Dr. Peter Santa Maria, MD, PhD, opened the Eye & Ear Foundation’s September 13th webinar, “Restoring Hearing and Regenerating Hair Cells” with a quote from Helen Keller: “Blindness separates people from things, deafness separates people from people.” These words hit home for the Division Chief of Otology & Neurotology and Vice Chair of Clinical and Translational Research, because they illustrate why the group’s work is so important. Hearing loss is an invisible disability that can change people and influence their ability to connect and communicate with others.
Troubling Numbers
One in three people over the age of 65 have hearing loss. It is the second most common illness in the elderly and the third most prevalent health condition. It is estimated that there will be 500 million people with disabling hearing loss worldwide by 2025. Hearing loss results in $750 billion in costs.
Impact
There is a direct link between hearing loss and falling. If you are not hearing and therefore not aware of your surroundings as much, particularly if balance is affected, this can have an impact on your life. Hip fractures in the elderly, for example, are associated with a very high mortality rate.
The impact that hearing loss has on cognitive function cannot be understated; it is the largest variable of cause that could lead to cognitive impairment as we age. Nine percent of modifiable risk of Alzheimer’s is attributed to hearing loss.
Hearing loss intervention could reduce the cognitive load of processing degraded sound, provide increased brain stimulation, and improve social engagement.
Barriers
However, there are barriers to the uptake of hearing care in adults, such as cost/affordability, awareness and understanding, access to services and technology, and technology design and utility.
Stigma is another barrier that still exists. “If I wear glasses, I’m considered smart,” Dr. Santa Maria said. “If I wear hearing aids, the old stigma was that you’re growing old.” The stigma is decreasing today. Dr. Santa Maria moved to Pittsburgh from the Bay Area, where most young people were excited to be wearing hearing aids. In a high technology area, everyone wears some sort of earbuds or wearable, so adding a hearing aid is not a big deal. “But it is still a barrier we need to break through,” he added.
It is actually cool now to wear something around your ear, Dr. Santa Maria pointed out. Instead of small earbuds, people are going for large, visual headphones. “We just need to think a little bit differently about hearing loss,” he said. “It is not a disability anymore.”
Hearing Aid Evolution
From the first models of hearing aids, trumpet-style, to sleek changes in design, hearing evolution has come a long way. As a doctor, Dr. Santa Maria said he does not even notice people wearing them anymore. Now they come in a lot of different shapes and sizes. They can be completely hidden inside the ear canal and invisible to behind the ear. A couple of innovations include Lyric, which is hidden completely inside the canal, and Earlens, which uses light or magnetic amplification to get a better high frequency response. Lots of innovations are still happening, and things are becoming cheaper and more available, even online.
Cost
Hearing aids are still exorbitantly priced. A pair of glasses can cost $196, yet a hearing aid is $2700 or $5400 for a pair. The average social security benefit is $16,461/year, and the maximum social security benefit for retiring at age 70 is $32,000/year. Products are sold at 20 times the cost. “$6,000 for a pair [of hearing aids] is unsustainable,” Dr. Santa Maria said. “The hearing aid industry is ripe for disruption.”
Now people can buy PSAPs (personal sound amplification product) online. Most are self-fitting and can cost as little as $50. More custom fit ones can be purchased from Best Buy and major chains, where costs can get in the hundreds. There is something that will hopefully meet most people’s needs.
The convergence of medical devices (hearing aids) and consumer electronics (“hearables”) can do more than provide sounds. They can measure heart rate and body temperature, and count steps, among other things. As we move into the wearable generation, Dr. Santa Maria predicted that we will see many more innovations that will make hearing aids more accessible to the average person. If someone falls while wearing a hearing aid, for example, it could potentially send a signal to a loved one.
Cochlear Implants
Graham Clarke is credited for helping invent the cochlear implant in 1978. It is a device placed during surgery that has a little wire electrode that goes around into the inner ear and converts acoustics into electrical sound. We now have decades and decades of research on the cochlear implant, which is not a new device anymore. “These have changed the way that we manage hearing loss for people who can’t wear hearing aids,” Dr. Santa Maria said.
The Pittsburgh Hearing Institute
On the horizon is the Pittsburgh Hearing Institute, which will bridge the gap between basic and clinical research with translational research. People are trying to figure out how to get discoveries into the clinic. There are lots of connections to developing countries, like Mozambique. Dr. Palmer is leading community work, and people like Dr. McGovern are trying to solve problems in hearing loss.
Restoring Hearing
Melissa McGovern, PhD, Assistant Professor and molecular biologist who investigates hearing restoration, talked about the basic science she does in her lab. First, she described the cochlea, a coil-shaped structure that is part of the inner ear and detects sound. It contains several intricate components, including the organ of Corti, which has sensory hair cells – which detect sound and tell the brain about it — and adjacent supporting cells. Loss of hair cells causes hearing loss.
“The idea of a potential future gene therapy is to figure out how we can regenerate these sensory cells, these hair cells, from supporting cells or other cells in the environment,” Dr. McGovern said.
The immature mouse cochlea can spontaneously regenerate. This time frame corresponds to the end of the first trimester in human development, so this is extremely early, and the organ cannot actually detect sound at this time. The mature mouse cochlea does not naturally regenerate, and this is the same for all mammalian species that have been studied.
Certain medications can cause the death of these hair cells, along with loud noises and natural aging. The hearing loss that results in the death of hair cells is permanent.
Dr. McGovern has been investigating genetic reprogramming to create new hair cells. Different cell types only express certain genes, so the question is, “How can we activate hair cell identity in a non-hair cell, such as a supporting cell, to convert into hair cell identity?”
Transcription factors like Atoh1 control cellular identity by regulating gene expression. Atoh1 expression in the immature cochlea induces hair cell formation, but expression of Atoh1 does NOT reprogram supporting cells in the mature cochlea.
Transcription factors often work together. It is possible, if multiple transcription factors are expressed at the same time (like Gfi1, Pou4f3, and Atoh1 – factors very important for the development of hair cells), then we can overcome these genetic barriers and further reprogram. Supporting cells require all three of these factors for reprogramming.
One thing Dr. McGovern noticed during this project is that only a small number of cells that were targeted actually converted into hair-like cells. “What could potentially be stopping other supporting cells from being reprogrammed?” she asked. Signaling from hair cells to supporting cells control spontaneous regeneration in the immature cochlea. But are cochlea hair cells still controlling cell fate in the mature adult cochlea? She found that more supporting cells can be reprogrammed when the original hair cells are gone.
In summarizing cell reprogramming, Dr. McGovern said that in control, where the hair cells are all still there, the hair cell genes that need to be activated for the cell to become a hair cell are likely inaccessible. If you first kill the original hair cells, these genes seem to become more accessible. If the three transcription factors are expressed, they can convert the sensory supporting cells into hair-like cells. “We were very excited by this because it suggests is that any potential gene therapy that is going to involve these three transcription factors is going to be able to reprogram supporting cells following the hair cell loss that causes hearing loss,” Dr. McGovern said.
Are other cells in the ear a potential target for reprogramming? The flat epithelium is found in the cochlea following some forms of severe damage. Both hair cells and supporting cells are lost, and therefore the supporting cells are not available to regenerate hair cells. One leading hypothesis about how the flat epithelium is produced is that the cells adjacent to the organ of Corti migrate in and form a scar that replaces the organ of Corti. “So, if the cells that create the flat epithelium can respond to transcription factor reprogramming, this could potentially be a therapy for people who have lost both hair and supporting cells,” Dr. McGovern said.
Dr. McGovern called the cochlea like a Rube Goldberg machine. Her lab focuses on whether supporting cell genes can be turned off to enhance regeneration, and what the “brakes” are that prevent complete reprogramming. They are also determining whether a delivery method can be developed that will be clinically relevant. They still need to develop therapies that can actually target supporting cells. This is in the initial stages of development, and the lab is collaborating with another lab in the Pittsburgh Hearing Research Center.