Study points to possible new therapy for hearing loss

Hearing impairment has long been accepted as a fact of life for the aging population.  However, scientists have long observed that other animals — namely birds, frogs, and fish — have been shown to have the ability to regenerate lost sensory hair cells.

“It’s funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration,” said Jingyuan Zhang, Ph.D., with the University of Rochester Department of Biology and a co-author of the study. “We’re the only vertebrates that can’t do it.”

Research conducted in the lab of Patricia White, Ph.D., in 2012 identified a family of receptors — called epidermal growth factor (EGF) — When triggered, these cells proliferate and foster the generation of new sensory hair cells. She speculated that this signaling pathway could potentially be manipulated to produce a similar result in mammals.

“In mice, the cochlea expresses EGF receptors throughout the animal’s life, but they apparently never drive regeneration of hair cells,” said White. “Perhaps during mammalian evolution, there have been changes in the expression of intracellular regulators of EGF receptor family signaling. Those regulators could have altered the outcome of signaling, blocking regeneration. Our research is focused on finding a way switch the pathway temporarily, in order to promote both regeneration of hair cells and their integration with nerve cells, both of which are critical for hearing.”

In the new study, the team tested the theory that signaling from the EGF family of receptors could play a role in cochlear regeneration in mammals. The researchers focused on a specific receptor called ERBB2 which is found in cochlear support cells.

The researchers found that activating the ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to proliferate and start the process of activating other neighboring stem cells to become new sensory hair cells. Furthermore, it appears that this process not only could impact the regeneration of sensory hair cells, but also support their integration with nerve cells.

“The process of repairing hearing is a complex problem and requires a series of cellular events,” said White. “You have to regenerate sensory hair cells and these cells have to function properly and connect with the necessary network of neurons. This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing.”

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