Auditory brainstem implant: Hearing experts break sound barrier for children born without hearing nerve

February 13, 2015 University of Southern California - Health Sciences Medical researchers are breaking sound barriers for children born without a hearing nerve. Hearing loss manifests in various forms, most of which can be partially restored through hearing aids and cochlear implants. Those devices cannot help a small population of individuals who do not have a cochlear, or hearing, nerve -- these people are unable to perceive sound, no matter how loud, outside of feeling vibration. The ABI is considered revolutionary because it stimulates neurons directly at the human brainstem, bypassing the inner ear entirely. Child's ear (stock image). Medical researchers have successfully implanted an auditory brainstem implant (ABI) device in four children who previously could not hear. A multi-institutional team of hearing and communication experts led by the Keck School of Medicine of the University of Southern California (USC) is breaking sound barriers for children born without a hearing nerve in a clinical trial backed by the National Institutes of Health (NIH). Launched in March 2014, the three-year study has enrolled five of 10 participants and successfully implanted an auditory brainstem implant (ABI) device in four children who previously could not hear. The research team will present preliminary findings at the American Association for the Advancement of Sciences (AAAS) 2015 Annual Meeting in San Jose, California, on Feb. 14. "Initial activation of the ABI is like a newborn entering the world and hearing for the first time, which means these children will need time to learn to interpret what they are sensing through the device as 'sound,'" said audiologist Laurie Eisenberg, Ph.D., a Keck School of Medicine of USC otolaryngology professor and study co-leader. "All of our study participants whose ABIs have been activated are progressing at expected or better rates. We are optimistic that, with intensive training and family support, these children will eventually be able to talk on the phone." Hearing loss manifests in various forms, most of which can be partially restored through hearing aids and cochlear implants. Those devices cannot help a small population of individuals who do not have a cochlear, or hearing, nerve -- these people are unable to perceive sound, no matter how loud, outside of feeling vibration. The ABI is considered revolutionary because it stimulates neurons directly at the human brainstem, bypassing the inner ear entirely. Surgeons outside the United States have been doing ABI surgeries in children for more than 10 years, but there was never a formal safety or feasibility study under regulatory oversight. In the United States, the ABI is approved for use only in patients 12 years or older with neurofibromatosis type II, an inherited disease that causes a non-malignant brain tumor on the hearing nerve, but it has shown limited effectiveness in adults. Scientists believe that the ABI would be more effective in younger children, when their brains are more adaptable. The clinical trial will attempt to prove that the surgery is safe in young children and allow researchers to study how the brain develops over time and how it learns to hear sound and develop speech. "Hearing loss can be devastating to a child's social development, and for some children, the ABI is their last viable chance to hear," said Keck School of Medicine of USC Professor Robert V. Shannon, Ph.D., an investigator for the trial and a leading scientist in the development of ABI technology since 1989. "Several of the young children who had ABIs implanted outside the United States have sought help at the USC-CHLA Center for Childhood Communication and we know that they now have the potential to understand speech. This really shows how powerful and flexible the brain is. By studying how the brain and the hearing system work together through this device, our team will set the gold standard for use of this technology." Story Source: The above story is based on materials provided by University of Southern California - Health Sciences. Note: Materials may be edited for content and length.

Scientists restore hearing in noise-deafened mice, pointing way to new therapies

 

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.

In a new paper in the online journal eLife, the team from the University of Michigan Medical School's Kresge Hearing Research Institute and Harvard University report 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.

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 that 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," says Gabriel Corfas, Ph.D., who led the team and directs the U-M institute. "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. It's very exciting."

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, Ph.D., Maria E. Gómez-Casati, Ph.D., and others in his former institution, Harvard. Some of the authors now work with Corfas in his new U-M lab. 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.

Anyone who has experienced problems making out the voice of the person next to them in a crowded room has felt the effects of reduced ribbon synapses. So has anyone who has experienced temporary reduction in hearing after going to a loud concert. 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 that 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 that 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 and Gómez-Casati, who now works in Argentina, the research was performed by Angelica R. Gigliello, and M. Charles Liberman, Ph.D. director of the Eaton-Peabody Laboratories of the Massachusetts Eye and Ear Infirmary. 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.

Smokers, passive smokers more likely to suffer hearing loss, study shows

 

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Giving up or reducing smoking and avoiding passive exposure to tobacco smoke may reduce your risk of hearing loss, new research shows.

Smokers and passive smokers more likely to suffer hearing loss, study shows

Current smokers have a 15.1% higher odds of hearing loss than non-smokers The University of Manchester study, funded by Action on Hearing Loss, Medical Research Council and the National Institute for Health Research, found.

Passive smoking also increased the likelihood of hearing loss by 28%.

But ex-smokers had a slightly reduced risk of going deaf -- which may be because once they quit they adopt a more healthy life style overall.

The study is published in the Journal of the Association for Research in Otolaryngology today.

Researchers looked at 164,770 UK adults aged 40 to 69 years of age who took hearing tests between 2007 and 2010 when they joined UK Biobank, a national project to improve health.

Dr Piers Dawes, from the Centre for Human Communication and Deafness at The University of Manchester who led the research, said: "Given around 20% of the UK population smoke and up to 60% in some countries, smoking may represent a significant cause of hearing loss worldwide.

"We found the more packets you smoke per week and the longer you smoke, the greater the risk you will damage your hearing."

The link between smoking and hearing loss is still unclear but many smokers also often had heart disease.

Dr Dawes added: "We are not sure if toxins in tobacco smoke affect hearing directly, or whether smoking-related cardiovascular disease causes microvascular changes that impact on hearing, or both."

The increased risk among passive smokers -- higher than that for smokers -- could be because smokers were compared to both complete non-smokers and passive non-smokers but passive smokers were only compared to non-smokers.

This means the association with smoking and hearing loss maybe under estimated, the researchers say.

Dr Ralph Holme, Head of Biomedical Research at Action on Hearing Loss, said "Hearing loss affects 10 million people in the UK and with an aging population is set to become a major public health issue.

"Hearing loss is often viewed as an inevitable consequence of aging, but as the research published today shows, this may not always be the case. Giving up smoking and protecting your ears from loud noise are two practical steps people can take today to prevent hearing loss later in life."

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Story Source:

The above story is based on materials provided by Manchester University. Note: Materials may be edited for content and length.

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Journal Reference:

1. Piers Dawes, Karen J. Cruickshanks, David R. Moore, Mark Edmondson-Jones, Abby McCormack, Heather Fortnum, Kevin J. Munro. Cigarette Smoking, Passive Smoking, Alcohol Consumption, and Hearing Loss. Journal of the Association for Research in Otolaryngology, 2014; DOI: 10.1007/s10162-014-0461-0