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DRUG COMPOUND BLOCKS NOISE-INDUCED HEARING LOSS

Originally published Jun 2020

BY JULIA EVANGELOU STRAIT

The spiral-shaped cochlea of the inner ear is responsible for detecting sound. Inner hair cells lining the cochlea transform the mechanical vibrations of sound waves into chemical signals. These chemicals—primarily one called glutamate—are then released from the hair cells and received by glutamate receptors on auditory nerve fibers. These fibers then send electrical impulses to the brain. There, the signals are interpreted as language, music or signs of danger, for example.

mice cochlea
INNER HAIR CELLS OF THE COCHLEA (GREEN AND BLUE) EXCITE AUDITORY NERVE FIBERS (RED) BY RELEASING GLUTAMATE, A CHEMICAL SIGNAL THAT HELPS CONVERT SOUND WAVES INTO ELECTRICAL SIGNALS THAT TRAVEL TO THE BRAIN. BUT TOO MUCH GLUTAMATE CAN BE HARMFUL, LEADING TO NOISE-INDUCED HEARING LOSS.
Photo by Aizen Yang-Hood, MD

The junction between a hair cell and a nerve fiber is called a synapse. Loud noise can release too much glutamate, overwhelming the glutamate receptors, which leads to loss of synapses and, eventually, a condition called sensorineural hearing loss. More than 460 million people worldwide live with hearing loss that negatively impacts their daily lives, according to the World Health Organization. By 2050, that number is projected to increase to more than 900 million.

Studying mice, researchers at Washington University School of Medicine and the University of Iowa have shown that a drug compound can block damage caused by loud noise, raising the possibility of medication that prevents noise-induced hearing loss. For this preliminary study, a surgical procedure was used to apply the drug directly into the inner ear in a continuous flow. With potential therapies in mind, future research will consider various delivery methods: ear drops, for example, or an injection. The drug compound has not yet been tested in people, but it has been safely administered to small mammals as well as nonhuman primates in other types of neurobiology research, according to the investigators.

“Sensorineural hearing loss is the most common sensory deficit worldwide, and there are no medicinal treatments for preventing it,” says the study’s co-author Mark Rutherford, PhD, assistant professor of otolaryngology at Washington University. “Glutamate receptors are essential for hearing, but overstimulating them can lead to irreversible damage to synapses What we have found is that glutamate receptors are not all the same, allowing us to block some while leaving others unblocked. When we blocked one subclass of glutamate receptor while leaving the other active, we prevented the damage while maintaining hearing function.”

Blocking all of the receptors would, in theory, protect hearing but also cause temporary deafness, similar to the effect of wearing ear plugs. This perhaps would be helpful for long-term hearing preservation but not ideal in situations where people are exposed to dangerous levels of noise but still need to hear what is happening around them.

WHEN WE BLOCKED ONE SUBCLASS OF GLUTAMATE RECEPTOR WHILE LEAVING THE OTHER ACTIVE, WE PREVENTED THE DAMAGE WHILE MAINTAINING HEARING FUNCTION.

MARK RUTHERFORD, PHD

The study’s senior author Steven Green, PhD, of the University of Iowa notes: “Even moderate noise can cause damage to these synapses, and the damage accumulates as we age. With our aging population, the number of people living with disabling hearing loss is increasing rapidly. This is the motivation behind our labs’ collaboration: We are seeking preventive therapies that can protect this vital sensory function in the setting of damaging noise levels while still letting people hear as they normally would.”

Originally published by Washington University School of Medicine at medicine.wustl.edu/news


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