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.

Mass. Eye and Ear Researchers Regenerate Sensory Hair Cells, Restore Hearing to Noise-Damaged Ears

Hearing loss is a significant public health problem affecting almost 50 million people in the United States alone. Sensorineural hearing loss is the most common form and is caused by the loss of sensory hair cells in the cochlea. Hair cell loss results from a variety of factors including noise exposure, aging, toxins, infections, and certain antibiotics and anti-cancer drugs.  Although hearing aids and cochlear implants can ameliorate the symptoms somewhat, there are no known treatments to restore hearing, because auditory hair cells in mammals, unlike those in birds or fish, do not regenerate once lost. Auditory hair cell replacement holds great promise as a treatment that could restore hearing after loss of hair cells.

In the Jan. 10 issue of Neuron, Massachusetts Eye and Ear and Harvard Medical School researchers demonstrate for the first time that hair cells can be regenerated in an adult mammalian ear by using a drug to stimulate resident cells to become new hair cells, resulting in partial recovery of hearing in mouse ears damaged by noise trauma. This finding holds great potential for future therapeutic application that may someday reverse deafness in humans.

“Hair cells are the primary receptor cells for sound and are responsible for the sense of hearing,” explains senior author, Dr. Albert Edge, of Harvard Medical School and Mass. Eye and Ear. “We show that hair cells can be generated in a damaged cochlea and that hair cell replacement leads to an improvement in hearing.”

In the experiment, the researchers applied a drug to the cochlea of deaf mice. The drug had been selected for its ability to generate hair cells when added to stem cells isolated from the ear. It acted by inhibiting an enzyme called gamma-secretase that activates a number of cellular pathways. The drug applied to the cochlea inhibited a signal generated by a protein called Notch on the surface of cells that surround hair cells. These supporting cells turned into new hair cells upon treatment with the drug. Replacing hair cells improved hearing in the mice, and the improved hearing could be traced to the areas in which supporting cells had become new hair cells.

“The missing hair cells had been replaced by new hair cells after the drug treatment, and analysis of their location allowed us to correlate the improvement in hearing to the areas where the hair cells were replaced,” Dr. Edge said.

This is the first demonstration of hair cell regeneration in an adult mammal.  “We’re excited about these results because they are a step forward in the biology of regeneration and prove that mammalian hair cells have the capacity to regenerate,” Dr. Edge said. “With more research, we think that regeneration of hair cells opens the door to potential therapeutic applications in deafness.”

Mechanism of hearing is similar to car battery

University of Iowa biologist Daniel Eberl and his colleagues have shown that one of the mechanisms involved in hearing is similar to the battery in your car.

And if that isn’t interesting enough, the UI scientists advanced their knowledge of human hearing by studying a similar auditory system in fruit flies—and by making use of the fruit fly “love song.”

To see how the mechanism of hearing resembles a battery, you need to know that the auditory system of the fruit fly contains a protein that functions as a sodium/potassium pump, often called the sodium pump for short, and is highly expressed in a specialized support cell called the scolopale cell.

The scolopale cell is important because it wraps around the sensory endings in the fly’s ear and makes a tight extra-cellular cavity or compartment around them called the scolopale space.

“You could think of these compartments as similar to the compartments of a battery that need to be charged up so they can drive electrons through circuits,” says Eberl, whose paper made the cover of the journal Proceedings of the National Academy of Sciences. “In the auditory system, the charge in the scolopale space drives ions, or electrically charged atoms, through membrane channels in the sensory endings that open briefly in response to activation by sounds.

“Our work shows that the sodium pump plays a particularly important role in this cell to help replenish or recharge this compartment with the right ions. The human ear also relies on a compartment called the scala media, which similarly drives ions into the sensory cells of the ear,” he says.

How was the research done? This is where the fruit fly love song comes into play.

Testing whether or not a fruit fly can hear the love song—a sound generated by a vibrating wing—enables Eberl to learn whether electrical recharging is occurring in the fly ear. The fruit fly love song played a role in the research by stimulating the fly to move whenever a sound was emitted and received.

“In these experiments we tested the fly’s hearing by inserting tiny electrodes in the fly’s antenna, then measuring the electrical responses when we play back computer-generated love songs,” he says.

Eberl notes there are many similarities between fruit fly and human mechanisms of hearing. That means his work on the fly model to identify additional new components required for generating the correct ion balance in the ear will help scientists to understand the human process in more detail.

Rhesus monkeys cannot hear beat in music

Beat induction, the ability to pick up regularity – the beat – from a varying rhythm, is not an ability that rhesus monkeys possess. These are the findings of researchers from the University of Amsterdam (UvA) and the National Autonomous University of Mexico (UNAM), which have recently been published in the scientific journal PLOS ONE.

The research conducted by Henkjan Honing, professor of Music Cognition at the UvA, and a team of neurobiologists headed by Hugo Merchant from the UNAM, shows that rhesus monkeys cannot detect the beat in music, although they are able to detect rhythmic groups in music. The results of this research support the view that beat induction is a uniquely human, cognitive skill and contribute to a further understanding of the biology and evolution of human music.

(Photograph by Shane Moore)

HEARBO Robot Has Superhearing

We live in a world of sounds, full of beautiful music, birds chirping, and the voices of our friends. It’s a rich cacophony, with blaring beeps, accented alarms, and knock-knock jokes. The sound of a door opening can alert us to a friend’s arrival, and a door slamming can alert us to an impending argument.

HEARBO (HEAR-ing roBOt) is a robot developed at Honda Research Institute–Japan (HRI-JP), and its job is to understand this world of sound, in a field called Computational Auditory Scene Analysis.

Super-sensory hearing?

The discovery of a previously unidentified hearing organ in the South American bushcrickets’ ear could pave the way for technological advancements in bio-inspired acoustic sensors research, including medical imaging and hearing aid development.

Researchers from the University of Bristol and University of Lincoln discovered the missing piece of the jigsaw in the understanding of the process of energy transformation in the ‘unconventional’ ears of the bushcrickets (or katydids).

Bushcrickets have four tympana (or ear drums) – two on each foreleg; but until now it has been unknown how the various organs connect in order for the insect to hear. As the tympana (a membrane which vibrates in reaction to sound) does not directly connect with the mechanoreceptors (sensory receptors), it was a mystery how sound was transmitted from air to the mechano-sensory cells.

Sponsored by the Human Frontiers Science Program (HFSP), the research was developed in the lab of Professor Daniel Robert, a Royal Society Fellow at the University of Bristol. Dr Fernando Montealegre-Z, who is now at the University of Lincoln’s School of Life Sciences, discovered a newly identified organ while carrying out research into how the bushcricket tubing system in the ear transports sound. The research focussed on the bushcricket Copiphora gorgonensis, a neotropical species from the National Park Gorgona in Colombia, an island in the Pacific. Results suggest that the bushcricket ear operates in a manner analogous to that of mammals. A paper detailing this remarkable new breakthrough is published in the journal, Science.

Medical devices powered by the ear itself

Deep in the inner ear of mammals is a natural battery — a chamber filled with ions that produces an electrical potential to drive neural signals. In today’s issue of the journal Nature Biotechnology, a team of researchers from MIT, the Massachusetts Eye and Ear Infirmary (MEEI) and the Harvard-MIT Division of Health Sciences and Technology (HST) demonstrate for the first time that this battery could power implantable electronic devices without impairing hearing.

The devices could monitor biological activity in the ears of people with hearing or balance impairments, or responses to therapies. Eventually, they might even deliver therapies themselves.

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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)