A Potential New Way to Prevent Noise-Induced Hearing Loss: Trapping Excess Zinc

Posted on February 22nd, 2024 by Dr. Monica M. Bertagnolli

Hearing loss is a pervasive problem, affecting one in eight people aged 12 and up in the U.S.¹ While hearing loss has multiple causes, an important one for millions of people is exposure to loud noises, which can lead to gradual hearing loss, or people can lose their hearing all at once. The only methods used to prevent noise-induced hearing loss today are avoiding loud noises altogether or wearing earplugs or other protective devices during loud activities. But findings from an intriguing new NIH-supported study exploring the underlying causes of this form of hearing loss suggest it may be possible to protect hearing in a different way: with treatments targeting excess and damaging levels of zinc in the inner ear.

The new findings, reported in the Proceedings of the National Academy of Sciences, come from a team led by Thanos Tzounopoulos, Amantha Thathiah, and Chris Cunningham, at the University of Pittsburgh.² The research team is focused on understanding how hearing works, as well as developing ways to treat hearing loss and tinnitus (the perception of sound, like ringing or buzzing, that doesn’t have an external source), which both can arise from loud noises.

Previous studies have shown that traumatic noises of varying durations and intensities can lead to different types of damage to cells in the cochlea, the fluid-filled cavity in the inner ear that plays an essential role in hearing. For instance, in mouse studies, noise equivalent to a blasting rock concert caused the loss of tiny sound-detecting hair cells and essential supporting cells in the cochlea, leading to hearing loss. Milder noises comparable to the sound of a hand drill can lead to subtler hearing loss, as essential connections, or synapses, between hair cells and sensory neurons are lost.

To better understand why this happens, the research team wanted to investigate the underlying cellular- and molecular-level events and signals responsible for inner ear damage and irreversible hearing loss caused by loud sounds. They looked to zinc, an essential mineral in our diets that plays many important roles in the body. Interestingly, zinc concentrations in the inner ear are highest of any organ or tissue in the body. But, despite this, the role of zinc in the cochlea and its effects on hearing and hearing loss hadn’t been studied in detail.

Most zinc in the body—about 90%—is bound to proteins. But the researchers were interested in the approximately 10% of zinc that’s free-floating, due to its important role in signaling in the brain and other parts of the nervous system. They wanted to find out what happens to the high concentrations of zinc in the mouse cochlea after traumatic levels of noise, and whether targeting zinc might influence inner ear damage associated with hearing loss.

The researchers found that, hours after mice were exposed to loud noise, zinc levels in the inner ear spiked and were dysregulated in the hair cells and in key parts of the cochlea, with significant changes to their location inside cells. Those changes in zinc were associated with cellular damage and disrupted communication between sensory cells in the inner ear.

The good news is that this discovery suggested a possible solution: inner ear damage and hearing loss might be averted by targeting excess zinc. And their subsequent findings suggest that it works. Studies in mice that were treated with a slow-releasing compound in the inner ear were protected from noise-induced damage and associated hearing loss. The treatment involves a chemical compound known as a zinc chelating agent, which binds and traps excess free zinc, thus limiting cochlear damage and hearing loss.

Will this strategy work in people? We don’t know yet. However, the researchers report that they’re planning to pursue preclinical safety studies of the new treatment approach. Their hope is to one day make a zinc-targeted treatment readily available to protect against noise-induced hearing loss. But, for now, the best way to protect your hearing while working with noisy power tools or attending a rock concert is to remember your ear protection.

References:

[1] Quick Statistics About Hearing. National Institute on Deafness and Other Communication Disorders.

[2] Bizup B, et al. Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery. PNAS. DOI: 10.1073/pnas.2310561121 (2024).

NIH Support: National Institute on Deafness and Other Communication Disorders, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering