem of the animals showed they were profoundly deaf.

The research team then used a modified virus to deliver the Atoh1 gene into the left inner ear of the deafened animals.

Eight weeks later, they saw new hair cells developing in the treated ears, according to a report in the research journal Nature Medicine. In particular, the hair cells looked nearly normal in the innermost part of the ear, although those in the outer structure remained immature.

Brain stem recordings demonstrated improved hearing thresholds at all frequencies, with responses similar to those of normal animals.

“The inner hair cell is the real hearing cell,” Raphael pointed out to Reuters Health. However, outer hair cells are required for distinguishing different sounds, so it is likely the animals’ hearing was distorted.

If similar improvements could be delivered to the human ear, he added, “it would probably improve the threshold in a way that would make many people very happy, but it would still leave the hearing impaired in its quality.”

However, there are several hurdles to be overcome before this technique can be applied to humans. For one thing, the human inner ear is not nearly as accessible as it is in rodents, Raphael pointed out, “so either very complex surgery will have to be designed, or we will have to come up with better vectors or gene delivery methods to deliver the gene.”

SOURCE: Nature Medicine, online February 13, 2005.

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