Adult-onset hearing loss is a form of progressive deafness that affects a third of adults over the age of 60. While hearing loss can have a number of causes, about half of the early-onset cases (those occurring before age 60) in developed countries are related to a difference in one or more of a patient’s genes.
Now, a wide-reaching collaboration at Penn Medicine is resolved to developing a novel gene therapy for adult-onset hearing loss by better understanding the genetics of the condition.
Genetic hearing loss variants that cause only hearing loss, a condition are known as non-syndromic. Those that trigger issues throughout the body in addition to hearing loss, are referred to as syndromic.
Whatever the classification, the genetics of adult-onset hearing loss have received less attention from researchers to this point, despite substantial advances in the understanding of genetics and its implications for diagnosing hereditary hearing loss in children.
This dichotomy and its implications are particularly clear to Tiffany Hwa, MD, who was named the Clinical Director of the Penn Center for Adult-Onset Hearing Loss in July 2023.
“Our sense is that there’s this population lost to science because past efforts have, rightfully, been so focused on child-onset hearing loss,” Dr. Hwa observes. “In some of these cases, it seems clearly hereditary. And giving patients a negative result on their genetic hearing loss panel feels like you’re gaslighting them. Their mom, dad, brother, and uncle, all these different people in their family have hearing loss at a relatively young age, and yet we don’t we don’t have an identified gene to help them understand their experience.”
The Penn Center is the first dedicated to the genetics of adult-onset hearing loss. It is a collaboration between Penn ENT, Penn Translational Medicine and Human Genetics, and the Penn Medicine BioBank. Patients who meet the criteria for early-onset hearing loss, or whose family history indicates a pattern of hearing loss suggestive of a genetic cause, are referred to Penn Translational Medicine and Human Genetics, where a genetics counselor thoroughly reviews their medical and family history with them. From that session, a hearing loss panel is developed and presented to hearing loss specialists at a monthly meeting.
Every panel presented at this meeting for discussion is reviewed by a team of specialists, including a genetics counselor and Dr. Hwa, as well as Douglas J. Epstein, PhD, Professor of Genetics at the Perelman School of Medicine at the University of Pennsylvania, and other geneticists, members of the BioBank, audiologists, otologists, and experts in computational biology.
“We’re investigating this from a number of different angles,” Dr. Hwa says.
Insurance coverage for the hearing loss panels can be an issue. Some insurance companies do not cover the hearing loss panel, and those that do include only panels that evaluate known genetic mutations. To prevent this from being an obstacle for everyone else, including those with no insurance, the Center negotiated to keep the cost of the panel relatively low.
Dr. Hwa and her colleagues have also been scanning the BioBank for “genetic mutations of interest.” But the search has presents several issues. Just because individuals have a mutation the researchers have homed in on, for example, doesn’t mean they’ve begun to experience hearing loss, or that they’ve had a hearing test recently.
“It’s more like a snapshot,” Dr. Hwa says. Still, she’s optimistic.
“We needed to start somewhere,” she says. “We’re figuring out what works, trying to solve the problems as they arise,. All it takes is one discovery, and then we can build from there.”
Limited English Proficiency and Hearing Loss
Separate from her work with the Center, Dr. Hwa has been exploring provider- and patient-facing remedies for hearing healthcare disparities for patients with limited English proficiency (LEP). She says she was drawn to their plight, in part, because she’s the child of first-generation immigrants.
It’s difficult to know how large this population is. The United States Census Bureau reports that 8.3 percent of the population over the age of five has LEP. But there is no data available on how prevalent hearing loss is among this demographic.
Penn makes available video interpreters for patients with LEP, but Dr. Hwa, who speaks English, Mandarin, and Spanish, says she’s often wondered how much patients with hearing loss are picking up in these three-way consultations.
Of even greater concern to her is the worldwide protocol for establishing a patient’s need for hearing aids or cochlear implants. A segment of the test administered by an audiologist examines the patient’s speech recognition capability. The audiologist says a series of words and, one by one, the patient repeats them back.
“If the patient speaks Spanish and we happen to have a Spanish-speaking audiologist, that will work,” she says. “But in almost every other instance–Hindi, Bengali, Russian, anything other than English or Spanish, really–our audiologist is dependent on either a family member or an interpreter to assess the patient’s accuracy. And this is the test that we’re using to make life-changing recommendations.”
Dr. Hwa is approaching these issues from an array of angles. To better appreciate how much the current models for care may need to change, she’s been reviewing previous research to determine whether people with LEP and hearing loss have been included in research studies. Their absolute exclusion would mean their outcomes aren’t represented in the literature.
For a soon-to-be published paper she coauthored, Dr. Hwa asked providers how they use the tools available to them to navigate these issues, and what types of equipment would improve care in this realm. For another paper in the works, she and her coauthors appraised the value of certain kinds of mainstream artificial intelligence applications as clinical tools.
“Can I, for instance, speak into Google Recorder and have it produce Hindi in written form in a way that has a high level of fidelity to what I’m saying?” Dr. Hwa says, adding that these seem like solvable problems. “They just need somebody to rally the resources that are already available and develop that technology in a way that can help these patients sitting right in front of us.”
Improving the Music Experience for Cochlear Implant Recipients
As a medical student at the Columbia University College of Physicians and Surgeons, Dr. Hwa began assisting in a modest-size study, led by Anil Lalwani, MD, with an ambitious goal: to enhance music enjoyment in cochlear implant recipients. After she was named to the faculty at the Perelman School of Medicine, Dr. Lalwani agreed to begin a parallel program at Penn. Today, the study also encompasses a Stanford University-based music technologist, Dr. Lloyd May.
“Cochlear implants are incredible, life-changing devices for speech,” Dr. Hwa says, “but we’ve known for quite some time–over 20 years–that they’re really not great for music. Up to two-thirds have reported being disappointed with the way music sounds through the implant.
“It’s easy to downplay the importance of something like that when you’ve managed to restore speech function for a cochlear implant recipient, but experiencing music is inseparable from the human experience,” she adds. “So, a lot of really great thinkers have been looking at this problem.”
Among much else, these experts have explored hardware and software modifications to the implant. More recently, they’ve begun augmenting the music itself, which seems to have shown the most promise, and Dr. Hwa senses they’re close to a breakthrough. In which case, translating their work to a real-world application becomes the next big challenge.
If it takes the form of an equalizer function, would the likes of Spotify or YouTube Music, the two largest music streaming services in the US, be willing to adopt it, even though it’s not likely to generate much, if any, revenue? Or would it need to be implemented by the makers of the implants as an independent mobile application?
In order for either to become a consideration, Dr. Hwa says she and her fellow researchers first need to compile a robust set of data. In light of their recent headway, this step appears to be imminent.