A Hope for Hearing Loss

Technologies for regenerating damaged cells could one day help aging iPod addicts – who are at higher risk of hearing loss.

One of the most common complaints of aging is hearing loss. As we age and our ears are exposed to ever-increasing amounts of loud music and the lawnmower’s roar, the sensitive hair cells in the inner ear are gradually lost.

Researchers at Sound Pharmaceuticals in Seattle, WA are developing new ways to regenerate those hairs – techniques they hope one day might become a treatment for restoring even profound hearing loss.

When a sound wave reaches the ear, it is transmitted to a structure in the inner ear called the cochlea. The vibrations cause hair cells within the cochlea to move, which in turn triggers electrical signals in the auditory nerve that are ultimately interpreted by the brain. People lose sensitive hair cells both with aging and with repeated exposure to loud sounds.

Nowadays cochlear implants, which stimulate the auditory nerve, and hearing aids, which amplify sounds, can help people with serious hearing problems. “But it would be far better to fix what’s biologically broken – to replace hair cells that are lost with new hair cells that would hopefully rewire and transmit signals to the brain,” says James Battey, director of the National Institute on Deafness and other Communication Disorders, part of the National Institutes of Health in Bethesda, MD.

Certain animals, such as birds and fish, can regenerate hair cells; but, for some unknown reason, mammals have lost this capability. In the last few years, scientists have discovered that certain molecules that determine when a cell divides seem to inhibit the regeneration of hair cells in the inner ear. And they’ve found that blocking these molecules can lead to the growth of new hair cells, a discovery that researchers at Sound Pharmaceuticals are developing into a treatment for hearing loss.

The company won a grant last December from the national Defense Advanced Research Projects Agency (DARPA) to support the project. “One of their focuses is to develop strategies to restore hearing in those with severe to profound hearing loss,” says Jonathan Kil, president and CEO of Sound Pharmaceuticals. “Unfortunately, there are lots of young and middle-aged military personnel with this problem, who will have even more profound hearing loss as they age.”

Kil and his team are targeting a cell-cycle regulator, called p27, which suppresses cell division and is expressed in support cells of the inner ear. The researchers designed a way to block the expression of this gene using antisense oligonucleotides – short sequences of DNA that bind to a section of the gene of interest, thereby preventing gene expression. Mice who were given the treatment, which was delivered using injections to the cochlea, showed new cell growth in the ear. According to Kil, support cells take up the DNA and then re-enter the cell cycle, dividing to produce both hair cells and more support cells.

“I think it’s a great approach,” says Yehoash Raphael, an inner-ear biologist at the University of Michigan in Ann Arbor, who is also developing ways to regenerate hair cells. Raphael’s group has had some success using gene therapy to convert other cells in the inner ear into hair cells. But he says ultimately it may be necessary to increase the number of cells in the inner ear, as Kil’s group has done, rather than converting existing cells. Other scientists are studying other cell-cycle regulators with similar properties.

NIH’s Battey also says the approach is promising, but cautions that for effective hearing-loss treatment, “just bringing hair cells back isn’t enough, they must be wired correctly.” They have to form proper connections, he says, so the central nervous system will interpret their input as meaningful sounds.

In fact, previous research suggests that getting these new hair cells to work properly might be tricky. Some animals genetically engineered to make extra hair cells have no or poor hearing, despite their ability to generate hair cells, says Raphael. “We don’t yet know how to overcome that problem,” he says. In addition, newly generated cells sometimes die.

“It’s the right idea, but [gene expression] needs to be carefully controlled,” says Douglas Cotanche, research director in the Department of Otolaryngology at Children’s Hospital Boston. “You can’t just knock down [the gene]…because the system recognizes that is not normal and cells die.”

While still a long way off, such treatments might be ready by the time the iPod generation reaches its golden years. Experts predict that the high volumes and lengthy durations with typical iPod and MP3 player use will lead to serious hearing loss as today’s young adults age. “I don’t believe new treatment is right around the corner,” says Battey, “but our children might benefit from hair-cell regeneration to replace lost cells.”

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