Augmenting the ear’s natural defenses

In America, a quarter of people aged 64-75 experience noticeable hearing loss; for those older than 75, half of the population experiences such a disability.

Paul Fuchs, the inaugural David M. Rubenstein Research Professor of Otolaryngology-Head & Neck Surgery, and his team have been working on ways to augment some of the ear’s natural defenses to prevent or reduce such loss.

“The ear talks to the brain through afferent neurons that carry information to the brain and efferent neurons in the brain that project back to the ear. So, this is a feedback pathway,” Fuchs says.

“Activated by sound, efferent neurons provide negative feedback from the brain to regulate the sensitivity of the cochlea, actually protecting the ear from the damaging effects of loud sound,” he explains. “When sound gets louder, they produce stronger negative feedback.”

Through their research, Fuchs and his team have pinpointed a particular molecule that could be altered to increase the strength of this modulation even more and consequently prevent damage, and they are experimenting with gene therapy to create this change. Another possible tool would be treatments through small-molecule pharmacology.

“We are able to study not just the functions, but also the molecules that we think are responsible for those functions by specifically targeting them with antibodies that we can visualize,” according to Fuchs. His team uses electrophysiological methods to record from cells, as well as microscopy and virtual reality to see the cochlea’s 3D structure.

Another project in Fuchs’ lab looks at the causes and possible solutions for hypersensitivity to loud noise – experienced in conditions like tinnitus and hyperacusis – which also occurs once ear tissue has been damaged. This study involves afferent neurons, those carrying signals to the brain that act similar to pain receptor cells.

“The professorship provides resources that can help facilitate or accelerate novel kinds of experiments and allows us to reach out not only within our immediate group of investigators, but more broadly across the university,” he says.

“And we’re at the cusp of applying some of that knowledge to real-world problems, to see how that information can be applied potentially as a therapy,” Fuchs adds in regard to the efferent neurons on the feedback pathway.

In addition to the professorship – the first new professorship in the Department of Otolaryngology-Head & Neck Surgery in 15 years – the $15 million gift from Rubenstein also established the David M. Rubenstein Hearing Center and provides additional research funds.