Researchers at Johns Hopkins Medicine have just made a major stride that could restore hearing for people who have irreversible deafness.

In using various genetic tools on mice, the experts found a pair of proteins that precisely control when sound-detecting cells, which are called hair cells, are born in the mammalian inner ear.

“Scientists in our field have long been looking for the molecular signals that trigger the formation of the hair cells that sense and transmit sound,” explained Dr. Angelika Doetzlhofer, associate professor of neuroscience at the Johns Hopkins University School of Medicine. “These hair cells are a major player in hearing loss, and knowing more about how they develop will help us figure out ways to replace hair cells that are damaged.”

For mammals to be able to hear, sound vibrations must travel through the cochlea, which is a hollow, snail shell-looking structure. Inside the cochlea are two types of sound-detecting cells, inner and outer hair cells, which convey sound information to the brain.

It is believed that 90% of genetic hearing loss is caused either by issues with the hair cells or damage to the auditory nerves that connect the hair cells to the brain. When deafness is caused by loud noises or a viral infection, this is due to damage to the hair cells, which can never regenerate. This is why this type of deafness typically ends up being permanent.

It was previously confirmed that the birth of hair cells begins at the outermost part of the spiraled cochlea. This is where precursor cells turn into hair cells along a wave of transformation that stops when it reaches the inner part of the cochlea. Knowing this, Doetzlhofer and her team went looking for molecular cues that were in the right place and at the right time along the cochlear spiral.

They ended up finding a pattern of two proteins, Activin A and Follistatin, that stood out from the others. They noticed that along the cochlea’s spiral path, levels of Activin A increased where precursor cells were turning into hair cells. In contrast, Follistatin had the complete opposite behavior, as its levels were low in the outermost part of the cochlea when precursor cells were first starting to turn into hair cells. The Follistatin levels then got higher at the innermost part of the cochlea’s spiral where precursor cells hadn’t yet started their conversion. Activin A was seen to be moving inward while Follistatin was going outward.

“In nature, we knew that Activin A and follistatin work in opposite ways to regulate cells,” said Doetzlhofer. “And so, it seems, based on our findings like in the ear, the two proteins perform a balancing act on precursor cells to control the orderly formation of hair cells along the cochlear spiral.”

Her team decided to look at these two proteins individually by increasing the levels of Activin A in the cochleas of normal mice. In these mice, the researchers would increase hair cells too early, causing hair cells to appear prematurely all along the cochlear spiral. They then find that in mice who were caused to overproduce follistatin or not produce Activin A at all, hair cells were late to form and appeared disorganized and scattered across multiple rows inside the cochlea.

“The action of Activin A and follistatin is so precisely timed during development that any disturbance can negatively affect the organization of the cochlea,” said Doetzlhofer. “It’s like building a house—if the foundation is not laid correctly, anything built upon it is affected.”

Doetzlhofer concluded by saying that while her research into this is still at an early stage, she thinks it can one day be used to treat deafness caused by damaged hair cells.

“We are interested in how hair cells evolved because it’s an interesting biological question,” she said. “But we also want to use that knowledge to improve or develop new treatment strategies for hearing loss.”