Discovering the Missing “LINC” to Deafness

Because half of all instances of hearing loss are linked to genetic mutations, advanced gene research is an invaluable tool for uncovering causes of deafness — and one of the biggest hopes for the development of new therapies. Now Prof. Karen Avraham of the Sackler Faculty of Medicine at Tel Aviv University has discovered a significant mutation in a LINC family protein — part of the cells of the inner ear — that could lead to new treatments for hearing disorders.

Her team of researchers, including Dr. Henning Horn and Profs. Colin Stewart and Brian Burke of the Institute of Medical Biology at A*STAR in Singapore, discovered that the mutation causes chaos in a cell’s anatomy. The cell nucleus, which contains our entire DNA, moves to the top of the cell rather than being anchored to the bottom, its normal place. Though this has little impact on the functioning of most of the body’s cells, it’s devastating for the cells responsible for hearing, explains Prof. Avraham. “The position of the nucleus is important for receiving the electrical signals that determine proper hearing,” she explains. “Without the ability to receive these signals correctly, the entire cascade of hearing fails.”

This discovery, recently reported in the Journal of Clinical Investigation, may be a starting point for the development of new therapies. In the meantime, the research could lead towards work on a drug that is able to mimic the mutated protein’s anchoring function, and restore hearing in some cases, she suggests.

New implant replaces impaired middle ear

Functionally deaf patients can gain normal hearing with a new implant that replaces the middle ear. The unique invention from the Chalmers University of Technology has been approved for a clinical study. The first operation was performed on a patient in December 2012.

With the new hearing implant, developed at Chalmers in collaboration with Sahlgrenska University Hospital in Gothenburg, the patient has an operation to insert an implant slightly less than six centimetres long just behind the ear, under the skin and attached to the skull bone itself. The new technique uses the skull bone to transmit sound vibrations to the inner ear, so-called bone conduction.

“You hear 50 percent of your own voice through bone conduction, so you perceive this sound as quite natural”, says Professor Bo Håkansson, of the Department of Signals and Systems, Chalmers.

The new implant, BCI (Bone Conduction Implant), was developed by Bo Håkansson and his team of researchers. Unlike the type of bone-conduction device used today, the new hearing implant does not need to be anchored in the skull bone using a titanium screw through the skin. The patient has no need to fear losing the screw and there is no risk of skin infections arising around the fixing.

The first operation was performed on 5 December 2012 by Måns Eeg-Olofsson, Senior Physician at Sahlgrenska University Hospital, Gothenburg, and went entirely according to plan.

“Once the implant was in place, we tested its function and everything seems to be working as intended so far. Now, the wound needs to heal for six weeks before we can turn the hearing sound processor on”, says Måns Eeg-Olofsson, who has been in charge of the medical aspects of the project for the past two years.

The technique has been designed to treat mechanical hearing loss in individuals who have been affected by chronic inflammation of the outer or middle ear, or bone disease, or who have congenital malformations of the outer ear, auditory canal or middle ear. Such people often have major problems with their hearing. Normal hearing aids, which compensate for neurological problems in the inner ear, rarely work for them. On the other hand, bone-anchored devices often provide a dramatic improvement.

In addition, the new device may also help people with impaired inner ear. “Patients can probably have a neural impairment of down to 30-40 dB even in the cochlea. We are going to try to establish how much of an impairment can be tolerated through this clinical study”, says Bo Håkansson.

If the technique works, patients have even more to gain. Earlier tests indicate that the volume may be around 5 decibels higher and the quality of sound at high frequencies will be better with BCI than with previous bone-anchored techniques. Now it’s soon time to activate the first patient’s implant, and adapt it to the patient’s hearing and wishes. Then hearing tests and checks will be performed roughly every three months until a year after the operation.

“At that point, we will end the process with a final X-ray examination and final hearing tests. If we get good early indications we will continue operating other patients during this spring already”, says Måns Eeg-Olofsson.

The researchers anticipate being able to present the first clinical results in early 2013. But when will the bone-conduction implant be ready for regular patients?

“According to our plans, it could happen within a year or two. For the new technique to quickly achieve widespread use, major investments are needed right now, at the development stage”, says Bo Håkansson.

Diary of becoming an NHS-funded cyborg

From the day I was born, my brain developed according to the stimuli it received. My senses of vision, touch, taste, smell were all slightly heightened in compensation for the lack of input from my ears, helping me to create a world I could understand.

My mother worked full time with me, playing a set of activities she called “the game”. I was a child, and didn’t understand the real reason for playing the game — but it taught me to read, write, lipread, and speak, if not to hear in the traditional sense of the word. What I do hear is filtered through digital hearing aids that amplify what little sound I can hear.

A month ago, for the first time, I made the change from external technology to internal technology. I became a full time cyborg, free of charge on the NHS.

They cut away a flap of skin behind my left ear, drilled a tiny hole into my skull between the two main nerves of the face that control taste and the face, and inserted an electrode into my cochlear, connected to a small magnet and circuit board under the skin.

They’re going to switch me on in a few days — and if it’s all working as it should, my auditory cortex will be bombarded by a range of electronic noises. Over time, I may come to understand these sounds as consonants, music, even the spoken word.

This is what it will sound like, apparently.

Even if I can make sense of those sounds, it won’t be “hearing” in the normal sense of the word. My ears have had the same level of input for the last 30 years of my life — and now I’ve physically rewired one of them to receive a completely different signal.

In all the recent blue sky thinking on Wired.co.uk and elsewhere about the future of the human race — coprocessors for the brain, enhanced spectrum bionic eyes, artificial legs, even the possibility of interfacing with computers directly — people forget one thing. What it feels like, what it’s like to live with it every day, whether it makes you feel more, or less, yourself.

I’m also wary of augmentation and body enhancement becoming the norm. We have a fluid definition of what a disability is, and what isn’t. If certain people with access to this technology start engineering themselves to have greater physical or mental abilities, then where does that leave ordinary people? Differently abled? Or Disabled? Or in fact more abled? In giving up perfectly usable eyes, the end result of millions of years of evolution, to install digital eyes that can project images onto the retina, are we really putting ourselves at an advantage?

If I’d been born into a deaf family, all of us signing, my brain developing to become fluent in sign language and developing a deaf identity so strong and complete that I saw deafness as “normal” and hearing as “abnormal” — I wouldn’t have had this implant.

The cochlear implant, in crossing the line from external wearable technology to permanent fixture, becomes a technology that is potentially in conflict with human values, rather than a testament to them. Many deaf people see the cochlear implant as a symbol of medical intervention, to oppress and ultimately eradicate the deaf community and deaf culture, by fixing them one implant at a time — this includes implanting children at an early age so that they’ll be able to acquire spoken language rather than sign.

Scripps Research Institute Scientists Identify Molecules in the Ear that Convert Sound into Brain Signals

For scientists who study the genetics of hearing and deafness, finding the exact genetic machinery in the inner ear that responds to sound waves and converts them into electrical impulses, the language of the brain, has been something of a holy grail.

Now this quest has come to fruition. Scientists at The Scripps Research Institute (TSRI) in La Jolla, CA, have identified a critical component of this ear-to-brain conversion—a protein called TMHS. This protein is a component of the so-called mechanotransduction channels in the ear, which convert the signals from mechanical sound waves into electrical impulses transmitted to the nervous system.

“Scientists have been trying for decades to identify the proteins that form mechanotransduction channels,” said Ulrich Mueller, PhD, a professor in the Department of Cell Biology and director of the Dorris Neuroscience Center at TSRI who led the new study, described in the December 7, 2012 issue of the journal Cell.

Not only have the scientists finally found a key protein in this process, but the work also suggests a promising new approach toward gene therapy. In the laboratory, the scientists were able to place functional TMHS into the sensory cells for sound perception of newborn deaf mice, restoring their function. “In some forms of human deafness, there may be a way to stick these genes back in and fix the cells after birth,” said Mueller.

TMHS appears to be the direct link between the spring-like mechanism in the inner ear that responds to sound and the machinery that shoots electrical signals to the brain. When the protein is missing in mice, these signals are not sent to their brains and they cannot perceive sound.

Specific genetic forms of this protein have previously been found in people with common inherited forms of deafness, and this discovery would seem to be the first explanation for how these genetic variations account for hearing loss.

Brain waves make waves

Naturally, our brain activity waxes and wanes. When listening, this oscillation synchronizes to the sounds we are hearing. Researchers at the Max Planck Institute for Human Cognitive and Brain Sciences have found that this influences the way we listen. Hearing abilities also oscillate and depend on the exact timing of one’s brain rhythms. This discovery that sound, brain, and behaviour are so intimately coupled will help us to learn more about listening abilities in hearing loss.

Gene That Causes a Form of Deafness Discovered

Researchers at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center have found a new genetic mutation responsible for deafness and hearing loss associated with Usher syndrome type 1.

These findings, published in the Sept. 30 advance online edition of the journal Nature Genetics, could help researchers develop new therapeutic targets for those at risk for this syndrome.

Partners in the study included the National Institute on Deafness and other Communication Disorders (NIDCD), Baylor College of Medicine and the University of Kentucky.

Usher syndrome is a genetic defect that causes deafness, night-blindness and a loss of peripheral vision through the progressive degeneration of the retina.

(Image credit: GETTY)

Giving a voice to the voiceless has been a cause that many have championed throughout history, but it’s safe to say that none of those efforts involved packing a bunch of sensors into a glove. A team of Ukrainian students has done just that in order to translate sign language into vocalized speech via a smartphone.

The inspiration for the gloves came from observing fellow college students who were deaf have difficulty communicating with other students, which results in them being excluded from activities. Initially, the team looked at commercially available gloves that could be modified to interpret a range of signs, but in the end, they opted to develop their own.

In their glove, a total of 15 flex sensors in the fingers measure the degree of bending while a compass, accelerometer, and gyroscope determine the motion of the glove through space. The sensor data are processed by a microcontroller on the glove then sent via Bluetooth to a mobile device, which translates the positions of the hand and fingers into text when the pattern is recognized. Using Microsoft APIs for Speech and Bing, the text is spoken by the phone running Windows Phone 7. The glove can also plug into a PC for data syncing and charging of its battery.

Stem Cells Turn Hearing Back On

Scientists have enabled deaf gerbils to hear again—with the help of transplanted cells that develop into nerves that can transmit auditory information from the ears to the brain. The advance, reported in Nature, could be the basis for a therapy to treat various kinds of hearing loss.

In humans, deafness is most often caused by damage to inner ear hair cells—so named because they sport hairlike cilia that bend when they encounter vibrations from sound waves—or by damage to the neurons that transmit that information to the brain. When the hair cells are damaged, those associated spiral ganglion neurons often begin to degenerate from lack of use. Implants can work in place of the hair cells, but if the sensory neurons are damaged, hearing is still limited.

"Obviously the ultimate aim is to replace both cell types," says Marcelo Rivolta of the University of Sheffield in the United Kingdom, who led the new work. "But we already have cochlear implants to replace hair cells, so we decided the first priority was to start by targeting the neurons."

In the past, scientists have tried to isolate so-called auditory stem cells from embryoid bodie—aggregates of stem cells that have begun to differentiate into different types. But such stem cells can only divide about 25 times, making it impossible to produce them in the quantity needed for a neuron transplant.

Rivolta and his colleagues knew that during embryonic development, a handful of proteins, including fibroblast growth factor (FGF) 3 and 10, are required for ears to form. So they exposed human embryonic stem cells to FGF3 and FGF10. Multiple types of cells formed, including precursor inner-ear hair cells, but they were also able to identify and isolate the cells beginning to differentiate into the desired spiral ganglion neurons. Then, they implanted the neuron precursor cells into the ears of gerbils with damaged ear neurons and followed the animals for 10 weeks. The function of the neurons was restored.

"We’ve only followed the animals for a very limited time," Rivolta says. "We want to follow them long-term now"—both to assess the possibility of increased cancer risk and to observe the long-term function of the new neurons, he adds.

"It’s very exciting," says neuroscientist Mark Maconochie of Sussex University in the United Kingdom, who was not involved in the new work. "In the past, there has been work where someone makes a single hair cell or something that looks like one neuron [from stem cells], and even that gets the field excited. This is a real step change."

The question now, he says, is whether the procedure can be fine-tuned to allow more efficient production of the relay neurons—currently, fewer than 20% of the stem cells treated develop into those ear neurons. By combining growth factors other than FGF3 and FGF10 with the stem cell mix, researchers could harvest even more ear progenitor cells, he hypothesizes.

"The next big challenge will be to do something as effective as this for the hair cells," Maconochie adds.

Earphones ‘potentially as dangerous as noise from jet engines,’ according to new University of Leicester study: New research identifies for the first time how high volumes of sound damage nerve cell coating leading to temporary deafness.

University of Leicester researcher Dr Martine Hamann of the Department of Cell Physiology and Pharmacology, who led the study, said:

"The research allows us to understand the pathway from exposure to loud noises to hearing loss. Dissecting the cellular mechanisms underlying this condition is likely to bring a very significant healthcare benefit to a wide population. The work will help prevention as well as progression into finding appropriate cures for hearing loss.”