Can We Unlock The Body's Ability To Regenerate Lost Hearing?

When a middle-aged firefighter and active Boy Scout leader in the Midwestern United States lost his hearing a few years ago, he also faced the loss of his livelihood. Noise and toxin exposures had damaged the tiny sound-sensing hair cells of his inner ear, leaving him with severe hearing loss. To keep working, he opted for the only available option: cochlear implants, microphones mounted behind the ear that transmit sounds to electrodes implanted in the inner ear, bypassing the hair cells to create an electronic approximation of natural hearing.

For new patients with similar hearing loss, however, an exciting option is on the horizon. In May 2014, an experimental drug from Novartis that could potentially restore lost hearing entered early-phase clinical trials. Rather than providing an electronic solution, the drug appears to unlock the body’s ability to regenerate delicate hair cells and repair the ear’s natural auditory mechanics. Much research remains to be done, but if the experimental drug, known by its research designation CGF166, proves effective and safe in this trial, it could lead to a major breakthrough for the treatment of hearing loss.

“This is a very novel attempt to develop a medication targeted at an important inner ear disease,” says Hinrich Staecker, head and neck surgeon at the University of Kansas Medical Center in the USA and the principal investigator for the trial. “We have a lot of workarounds for hearing loss, but it still takes a tremendous toll on day-to-day life.”

Hearing loss can be frustrating, isolating, and disabling -- suffering that is evident from the reaction Staecker received after the trial’s launch. Following coverage of the clinical study in the magazine New Scientist in April 2014 he received more than 600 emails and dozens of daily phone calls from potential patients.

Where Need Meets Science

This is a very novel attempt to develop a medication targeted at an important inner ear diseaseHinrich Staecker, head and neck surgeon, University of Kansas Medical Center, US.

Disabling hearing loss affects 360 million individuals globally and about a third of people over the age of 65, according to the World Health Organization. In the US, nearly half of those over age 75 suffer significant hearing loss. Despite this need, people have few options. “There are devices, but no drugs for hearing loss,” says Lloyd Klickstein, head of translational medicine for the New Indications Discovery Unit at the Novartis Institutes for BioMedical Research, who guided the advancement of the new therapy.

In 2009, Klickstein and his team were charged with identifying new opportunities for Novartis, focusing on conditions that are well understood scientifically, yet have few treatment options. Of 6,000 conditions he and his colleagues surveyed, “diseases of hearing and balance bubbled to the top,” he says. The team asked the Novartis Strategic Alliances group to help find partnership opportunities in academia or among biotech companies.

While the medical need was clear, the science also was compelling. In 1999, scientists had singled out atonal, a gene that acts as a “master switch” for turning on the growth of inner ear hair cells, which pick up sound waves and translate them into electrical signals in the brain. Humans are born with hair cells, but the atonal switch flips off at birth. Any subsequent damage to hair cells is permanent. In contrast, birds are able to replace lost hair cells.

Lloyd Klickstein and Susan Stevenson: gene therapy may lead to a potential treatment for hearing lossLloyd Klickstein and Susan Stevenson: gene therapy may lead to a potential treatment for hearing loss.

Acting on this discovery, a biotech company called GenVec developed a way to flip that switch back on. They used a viral vector, a virus that has been altered with the aim of making it harmless so it can act as a carrying case for atonal. The virus carries the atonal gene into the cells that line the insides of the snail-shaped cochlea, some of which are capable of turning into hair cells. In these cells, atonal appears to cue that transformation. The newly formed hair cells then wire themselves into the part of the brain that processes sound.

Working with academic labs, GenVec researchers showed in 2005 that their vector carrying the mouse version of the gene could restore hearing in deafened rodents. Later, in 2011, scientists showed that this drug also restored balance in rodents.
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