Say what?
Scientists have restored the hearing of mice partly deafened by noise, using advanced tools to boost the production of a key protein in their ears.
By demonstrating the importance of the protein, called NT3, in maintaining communication between the ears and brain, these new findings pave the way for research in humans that could improve treatment of hearing loss caused by noise exposure and normal aging.
That’s music to the ears of anyone who has experienced problems making out the voice of the person next to them in a crowded room, or struggled with temporary reduction in hearing after a loud concert.
“We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people, ” says Gabriel Corfas, PhD, who led the research team. “It’s very exciting.”
Best supporting actors
Corfas directs the University of Michigan Medical School’s Kresge Hearing Research Institute. His team collaborated with scientists from Harvard University; their new paper in the online journal eLife reports the results of their work to understand NT3’s role in the inner ear, and the impact of increased NT3 production on hearing after a noise exposure.
This microscopic view of cells deep within the ear of a newborn mouse show in red and blue the supporting cells that surround the hair cells (green) that send sound signals to the brain. New research shows that the supporting cells can regenerate if damaged in the first days of life, allowing hearing to develop normally. This gives new clues for potential ways to restore hearing. (Image credit: Guoqiang Wan.)
Their work also illustrates the key role of cells that have traditionally been seen as the “supporting actors” of the ear-brain connection. Called supporting cells, they form a physical base for the hearing system’s “stars”: the hair cells in the ear that interact directly with the nerves that carry sound signals to the brain. This new research identifies the critical role of these supporting cells along with the NT3 molecules they produce.
NT3 is crucial to the body’s ability to form and maintain connections between hair cells and nerve cells, the researchers demonstrate. This special type of connection, called a ribbon synapse, allows extra-rapid communication of signals that travel back and forth across tiny gaps between the two types of cells.
“It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it’s due to noise or normal aging,” Corfas says.
A specific target to pursue
Using a special genetic technique, the researchers made it possible for some mice to produce additional NT3 in cells of specific areas of the inner ear after they were exposed to noise loud enough to reduce hearing. Mice with extra NT3 regained their ability to hear much better than the control mice.
Now, says Corfas, his team will explore the role of NT3 in human ears, and seek drugs that might boost NT3 action or production. While the use of such drugs in humans could be several years away, the new discovery gives them a specific target to pursue.Corfas, a professor and associate chair in the U-M Department of Otolaryngology, worked on the research with first author Guoqiang Wan, PhD, Maria E. Gómez-Casati, PhD, and others in his former institution, Harvard, as well as M. Charles Liberman, PhD, director of the Eaton-Peabody Laboratories of the Massachusetts Eye and Ear Infirmary. Some of the authors now work with Corfas in his new U-M lab.
Together, they set out to find out how ribbon synapses – which are found only in the ear and eye – form, and what molecules are important to their formation and maintenance. The damage caused by noise – over a lifetime or just one evening – reduces the ability of hair cells to talk to the brain via ribbon synapse connections with nerve cells.
Targeted genetics made discovery possible
After determining that inner ear supporting cells supply NT3, the team turned to a technique called conditional gene recombination to see what would happen if they boosted NT3 production by the supporting cells. The approach allows scientists to activate genes in specific cells, by giving a dose of a drug that triggers the cell to “read” extra copies of a gene that had been inserted into them. For this research, the scientists activated the extra NT3 genes only into the inner ear’s supporting cells.
The genes didn’t turn on until the scientists wanted them to – either before or after they exposed the mice to loud noises. The scientists turned on the NT3 genes by giving a dose of the drug tamoxifen, which triggered the supporting cells to make more of the protein. Before and after this step, they tested the mice’s hearing using an approach called auditory brainstem response or ABR – the same test used on humans.The result: The mice with extra NT3 regained their hearing over a period of two weeks, and were able to hear much better than mice without the extra NT3 production. The scientists also did the same with another nerve cell growth factor, or neurotrophin, called BDNF, but did not see the same effect on hearing.
Next steps
Now that NT3’s role in making and maintaining ribbon synapses has become clear, Corfas says the next challenge is to study it in human ears, and to look for drugs that can work like NT3 does. Corfas has some drug candidates in mind, and hopes to partner with industry to look for others.
Boosting NT3 production through gene therapy in humans could also be an option, he says, but a drug-based approach would be simpler and could be administered as long as it takes to restore hearing.Corfas notes the mice in the study were not completely deafened, so it’s not yet known if boosting NT3 activity could restore hearing that has been entirely lost. He also notes the research may have implications for other diseases in which nerve cell connections are lost – called neurodegenerative diseases.
“This brings supporting cells into the spotlight, and starts to show how much they contribute to plasticity, development, and maintenance of neural connections,” he says.
In addition to Corfas, Wan, Liberman and Gómez-Casati, who now works in Argentina, the research team included Angelica R. Gigliello. The research was supported by the National Institute on Deafness and Other Communication Disorders (DC004820, DC005209) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655), both part of the National Institutes of Health, and by the Hearing Health Foundation.
Top image: Microscope image of tissue from deep inside a normal mouse ear shows how ribbon synapses (red) form the connections between the hair cells of the inner ear (blue) and the tips of nerve cells (green) that connect to the brain. (Credit: Eaton-Peabody Laboratory, Mass. Eye and Ear.)
This story appears courtesy of the University of Michigan Health System.
Margaret Bennett - 1958, 1975
Have been interested in your research to improve hearing loss for a few years. (There was a story in one of the “local’ newspapers. (I live in Ann Arbor.)
Have been too busy this past year with some other health problems to contact you–I still have the story.
My hearing loss comes from either genetics, or a bout with the ‘hard measles’ when I was 2 1/2, that left me deaf for 3 months. Lucky me–my hearing came back.
But I have been bothered for the past 25 years with hearing loss. Wear 2 aids, which need to be replaced pretty soon.
Please keep up the fine work.
Thanks,
–Margaret R Bennett
Ann Arbor, MI
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Sreek Cherukuri - 1994, 1998
I am a board certified ear, nose, and throat surgeon and find this article very interesting. On a related note, I founded a company called MDHEARINGAID aid to help the millions of Americans that have hearing loss but can’t afford the high prices of today’s custom hearing aids.
MDHearingAid manufactures low cost FDA-registered hearing aids starting under $200.
SREEK Cherukuri MD
Chicago, IL
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melissa hotz
Doctor,
I am curious if your aides will help if complete hearing loss has occured? I am 39 years old, and lost the hearing in my right ear suddenly 3 years ago. It has been replaced with a constant ringing. I have been to many doctors, had many test, and have been told there is nothing that can be done
I keep praying something new will be developed to restore my hearing.
Thank You!
Mrs. Hotz
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David Andrews - 1953 & 1956
I am 83 years old and work at a health club where I have substantial member interaction. My hearing aids (from the VA) are marvelous but are somewhat line-of-sight – don’t work well for sounds coming from behind. I think my hearing loss started when I was 19 and worked in an auto factory in Detroit where they tested stamping extremely thick steel plate – on the days when they did that it would take 4 to 5 hours after leaving work before I could hear anything. Will there be volunteer testing for this restoration procedure? Would be very interested if there is! Thanks.
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Former Soldier - 1988
My time with the Army has left me with hearing loss. Mufflers are required on cars, but are discouraged on firearms (or outright illegal in many states). Small, inexpensive mufflers could reduce gunshot noise enough to reduce hearing loss while still leaving them “loud” enough to leave an audible signature.
It’s time to repeal the ridiculous laws against firearm mufflers.
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Ann Dickey - 1947 1967 1979
If you start tests on human subjects while I am still on the planet, I’d like to be considered.
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Peter Logan
My hearing loss began in 1985, concurrent with sudden tinnitus in my left ear. As the hearing diminished, CAT scans, MRIs and four specialists diagnosed the problem as genetic hearing loss, similar to what my father and his brother experienced. The cilia in the cochlea of the left ear were deteriorating. An intense steroid treatment attempted to “kick” the cochlea back into action, but just kicked it over the edge. (The physician was very clear about the potential of complete hearing loss in the left ear by trying this treatment. I agreed to the risk.)
The research on NT3 is fascinating, and I wish the doctors and researchers further success. And if they are looking for volunteers for human trials, count me in.
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Katherine Eagan - 1972, 2005
I lost my hearing at the age of 34 from barotrauma when the plane lost cabin pressure. I am now 60. Mine is a bilateral sensory neural loss and I only have 30% speech recognition when aided. I would be volunteer to be a guinea pig in a heart beat if I there was a chance my hearing could be restored. I am deaf without the aids.
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Shirley Conley - 1970
This is such exciting news! Thank you so much . I lost my hearing in my right ear in 2009, due to a loud grinding noise in an enclosed garage, I was working in. I have fairly good hearing in my left. But still can’t tell exactly what direction the sound is coming from. In my right ear, If the sound is loud enough I can get a muffled sound, as if a broken speaker, nothing I can understand. I would welcome the opportunity to be a part of this study. Thank you so much, Shirley Conley
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Brianna Colliau
I found this article very interesting! I am 26 and I have severe high pitched hearing loss in my right ear that started a little over a year ago with an unknown cause. I would hope at one point there would be a possibility to enjoy all of my hearing again, and this has made me hopeful that there might be a chance in the future!
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Cheryl Buchanan - 1972 and 1981
would be a very willing volunteer. Have a hereditary hearing loss..nerve deafness. No hearing in left ear and very little in right one. It is a progressive hearing loss.
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Jeffrey Ford - 1969
I’ve been wearing hearing aids since 1977 after finding out about my hearing loss in 1973. It is high frequency loss with tinnitus. No know cause was ever diagnosed. I am able to function with my hearing aids, but it becomes more difficult every year. I would be happy to participate in any study that happens.
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Melissa Hotz
I am 39 years old and lost the hearing in my right ear 3 years ago suddenly, and unknown cause. I would love to volunteer for a human study if it becomes available. I
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