This Better Hearing & Speech Month, New HRP Research Projects Commence

By Tara Guastella

In conjunction with Better Hearing & Speech month this May, I'm excited to share that HHF is funding, for the third consecutive year, new research grants for our Hearing Restoration Project (HRP) consortium. This year is exciting as our HRP scientists are finishing up the first of three phases of the Strategic Research Plan. This plan defines our road-map to clinical trials for a cure for hearing loss and tinnitus within a decade.

Many types of hearing loss result from damage to the delicate hair cells of the inner ear. Humans can't regenerate these cells-but in a game-changing breakthrough in 1987, HHF-funded scientists discovered that birds can. Over the last several years, the HRP scientists have produced new genomic datasets from fish and birds, which show regeneration, and mouse, which does not; these datasets now allow us to take the next steps in understanding which genes promote regeneration in some animals and which genes block it in others.

“The 2014 funded projects will continue to move us closer to our goal of inducing hair-cell regeneration in people, to produce a cure for hearing loss and tinnitus," shares Peter G. Barr-Gillespie, Ph.D., director of the HRP consortium. "I am incredibly pleased with the outcome of the work the HRP consortium members have been conducting over the last several years.”

We are renewing three projects from previous years as well as initiating four new projects, each moving us closer to a cure. There are also four new projects that have commenced on May 1. Here are the details about the new projects:

Led by Andy Groves, Ph.D., Tatjana Piotrowski, Ph.D., and Jennifer Stone, Ph.D., one of the new projects is focusing on bioinformatic analysis of genetic data collected throughout Phase I. Bioinformatics is a set of sophisticated computational tools that will allow us to compare genetic data from zebrafish, chickens, and mice. Since we know that zebrafish and chickens spontaneously regenerate their inner ear hair cells, we can compare their genetic data to that of mice, which like mammals do not regenerate hair cells. Once we know what genes, or series of genes (known as pathways), trigger regeneration in zebrafish and chickens, and which inhibit it in mice, we will have better targets for drug therapies that may be able to induce regeneration in humans.

Another new project building off of work started in Phase I is analyzing the inner ears of chickens. Chickens have a remarkable ability to regrow hair cells once they are damaged. The consortium members involved—Stefan Heller, Ph.D., Michael Lovett, Ph.D., Jennifer Stone, Ph.D., and Mark Warchol, Ph.D.—are using newly developed techniques to study how supporting cells react when neighboring hair cells die and which signaling pathways are activated or deactivated. They are also are determining if this new technique, known as single cell transcript analysis, can be used more broadly in analyzing regenerative capabilities.

Edwin Rubel, Ph.D., who is also known as the co-founder of hair cell regeneration in chickens, is working on the characterization of a mouse system in which the inner ear hair cells can be reproducibly removed from the inner ear without doing damage to other components of the inner ear. Such a "model system" would allow the systematic study of hair cell regeneration at any age and in live animals.

Finally, Alain Dabdoub, Ph.D. and Albert Edge, Ph.D. are collaborating on a project studying the signaling molecules in the Wnt pathway to better understand its role in regeneration. Wnt signaling has been shown to play a major role in stem cell biology, cell proliferation, and cell fate determination.

“As a person living with hearing loss, I am thrilled with the progress that the HRP consortium is making,” says Shari Eberts, the chairman of HHF’s board of directors. “We are funding the best hearing scientists, conducting groundbreaking research, and are on track to see a cure for hearing loss and tinnitus within a decade.”

Read more about all of the currently funded HRP projects and updates on progress from past research as well.

Will Research on Chickens Provide a Solution to Needing Hearing Aids?

By Aaron Rodriques

Researchers hope to develop hearing loss treatments by studying the regenerative capabilities inner ear cells in chickens. We discovered some interesting info on these little guys and hearing aids. 

An Alternative to Hearing Aids

Scientists are on the path of a new application that could provide a unique alternative to hearing aids. By studying hair cells found in the inner ears of chickens, researchers are in the process of creating treatments that cure hearing loss in humans, minimizing the demand for hearing aids in the future.

Chickens can regenerate inner ear cells that replace cells damaged from noise and other forms of physical trauma. All vertebrates except mammals can exhibit this phenomenon. 

"The key to restoring hearing in humans is to regenerate cells deep within the inner ear," said Shari Eberts, chairwoman of the board of directors of the Hearing Health Foundation, which is funding the research. "While humans cannot regenerate hair cells in the inner ear after they are damaged, chickens can. In fact, most animals other than mammals can regenerate these delicate cells, restoring their hearing spontaneously after damage."

Hearing Aids and the Hearing Restoration Project

The Hearing Restoration Project (HRP) involves researchers from more than 10 institutions including Harvard Medical School, who are studying chickens in order to find out how humans could possibly regenerate inner ear cells. 

Approximately 36 million adults in the U.S. have some kind of hearing loss, and 25 million have tinnitus, according to the National Institute of Deafness and Other Communication Disorders. The Hearing Health Foundation aims to manufacture a cure by 2024.

According to Eberts, researchers are studying fish and mice as well. Fish can regenerate hair cells like chickens, but mice cannot.

"By analyzing what genes allow for regeneration in fish and chickens, we can compare those to mouse genes to see where the differences occur," she said. "Once we have an understanding of what genes and sets of genes (known as pathways) play a role in allowing for regeneration in fish and chickens, and which inhibit regeneration in mice, we will have a clearer understanding of how to trigger regeneration in humans."

Animal Biology and Hearing Aid Design

Similar studies with different animal species have found them to have unique hearing capabilities that offer promising new innovations for hearing aid technology. This includes the impressive hearing abilities of the Greater Wax Moth, a tiny insect found in beehives, and the unique anatomy of the locust. Hearing aids based on structures found in nature are considered to have a “biomimetic design.”

This article was republished with permission from Audicus.

Can Plants Hear?

By Yishane Lee

As a friend of HHF, you are no doubt well aware that chicks, fish, and reptiles have the ability to regenerate their inner ear hair cells, an ability that means any damage to their hearing is corrected.

Mammals, including humans, cannot, and this is the core of what HHF’s Hearing Restoration Project is working to solve within the next decade—how we can translate the chick’s ability to regrow hair cells to humans, and as a result find a biologic cure for hearing loss and tinnitus.

Now comes news that it is not just the animal world that can hear. Plants can, too. A recent story by Michael Pollan in the New Yorker included this paragraph (italics mine):

“Plants have evolved between 15 and 20 distinct senses, including analogues of our five: smell and taste (they sense and respond to chemicals in the air or on their bodies); sight (they react differently to various wavelengths of light as well as to shadow); touch (a vine or a root ‘knows’ when it encounters a solid object); and, it has been discovered, sound. In a recent experiment, Heidi Appel, a chemical ecologist at the University of Missouri, found that, when she played a recording of a caterpillar chomping a leaf for a plant that hadn’t been touched, the sound primed the plant’s genetic machinery to produce defense chemicals. Another experiment, done in [Italian plant physiologist Stefano] Mancuso’s lab and not yet published, found that plant roots would seek out a buried pipe through which water was flowing even if the exterior of the pipe was dry, which suggested that plants somehow ‘hear’ the sound of flowing water.”

I find this absolutely fascinating. Could it be the plants “hear” via sensing sound vibrations—just like we do? And then they’re able to correctly correlate these vibrations to the category of friend or foe—again, just like we do? To hear the plant biologists in the story put it: Yes, it’s entirely possible, and even likely.

The article raises interesting issues of why animal-based biology deserves primacy, and whether a typical (animal) brain is needed for something to be considered intelligent. In addition to reading the piece, which I highly encourage you to do, there is a TED Talk by Mancuso, if you want to learn more.

We can learn much from plants. The promise of the Hearing Restoration Project is that we can also learn much from chicks, fish, and reptiles. Indeed, there has been early success with hair cell regeneration in mice.

Support the search for a cure for hearing loss and tinnitus within a decade.

Hybrid Cochlear Implants Blend High and Low Frequencies for a Fuller Sound

By Yishane Lee

“Electro-acoustic stimulation” is a mouthful, which may explain why “hybrid cochlear implant” is becoming shorthand for the latest thing in cochlear implantation.

What is a hybrid CI? It is a cochlear implant that makes use of residual hearing in the cochlea, with the goal of preserving it. Lina Reiss, Ph.D., of the Oregon Health and Science University, is a 2012 and 2013 Emerging Research Grant recipient conducting research in hybrid CIs, and she cowrote a piece in our Winter issue of Hearing Health introducing us to this exciting development.

The hybrid is especially promising because it is ideal for people with age-related hearing loss. As the story says:

“The hybrid CI helps people with high-frequency hearing loss while retaining their natural, residual hearing in the low frequencies. A high-frequency hearing loss, like that common in age-related hearing loss, makes consonants difficult to discern. The hybrid CI provides high-frequency information electrically and restores consonant perception. The residual low-frequency acoustic hearing helps ‘round out’ the artificial hearing provided by the CI, and together this gives the user a fuller hearing experience.”

Dr. Reiss collaborated with Christopher W. Turner, Ph.D., of the University of Iowa. Dr. Turner has been involved from the beginning in the development, assessment, and optimization of the hybrid electrode, with more than 20 publications on the subject since 2003, and he is a former HHF grant recipient as well.

One risk of hybrids is losing the low-frequency hearing entirely after implantation. A slightly longer electrode length—shorter than a traditional CI but longer than the initial hybrids—allows the implant to function like a traditional CI if the acoustic hearing is lost. It is undergoing clinical trials and received preliminary FDA approval last November, which is a very good sign.

I asked Dr. Reiss how she became a researcher, and specifically how she came to study cochlear implants. She says:

“I was always interested in science because my father was a scientist. In high school and college, I had some very stimulating research experiences in biological research. I also have a severe-profound hearing loss, and so have a personal interest in auditory research.

“After my sophomore year, I was lucky to obtain a summer research internship working in Eric Young’s auditory neurophysiology laboratory at Johns Hopkins University, where I studied how auditory nerve fibers encode speech sounds. I ended up doing my Ph.D. in that lab, studying how the dorsal cochlear nucleus encodes sound localization cues.

“However, I wanted to do more translational research, so ended up doing a postdoctoral fellowship with Chris Turner at the University of Iowa, where I got involved with the hybrid CI clinical trials. We got a lot of very interesting data with the hybrid CI study, particularly regarding brain plasticity, and there were many other interesting research directions to go on to from there.”

At HHF, we’re definitely excited to see where Dr. Reiss’s curiosity leads.

Meeting of the HRP at ARO Midwinter Meeting

By Tara Guastella

Last Saturday, the second meeting of the year for the members of the Hearing Restoration Project (HRP) consortium occurred. In conjunction with the Association for Research in Otolaryngology (ARO) Midwinter Meeting, the HRP meeting took place in sunny San Diego—a much-needed respite from the frigid temperatures many of us around the country are encountering!

This HRP meeting was unique as it was the first time the Scientific Advisory Board (SAB) of the HRP was invited to attend. During the meeting, scientists for each of the currently funded HRP projects made brief presentations of their research progress. Following each presentation, other consortium members and SAB members took part in lively discussion identifying new ideas and opportunities for collaboration.

The group also had an in-depth discussion about the use of bioinformatics. These are sophisticated computational tools that will allow HRP consortium members to analyze large sets of cross-species data. Bioinformatics is a crucial part of the work of the HRP consortium as it will help identify and compare which genes allow for the natural regeneration of hair cells in animals like chickens and fish, and which genes inhibit this regeneration in animals like mice.

Once we have a clearer understanding around the genetics that allow for hair cell regeneration, we can begin to move into Phase II of our Strategic Research Plan. Phase II centers around using the knowledge gleaned through bioinformatic analysis to trigger hair cell regeneration in mammals—getting us one step closer to a cure for hearing loss and tinnitus.  

Stay tuned for updates on newly funded HRP projects to be announced this spring!

What Do the Lunatic Fringe, a Cheap Date, Groucho Marx, and the Sonic Hedgehog Have in Common?

By Yishane Lee

At a presentation Hearing Restoration Project scientist Neil Segil, Ph.D., made to a small audience at the HHF offices earlier this year, I was surprised (and delighted) to learn that a gene had the name of Lunatic Fringe—which is not to be confused with the Manic Fringe or the Radical Fringe. Dr. Segil mentioned the gene because it can affect the Notch signaling pathway, a form of cell communication that creates mosaic patterns of different cell types, like the kind we see in the inner ear for hearing. I wondered, how did the gene get this name?

The privilege for people who discover things is that they get to name it—be it a star, mountain, or gene. And the scientists who worked on genetically mapping the fruit fly, which has been studied for over a century, have a sense of humor.

Besides the fringe genes, there are these fruit fly genes that have been found or created: the Tinman refers to a gene that makes it hard to develop a heart; the Groucho Marx refers to a gene that produces excess facial bristles; the Cheap Date gene means the fruit fly is extra-sensitive to alcohol; the Ken and Barbie fruit fly lacks genitalia; and fruit flies with the I’m Not Dead Yet (INDY) gene live longer than usual. (See a list of funny fruit fly gene names.)

The problem, though, is that we discover we actually share quite a lot of ancestry—and therefore, genes—with the fruit fly, including those that cause hereditary diseases, telling a patient that he has a genetic condition related to a mutation in the Lunatic Fringe gene is not going to, well, fly. (Two faulty copies of the Lunatic Fringe gene, which encodes the development of the limbs and other parts of the body, leads to spinal defect known as spondylocostal dysostosis.)

So while these catchy names and the conditions they refer to are easy to remember, a few years ago the Human Genome Organization (HUGO) gene naming committee was petitioned to change them. And, faster than you can say Sonic Hedgehog (another gene name that was changed), the Lunatic Fringe—at least officially—became the LNFG.

Read more about genes related to hearing loss, including the HRP’s use of next-generation DNA sequencing.

Tell us what your favorite gene name is here in the comments!

Ears: The New Fingerprints?

By Tara Guastella

All ears are the same, right? Wrong.

Ears are actually unique to each and every person, so much so that they are comparable in uniqueness to the fingerprint. Research has even suggested that ears may be a more effective identification tool than a fingerprint through the use of a new “image ray transform” technology. This technology shines beams of light on the tubular features of the outer ear, creating an image from the way light reflects off the ear’s curves.

What makes the ear so unique? One’s ears are fully formed at birth and age gracefully over time, making them an ideal body part to confirm identity. Fingerprints can change due to the development of calluses from repeated labor which can make them less reliable.

In almost every crime scene TV drama, you’re likely to see characters dusting for fingerprints. When we will see them dusting for earprints? Well, I guess it’s a lot less likely that your average criminal is pressing an ear against an object while committing a crime. Yet in 1998, the first murder conviction on the basis of ear identification occurred in England. The convicted suspect pressed his ear up against a newly washed window in the house (where the murder took place) to listen for movement.

Airports also regularly use biometric facial recognition programs in their security programs. The addition of earprints to this type of security could also prove a valuable way to identify travelers as well as any potential threats.

Earprints come with limitations when it comes to identification, however. Ears can be altered in shape through plastic surgery or from an accident. Wearing earrings or eyeglasses or having hair pushed behind the ear can also alter the shape of an earprint.

While an earprint will likely will not substitute the fingerprint in terms of identification capability, it could be a valuable addition for solving mysteries, saving lives, and likely many other uses.

Do Chickens Hold the Key to a Cure for Hearing Loss?

Chickens have the amazing ability to restore their own hearing, and this trait is inspiring a nonprofit organization in their search for a cure for hearing loss in humans.

The Hearing Health Foundation’s “Chirp the News” video features the group’s new mascot: a baby chick. Locked within the ears of this chick is the potential to restore hearing and cure tinnitus, or ringing in the ears. According to the National Institute on Deafness and Other Communication Disorders, about 36 million adults in the U.S. have some form of hearing loss, and 25 million are affected by tinnitus.

“As someone who lives with hearing loss every day, I am personally thrilled with the prospects for a cure,” said Shari Eberts, chairman of the Hearing Health Foundation’s Board of Directors, in an email to Healthline. “Life with hearing loss can be frustrating. Sometimes you miss the joke when everyone else is laughing, and sometimes you miss important information because you don't hear it. Supportive family and friends can make living with hearing loss easier, but a genuine cure would be life changing.” 

The Chicken’s Magic Ears

The secret to the chicken’s auditory magic is that supporting cells in its inner ear can replace hair cells that have been damaged by loud noises or other causes.

And chickens aren’t the only animals that can restore their own damaged hearing. All vertebrates other than mammals can do the same. And preliminary research has shown that mice can regain some of their hearing using supporting cells that turn into hair cells—in the lab, at least. 

Researchers supported by the Hearing Health Foundation hope to find a way to coax the supporting cells in the inner ears of people to transform into functional hair cells. Their goal is to have a cure within a decade.

The 10-Year Road to a Cure

For people with hearing loss, waiting a decade for a cure can seem like a lifetime. But in the world of research, this is a very short time to travel from initial scientific discoveries all the way to successful clinical trials in humans.

To speed the research along, the Hearing Health Foundation is supporting a collaboration known as the Hearing Restoration Project (HRP) that involves researchers from more than ten institutions, including Harvard Medical School.

To find a successful cure for hearing loss, researchers have plenty o work ahead of them—including identifying how supporting cells in the chicken's ear turn into hair cells, as well as finding potential compounds or drugs that can make this happen in people.

Eberts is optimistic that the project will hit its mark, and so is Ed Rubel, a professor of hearing science at the University of Washington and a member of the project team.

“With sufficient funding,” he says, “the consortium can discover effective pathways and hopefully some lead compounds to promote hair cell regeneration in the mammalian inner ear in the 10-year time frame.”

Many Eggs in Many Baskets

In his lab at the University of Washington, Rubel is working on one piece of the puzzle that may one day lead to hair cell regeneration in people. 

“The project on my own has to do with developing a new mouse model to test the pathways and, eventually, the drugs that come out of the HRP,” he said.

The mice developed in his laboratory will be shared among members of the consortium, so they can avoid having to develop their own mice. This kind of sharing is an important aspect of the collaboration, something that Eberts expects will save time and money.

For Rubel, working with the HRP has other benefits.

“The wonderful thing about the consortium,” he says, “is that it includes only people who really want to play in that kind of sandbox—that want to share information, share early-stage information, share the other things that they’re doing in their laboratories, and work together.”

As a person with hearing loss, Eberts supports the push to highlight the project's potential.

“Even though we are in the early stages of the research, we think it is very important that the public learn about our efforts,” she said. “We want them to know that there is hope for a cure and that there are researchers who consider curing hearing loss and tinnitus to be their life’s most important work.”

This article was repurposed with permission from Healthline.

You Can Hear, Thanks to the Darwin Fish

By Tara Guastella

Photo by lapradei/Flickr

I never thought that fish would be an evolutionary ancestor to humans. Monkeys and chimpanzees, yes—but fish?

It turns out that a certain fish, known as Polypterus and related species, have tiny holes in the top of their head called spiracles. A team of researchers in California recently showed how a small valve opens a bony lid over these spiracles that allows air to be sucked in and pumped out when the fish surface.

Strangely enough those same holes allowing the fish to breathe have modified themselves over time to become Eustachian tubes. Enabling us to hear, these tubes are small passageways on either side of the head that connect the upper part of the throat to the middle ear. They supply fresh air, drain fluid, and keep air pressure between the nose and the ear at a steady level.

Hearing in early amphibians developed from the spiracles adapting to become the tympanic membrane (also known as the eardrum), a thin cone-shaped membrane that separates the external ear from the middle ear. The tympanic membrane is similar to skin and transmits sound to the brain through the stapes, the tiniest bone in the body.

Interestingly, the stapes evolved from a long bone, known as the hyomandibular bone, that braced the lower jaws of sharks and other early jawed fish. This bone eventually shrank in size to form the stapes.

The other two inner ear bones alongside the stapes—the malleus and the incus—also formed from bones that braced the articulation of the upper and lower jaws. These bones decreased in size and became restricted to the inner ear. So, these three little bones that enable us to hear derived from the larger jaw bones of ancient fish.

If not for the evolutionary experiments of these prehistoric fish breathing air through the top of their heads, humans may never have evolved a keen sense of hearing.

Now that you know how our hearing evolved, learn more about how hearing works and how the human ear processes sound. Watch our captioned How Hearing Works video.

How Can a Chicken Cure Hearing Loss & Tinnitus? Find out in our new PSA!

By Tara Guastella

I’m so excited to share that we have recently launched a new Public Service Announcement (PSA): Chirp the News! The PSA introduces HHF’s new mascot, a baby chicken.

Why a baby chicken?

The key to restoring hearing in humans is to regenerate cells deep within the inner ear. In fact, most types of hearing loss in humans results from damage to these cells, called hair cells. While humans cannot regenerate hair cells in the inner ear after they are damaged, chickens can. In fact, most animals other than mammals can regenerate these delicate cells, restoring their hearing spontaneously after damage.

This knowledge is the basis for our Hearing Restoration Project (HRP). The HRP is a consortium of over a dozen top scientists from across the world working collaboratively to take what we know happens in chickens and translate that to people. Our HRP scientists estimate clinical trials testing a genuine, biologic cure for hearing loss can occur within the next decade. Since over 90 percent of tinnitus cases occur with an underlying hearing loss, a cure for hearing loss is also likely the key to a cure for tinnitus.

Most scientific research is conducted in isolation: one researcher or one lab trying to solve a major health issue. Our unique HRP consortium model is breaking the mold by encouraging our scientists to work as a team sharing data, tools, resources, and ideas. By working collaboratively, the timeline to a cure is expedited: five times as fast with the power of collaboration.

We won’t be able to get to a cure for hearing loss and tinnitus without your help—please donate today and be a part of the cure.