Tag Archives: deafness

Gene therapy restores hearing in deaf mice, paving the way for human treatment

In Mark 7:31-34, everyone’s favorite Galilean cured a deaf man so that he could hear again. Not ones to be one up-ed so easily, researchers injected genetically modified viruses – a procedure known as virotherapy – to replace faulty genes in mice with genetic deafness to help restore their hearing, and the results are promising.

By the look on its furry little face, it’s probably Skrillex.
Image via: head-fi.org

We wrote about how gene therapy was used to restore hearing in guinea pigs and how drugs were used to promote regeneration in mice’s ears. But those trials aimed to treat the effects of noise trauma. Now, researchers tried to restore hearing to mice that suffered from genetic hearing loss.

Some of them could sense and respond to noises after receiving working copies of their faulty genes, researchers report on July 8 in Science Translational Medicine. Because the mice’s mutated genes closely correspond to those responsible for some hereditary human deafness, the scientists hope the results will inform future human therapies.

Inner ear hair cells, responsible for “catching” sound waves, viewed under an electron microscope.
Image via: asbmb.org

“I would call this a really exciting big step,” says otolaryngologist Lawrence Lustig of Columbia University Medical Center.

The ear uses specialized sound-sensing cells, named hair cells that convert movement in their environment -i.e. noises- into information the brain can process. Hair cells need specific proteins to work properly, and alterations in the genetic blueprints for these proteins can cause deafness.

To combat the effects of two such mutations, the scientists injected viruses containing healthy, functioning versions of the genes into the ears of deaf baby mice. The virus infected some hair cells, giving them working genes.

A mutation causes sound-sensing cells (bright green) to die off quickly in deaf mice, but gene therapy can rescue these cells (right) in mice given a virus that delivers a working gene. Two inner ear locations are shown.
Image via: sciencenews.org

The method was used on mice showing two different types of deafness-causing mutations. For one of them, mice showed neural activity indicative of hearing, and even jumped (adorably so, probably; the study sadly does not mention) when exposed to loud noises. Treated mice with the other mutation didn’t respond to noises, but the gene therapy helped their hair cells — which normally die off quickly due to the mutation — survive. All of the untreated mice, in the control group, remained deaf.

It is however a partial fix. The mice that responded to the treatment had most of their inner hair cells, that allow basic hearing, use the new genes. But few outer hair cells, which amplify noises, accepted the viral delivery. It’s hard to get outer hair cells to respond to gene therapy, Lustig says. Still, inner hair cells control most sound transmission, he added.

The scientists hope to eventually identify the right virus and genetic instructions to treat all hair cells and get complete recovery of hearing, says study coauthor Jeffrey Holt, a neuroscientist at Boston Children’s Hospital. The team’s immediate goals are to improve the viral infection rate and test if the treatment can last for long time periods, Holt says. He also mentioned that the viruses used to deliver the genes are safe and already used in human gene therapies.

Gene therapies must work as well as existing cochlear implant technologies to become a good treatment option, Lustig adds. But a functioning inner ear would ultimately do a far better job than any cochlear implant could.

“Ultimately, we’ll get there.”


This device could let deaf people “hear” via their tongues

Out of all the solutions which could help deaf people here, this is definitely one of the most creative things I’ve seen. Researchers from the US have developed an electric mouthpiece that can transmit sounds to people – through their tongues.

The device is also cheap, widely effective, and very little invasive. The device uses a Bluetooth-enabled earpiece to pick up sounds, then converts them into electrical signals, and then convert them into vibrations which the users can hear by pushing their tongues up.

The mechanism is fairly similar to how current cochlear implants work, except you don’t need any surgery to implement it. The new mouthpiece also doesn’t require a patient’s auditory nerve to be functional, so it can be used by virtually all people suffering from deafness or similar related issues.

“It’s much simpler than undergoing surgery and we think it will be a lot less expensive than cochlear implants,” said John Williams, a mechanical engineer from Colorado State University, who co-led the project, in a press release. Cochlear implants are very effective and have transformed many lives, but not everyone is a candidate. We think our device will be just as effective but will work for many more people and cost less.”

The only downside is that this technology requires some training from the user, but that shouldn’t be much of a problem. They chose the tongue because the tongue is a very powerful muscle with thousands of nerves which can be used.

For this to work, people would have to be taught something like a whole new language, but it’s not especially difficult, and he explains how people could be taught this new language in the video below. This means that people can be taught to translate vibrations on their tongue into words – effectively allowing them to hear. Unfortunately, it will take a long time before this technology can be used by the public, but the prototypes are already ready.

So, what do you think about this? Is it innovative and can help numerous people, or is it just too quirky to work?

Images via Science Alert.


Songbirds inspire next generation hearing aid, faithful to the human ear

Hearing loss can be devastating: you lose friends, become ever trapped inside your head and alienated from society. Yet, only one in five Americans choose to use a hearing aid. Some ignore their problem, others can’t afford treatment or installing a hearing aid, but really a lot of people choose not to wear a hearing aid because it can be just too unbearable. This might change for the better in the future, though. For instance, scientists at University of California are developing a next-generation hearing aid inspired by songbirds that emulates the human ear as realistically as possible.

Was that a chip or a chirp?


Image credits: Virginia Green (http://virginiagreene.tumblr.com/)

All hearing aids have the same basic parts: a microphone, the tonehook or earhook, the volume control, the on/off switch and the battery door. The microphone picks up sounds and sends them to an amplifier that makes them louder. The hearing aid will make some pitches of sound louder than others, depending on the shape of the hearing loss. But Hearing aids aren’t effective for everyone. Hair cells in the inner ear must pick up the vibrations that the hearing aid sends and convert those vibrations into nerve signals. So, you need to have at least some hair cells in the inner ear for it to work. Moreover, most devices aren’t that well tuned, so must of your environment gets equally amplified – this can drive anyone crazy.

“In a crowded place, it can be very difficult to follow a conversation even if you don’t have hearing deficits,” says UC Berkeley neuroscientist Frederic Theunissen. “That situation can be terrible for a person wearing a hearing aid, which amplifies everything.”

Image your sitting in a crowded bar, at a table with your friends. Despite the racket and rattle around, you have no problem having a conversation with your friends because the human brain and ear work together beautifully to hone in on a particular signal – the rest is just background noise that isn’t processed consciously. With a hearing aid, this sort of differentiation is very difficult. So, the ultimate goal is to build a hearing aid that transmits signals and processes audio much in the way the brain would.

[ALSO SEE] Hearing restored in mice following hair cell regeneration therapy

Humans aren’t the only ones capable of differentiating between audio signals. Among other animals that are very apt at this is the songbird. For the past two years, Theunissen and colleagues have analyzed the brain imagery of songbirds to understand how these can distinguish between the chirp of a mate from dozens if not hundreds of strangers. The team eventually identified the exact neurons involved in this process which tune into a signal and remain tuned indifferent of how noisy the environment is. Theunissen calls this an “auditory spotlight”. Imagine you’re looking for your car keys on the dinner table. You have this particular shape, texture and colour that you’re searching for among plates, breadcrumbs and cats. In a similar way to the eye, the ear searchers and finds particular pitches and frequencies – say the voice of your friends at the bar.

“Our brain does all this work, suppressing echoes and background noise, conducting auditory scene analysis,” Theunissen says.

The “auditory spotlight” process has been reproduced in an algorithm, and now the UC team is working with a company to test whether the company can improve performance if installed on conventional hearing aids. This next generation of hearing aids will detect the features of the signal and separate it from any background noise. Unlike a traditional hearing aid, it will have a variable gain so that signal sounds get a boost without distortion, while background sounds are attenuated without being completely muffled out.

“This hearing aid should not eliminate all of the noise or distort the signal,” Theunissen says. “That wouldn’t sound real, and the real sound is the most pleasant and the one that we want to hear.”

sensory hair cells

Hearing restored in mice after hair cells were regenerated through drug

Hearing loss is a grave healthcare problem around the world, with 50 million cases in the US alone. The most common type is sensorineural hearing loss caused by the degradation and loss of sensory hair cells in the cochlea (the auditory part of the inner ear). While implants and various other hearing aids can improve hearing a tad, significant improvement can not be achieved since these sensory hair cells do not regenerate for mammals. In a remarkable breakthrough moment, scientists at Massachusetts Eye and Ear and Harvard Medical School developed a drug that can regenerate sensory hair cells in mouse ears damaged by noise trauma.

Fluid movement in the inner ear (cochlea), like sound waves propagating, causes changes in tiny structures called hair cells. As these hair cells move, electrical signals from the cochlea are sent up the auditory nerve to the brain, which is then converted into information we can commonly refer to as sound. Hair cell loss comes from noise exposure, aging, toxins, infections, and certain antibiotics and anti-cancer drug.

“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.”

Fighting deafness

sensory hair cellsBirds or fish can regenerate their damaged or lost hair cells, however mammals can not. The researchers tested their novel drug by applying it to the cochlea of deaf mice, which had their hearing impaired from sound trauma. The drug works 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.

After the drug was administered significant hearing improvements were observed in mice, and further observations showed that improved hearing could be traced to the areas in which supporting cells had become new hair cells. The breakthrough is the latest in a slew of research that demonstrate hearing improvements in mammals – previously, we reported how improvements in mice hearing were made after scientists injected the cochlea with nasal stem cells, hair cell regeneration in gerbils again through stem cells and gene therapy that rendered similar results in guinea pigs.

“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.

“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.”

Findings were documented in the journal Science.

source: Massachusetts Eye and Ear 

Human stem cell-derived otic neurons repopulating the cochlea of deaf gerbils. Human cells are labelled green, and the red is a marker of neuronal differentiation. Therefore yellow cells are neurons of human origin. (c) University of Sheffield

Hearing restored in gerbils by stem cell treatment – might work for the human ear, too

In an exceptional feat of medical and technical ingenuity, scientists have been able to restore partial hearing to deaf gerbils by implanting modified human embryonic stem cells in their ears. The success rate is pleasing, and offers solid ground on which human trials with a similar treatment might commence.

Human stem cell-derived otic neurons repopulating the cochlea of deaf gerbils. Human cells are labelled green, and the red is a marker of neuronal differentiation. Therefore yellow cells are neurons of human origin. (c) University of Sheffield

Human stem cell-derived otic neurons repopulating the cochlea of deaf gerbils. Human cells are labelled green, and the red is a marker of neuronal differentiation. Therefore yellow cells are neurons of human origin. (c) University of Sheffield

There are many causes which might lead to hearing loss. The leading cause by far is related to damage to a special cell located inside the ear, equipped with hairs that sense vibrations and transmit them back to the brain through the neural connection to be decoded as sound. Another cause, however, experienced by 10% of the approximate 275 million people worldwide suffering from some form of hearing loss, is a condition called auditory neuropathy – the impairment of auditory neurons.

Targeting this specific deafness factor, the researchers at University of Sheffield UK implanted 18 gerbils, which had their auditory nerves rendered nonfunctional in the lab, with human stem cells. In the first phase, the embryonic undifferentiated stem cells were cultured by some specific chemicals to grow into auditory neurons. These were implanted into the gerbils ears and after a mere 10 weeks the first signs of success surfaced. During this time, the neurons grew fibers and reached the brainstem. To test if any hearing progress was made, the gerbils were subjects to sound wave while electrodes attached to their skulls measured brain waves for responses.

Thus, an estimated 46 percent increase in sensitivity was recorded, although the progress was rather inconsistent. A third A third responded exceptionally well, with some regaining 90 percent of their hearing, while another third showed almost no recovery at all. Still, for a human suffering from hear loss even the slightest progress could mean a shot at living a normal life. Can the procedure be transferred to humans in the first place?

Well, for one scientists have successfully managed to grow both auditory neurons and hair cells in stem cells cultures. The tricky part lies in the implant procedure itself. Unfortunately, hair cells require a very specific and precise orientation in the inner ear to function properly. Implanting hair cells precisely and safely is a great technical challenge, which many leading experts around the world view it as unreachable at this time.

“This is promising research that demonstrates further proof-of-concept that stem cells have the potential to treat a range of human diseases that currently have no effective cures. While any new treatment is likely to take years to reach the clinic, this study clearly demonstrates that investment in UK stem cell research and regenerative medicine is beginning to bear fruit,” said Dr. Paul Colville-Nash, Program Manager for stem cell, developmental biology and regenerative medicine at the Medical Research Council.

This latest research which shows promising results concerning stem cell treatment, coupled with an earlier independent research which used gene therapy to stimulate regeneration of hair cells in the cochlea, offers a much needed ray of hope to deaf patients around the world.


Hair cells located in the organ of corti, in the cochlea of the inner ear.(c) SPL / Photo Researchers, Inc

Deafness cured by gene therapy

Hair cells located in the organ of corti, in the cochlea of the inner ear.(c)  SPL / Photo Researchers, Inc

Hair cells located in the organ of corti, in the cochlea of the inner ear.(c) SPL / Photo Researchers, Inc

A stroke of pioneering science, researchers have managed to restore hearing to a significant level in guinea pigs by using gene therapy, bolstering hope for a similar procedure to cure human deafness in the future.

The therapy works by promoting the regeneration of hair cells in the cochlea, the part of the inner ear which registers sound. These hair cells act like tiny dishes that catch infinitezimal fluid motion and transmit them into nerve signals to the brain, which we typically recognize as sound. These tiny hairs are incredibly sensitive, and it’s common for them to deteriorate or even get completely distroyed when exposed to loud sounds, certain drugs or old age, ultimately.

“It’s the first time anyone has biologically repaired the hearing of animals,” says Yehoash Raphael at the University of Michigan in Ann Arbor, Michigan, and head of the US-Japanese team that developed the technique.

For their research, the scientists first destroyed the inner-ear hair cells in guinea pigs. Then they injected a specially engineered adenovirus, the key to the treatment. This virus is completely harmless and contains a  gene called Atoh1 or Math1, which gets infused to the cells inside the scala media, the chamber where the tiny hearing hairs lye. The gene then generates a signalling molecule known to orchestrate the development of hair cells in embryos.

“The recovery of hair cells brought the treated ears to between 50% and 80% of their original hearing thresholds.”

By all means, these are incredible results. Moroever, the researchers report that hair cells were generated from other cells lined in the scala media, meaning some cells had been turned into other cells. Incredible!

The researchers hope this therapy might be used in the future on humans, at least as a complementary measure for people already using hearing aid devices. Raphael says that the next experiments in guinea pigs will focus on this combination. However, guinea pigs are far different from humans. For one, the inner-ear is nested deep inside the skull for humans, making surgery extremely difficult*, and there’s always a big chance the immune system will reject the researcher’s engineered virus. Let’s hope for the best.

The researchers’ findings were published in the journal Nature Medicine.

 *edit: in the initial draft of this article I wrote that inner-ear surgery in humans is impossible, which is a false statement. This type of procedure is difficult, but possible. Many thanks to Paul Harris for the input.