A Pitt scientist is striving to quiet the ringing in veterans' ears

You may have experienced it: You come home from a loud concert, and a faint ringing noise in your ears comes home with you. It probably faded after a few hours. But for more than 2 million U.S. veterans, the sound never goes away.

“There is something, a sound, that you keep hearing,” said Thanos Tzounopoulos, professor and vice chair of research in Pitt’s Department of Otolaryngology in the School of Medicine. “Only you can hear it, it doesn't exist in the outside world.”

Tinnitus, hearing a persistent ringing, hissing or buzzing noise, is the most common service-related disability in U.S. veterans, who are exposed to a wide variety of loud noises that can trigger the disorder. Despite how widespread tinnitus is, there’s no FDA-approved cure — but Tzounopoulos is well on the way to changing that.

Part of why the search for a treatment has taken so long, Tzounopoulos said, is because for years scientists mistakenly thought the noises heard by those with tinnitus come from the ear.

“Tinnitus starts with the ear, but it’s the brain that maintains it,” said Tzounopoulos, who also directs the Pittsburgh Hearing Research Center. “It usually starts with some sort of hearing loss, and the brain is trying to compensate to deal with the new reality.”

Usually, the brain filters out signals that aren’t relevant. In 2011, Tzounopoulos found that tinnitus can occur when exposure to loud noises stops one of those filters from working. Another way of thinking about it is that your brain has built-in gates that only let in sounds from the outside, while keeping out noise that the brain itself generates. For those with tinnitus, the gatekeepers are off duty for good.

A 2013 Pitt Medcast episode described Tzounopoulos’ research as a “promising path,” and the eight years since have borne that prediction out. In 2015, Tzounopoulos partnered with Peter Wipf, a distinguished professor of chemistry in the Kenneth P. Dietrich School of Arts and Sciences, to begin developing drugs that could target the specific mechanism he identified as a trigger for tinnitus. “We’re trying to quiet down the first stop of the auditory nerve in the brain,” Tzounopoulos said.

The drug they’ve been focusing on, called RL-81, would be used soon after tinnitus develops, and recent research indicates it could remain effective much longer than they first expected. Their testing shows great promise in preventing mice from developing tinnitus after being exposed to loud noises. Since then, the group has been refining their approach, searching for ways to make those potential drugs safer and more effective, and the treatment is now in preclinical testing to prepare for future human trials.

There’s no shortage of patients waiting for a treatment — more than 50 million Americans experience tinnitus. While the condition might not sound so bad to those who don’t experience it, for those with a severe case, it can be debilitating and often goes hand in hand with sleep disorders, anxiety and depression. Methods for helping those suffering from tinnitus usually target patients’ emotional response to the condition rather than treating the cause of the noise itself.

The military is especially invested in discovering treatments because of the disproportionate number of veterans who experience tinnitus. Tzounopoulos has received more than $4 million in funding from the Department of Defense since 2009 to understand what causes the condition and to search for potential cures. “I’m grateful to the veterans and the Department of Defense,” he said. “A lot of our progress comes from their support.” His work is also supported by the Pittsburgh Eye and Ear Foundation, Pitt’s School of Medicine and UPMC.

While moving toward a treatment, Tzounopoulos has also harbored an interest in the many ways tinnitus can occur in different people: Some people appear to be more resilient to the condition, and it can also be triggered by things other than loud noises.

Hearing a noise, he said, isn’t as simple as it sounds. “Perception is an emergent property: There are a lot of networks that have to come together to give rise to what we hear, what we see, what we smell.”

Researchers have identified three distinct brain networks that may be involved in tinnitus, and damage to each of them may require different treatments. So, in the future, treating the condition may involve scanning an individual’s brain to understand the neurobiological origin of their specific condition. “Then we can have a precision medicine approach and facilitate whatever the individual needs,” Tzounopoulos said.

The past decade has seen unprecedented progress in the battle to understand how the condition forms and how it might be prevented. As for the future, Tzounopoulos is confident that the days of tinnitus being a disease without a treatment are numbered.

“We have a clear path: We are committed, and we’ll keep going at it,” he said. “It’s hard to predict how fast you’re going to solve a problem, but I can tell you they’re solvable problems.”

— Patrick Monahan, photo by Joshua Franzos