Mass Eye and Ear Researchers Make Strides Toward Drug Delivery for Hearing Loss Treatment

Ready for some progress in the search for a cure for hearing loss? Yeah, me too.

I came across an article on how researchers recently used a drug-like cocktail to regenerate hair cells for hearing loss. The findings were published in an April 2023 study in the scientific journal PNAS.

Sounds promising. But as a layperson, it can be hard to understand what that means, and if it’s actual progress.


So I reached out to the study’s principal investigator, Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Labs at Mass Eye and Ear in Boston. Dr. Chen graciously replied to my questions about his findings. 


In a nutshell, this study is the first of its kind to show that drugs may one day be able to be used to regenerate hair cells in a clinical setting (i.e. a doctor’s office) — and some of the existing tools researchers already have may help to speed up development. In the future, the drug cocktail may be used to treat noise-induced or age-related hearing loss, or in combination with gene therapy to restore hearing in people with genetic hearing loss.

1. How are your findings different from previous research on potential treatments for hearing loss?

In the previous study, we showed that it is possible to regenerate hair cells in the fully mature mammalian inner ear by genetic manipulation. The current study is to demonstrate that similar hair cell regeneration can be achieved by a combination of drug-like molecules, which is a major step for us to move the work towards the clinic.

This is not to say we have solved all the issues. We now focus on using the new approach to restore hearing in deaf mice, and all the information will be necessary for future clinical development.


2. What most surprised or excited you about the findings in this study?

The most surprising part is that some of the molecules we use to regenerate hair cells have been used in patients (VPA, LiCl) or the technology is mature (for siRNA in humans including Alnylam’s drugs), so we may benefit from the mature technology to speed up our work toward the clinic.


3. What are you hoping these findings will lead to in terms of potential genetic therapies for hearing loss?

If hair cell regeneration ultimately results in the treatment of hearing loss in patients, it potentially could be applied to the largest patient population with hearing loss including people suffering from age-related and noise induced hearing loss.

For genetic hearing loss, while regeneration alone may not be sufficient, it can be combined with gene therapy that is progressing rapidly as treatment. For many forms of genetic hearing loss due to hair cell damage or loss, gene therapy alone will not be sufficient due to the loss of a large number of hair cells. In this situation, we can regenerate hair cells and perform gene therapy at the same time as the treatment. The gene therapy approach is part of the hair cell regeneration in our study in which Atoh1 is delivered by adenovirus.

4. How can people with hearing loss help support hearing loss research like the type you’re doing?

There are many ways for people with hearing loss to support and speed up our work. Patients should first be properly diagonalized so we know what type of hearing loss they have (e.g. genetic, noise-induced, viral infection or age-related). This will serve as an important resource for potential candidates for future clinical trials.

Patients could join different organizations (e.g. the Hearing Loss Association of America) to help themselves and other people with hearing loss.

Of course, making donations is one of the most effective ways to help our work. I cannot emphasize enough how philanthropic support has helped our work enormously and will continue the trajectory till we develop the treatment.

We are truly excited about the future and will do all we can to get there as soon as we can.

Society Says Hearing Loss Doesn’t Matter: Part 1

Even though I’ve lived with hearing loss for over 35 years — and our world is supposedly getting more evolved — it’s still surprising to me when I come across evidence of how little regard society has for hearing loss, its ramifications, and for people who suffer from it.

Consider the following example, recently highlighted by the Hearing Health Foundation: In March, the U.S. Preventive Services Task Force (USPSTF) recommended against screening older adults for hearing loss. The organization “concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for hearing in older adults.”

Um, what?! Pun intended.

In the United States, 1 in 2 adults who are 65 years or older have a hearing loss. Not only that, but about 25 percent of those hearing-impaired adults don’t even know they have hearing loss (and others probably know but don’t want to deal with it).

There is a prevailing idea in our society that hearing loss isn’t a big deal; it’s a nuisance for others to have to repeat themselves, or communicate with the hearing-impaired, but little regard is given to how it impacts the person experiencing it. Studies show that untreated and undiagnosed hearing loss is associated with dementia, falls, depression, and social isolation. That’s not even getting into the profound impact it can have on quality of life, employment, relationships, and other critical factors.

The USPSTF’s disregard for hearing screening is indicative of a few things: First, that hearing loss is still not taken seriously. Second, they aren’t recommending screening because the current treatment — hearing aids — isn’t utilized by the majority of people with hearing loss, and it isn’t covered by most insurance, making the cost out-of-reach for many Americans.

It’s not a big secret that health insurance companies aren’t really designed to keep us healthy; they are for-profit companies that have raked in billions in profits, even during the pandemic. I doubt they want to cover hearing screenings in older adults, because then they’d have to start covering hearing aids, too.

When will hearing loss be given the urgent attention it deserves? When will the government, health officials, and insurance executives start to treat hearing impairment like a real issue? Not anytime soon, it seems.

Akouos: A Bold Step Towards Treat Hearing Loss with Genetic Medicines

Last week, Akouos, Inc. (pronounced Ah-KOO-os), a Boston-based biopharmaceutical company, was granted both Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) by the FDA for AK-OTOF, a gene therapy the company is developing to treat hearing loss caused by mutations in the otoferlin (OTOF) gene. The company is expecting to submit an investigational new drug application in the first half of 2022. These events are significant not just because they could lead to the first clinical trial to treat a genetic form of hearing loss, but also because an orphan drug and rare pediatric disease designation could mean that clinical development of the therapy can go faster.

I had the pleasure of learning about Akouos’ work from Manny Simons, PhD, the president and co-founder of the company. While some companies in the hearing research space are focused on treating noise-induced hearing loss or preventing hearing loss caused by ototoxic drugs, Akouos was founded with an initial focus on treating genetic hearing loss. “Genetic hearing loss is underappreciated and under the radar,” says Dr. Simons. “Even in our early fundraising, it was sometimes hard to convince investors of the prevalence of genetic hearing loss.” While hearing loss can be caused by many factors, 50 to 60 percent of hearing loss in babies is caused by genetic mutations, according to the Centers for Disease Control and Prevention. There are more than 150 genes that have been identified that can be tied to hearing loss, and countless more to be discovered.

The Promise of Gene Therapy

Historically, delivering medicines to the inner ear has been a challenge, and the tiny, tightly-enclosed cochlea – which transmits sound to the brain – was difficult to study. But Akouos saw promise in using gene therapy to address hearing loss. “We wanted to focus on forms of hearing loss where the biology and mechanisms were understood,” Simons explains. “This potentially gives us a higher probability of treating genetic hearing loss and addressing the root cause.”

Akouos chose to work on gene therapy first for OTOF because “everything else in the ear is intact – the connection between nerve cells is still there,” Simons explains. It affected just one thing in the ear: otoferlin, a protein involved in hearing. People with the condition have severe-to-profound hearing loss from birth. The gene therapy treatment is designed to return a healthy copy of OTOF, potentially taking a person from profoundly deaf to having functional hearing.

Listening to Those With Hearing Loss

Akouos is committed to keeping the concerns of those with hearing loss at the center of what they do. “We want to hear from the community,” says Simons. “The more we can be doing to have a bigger impact, the more effective we can be, even as the company grows.”

To that end, Akouos is sponsoring a genetic testing program called Resonate, which provides free genetic testing to people in the U.S. who have a diagnosis or medical history of auditory neuropathy.

In addition, you can subscribe to Akouos’ newsletter for company updates, and sign up for press releases to get the latest news. You can also follow Akouos on LinkedIn and Twitter.

Hearing Loss Help for Seniors

Whether you’re new to living with hearing loss or are an old pro, it can be tough to find reliable information about it. It’s always surprised me that for a health condition that affects so many people, there isn’t more about hearing loss written on the web.

Consolidated, practical information on hearing loss can especially be challenging for seniors — who are the population most likely to experience it. “Many seniors find themselves struggling with newly developed hearing loss, but it is an issue that can be helped with the right support and information,” says Sarah Martell, a web advocate at More Connected, an outreach organization that focuses on resources for those with under-served needs such as hearing loss. “In addition to the technology that is available, there are matters of lifestyle, financial support, and health considerations to be addressed,” she says.

Two comprehensive resources Ms. Marshall recommends are:

  • Help Advisor: A website for seniors, which includes a guide to treating and living with hearing loss
  • Medicare Advantage: Tips and resources for Medicare beneficiaries suffering from hearing loss

As with any health condition, having the right resources for hearing loss can make a world of difference!

Frequency Therapeutics’ FX-322: A Potential Hearing Loss Treatment on the Horizon

For as long as people have experienced hearing loss, they’ve been anxious for better treatments. And although that has remained elusive thus far, for certain types of hearing loss, a significant treatment may be coming before 2030: FX-322, the lead drug candidate from Massachusetts-based biotechnology company Frequency Therapeutics.

I recently spoke with Carl LeBel, PhD, Frequency’s Chief Development Officer, about the company, FX-322 and the potential of regenerative medicine to treat hearing loss (thanks to Suzanne Day, Associate Director of Digital and Corporate Communications, for her assistance). “We think within this decade, hopefully there’s the first hearing restoration therapeutic that’s available,” Mr. LeBel said.

FX-322 and the Formation of Frequency Therapeutics

To understand this potential treatment, it helps to understand the discoveries that lead to the formation of the company. In 2014, the company was founded based on scientific breakthroughs by Jeff Karp, PhD, Professor of Medicine at Brigham and Women’s Hospital, and Bob Langer, ScD, Institute Professor at Massachusetts Institute of Technology (MIT).

The researchers found that some body tissues regenerate much better than others. They studied the lining of the small intestine, which turns over roughly every four days, because it’s designed to absorb and distribute nutrients to other parts of the body. Drs. Karp and Langer saw the molecular pathways that signal the lining’s cells to turn over quickly and form new tissues.

Around the same time, another scientific group found very similar cells in the cochlea – but with one big difference: in the cochlea, these cells weren’t active. They saw that the cochlea’s cells didn’t regenerate and form new sensory hair cells. “So that was the formation of Frequency,” LeBel explains. “And Frequency was asking, why is that the case? Why is it that the cochlea isn’t regenerating cells and the small intestine is?”

This led to the discovery of two small molecules that make up FX-322, which targets these cells, called progenitor cells. Essentially, this process is meant to drive hair cell regeneration: The drug targets pathways to those cochlear cells, and when activated, they divide and form a new cell of themselves, called daughter cells. “And then most importantly, they form a new sensory hair cell,” LeBel says.

Six years after it was founded, the company now has a staff of close to 70 people. FX-322 has cleared phase 1/2 of clinical trials and is now in phase 2a. “That’s sort of the middle phase of clinical development where you’re really trying to characterize the efficacy of your drug,” LeBel explains.

Dr. Carl LeBel, Chief Development Officer, Frequency Therapeutics

FX-322 Findings So Far

As the company has progressed through clinical trials, they’ve made some interesting discoveries. The participants in the trials have been people with mild to moderately-severe hearing loss. And while FX-322 has a favorable safety profile for all participants, the hearing improvement was seen mostly in the moderate to moderately-severe individuals, as measured by improved word recognition. LeBel speculates that this is because people with more hearing loss have more to gain.

In a separate study, Frequency has found that delivering FX-322 directly into the ear by intratympanic injection effectively reaches the site of action in the cochlea – so it’s going right to the place where it’s needed. The drug candidate can be administered by an ear, nose throat doctor (ENT) in their office. “But importantly, you also don’t have to worry about any systemic side effects that oftentimes are challenging for other drugs, like if somebody’s taking a pill,” LeBel adds.

And in more promising news, individuals who were given FX-322 in 2018 were retested 1-2 years later, and many of them maintained their hearing improvements – which suggests that hearing function is maintained. “And that’s exactly what you want to see when you’re developing drugs to treat a chronic condition,” says LeBel.

Who Might FX-322 Help?

FX-322 is designed to treat what’s referred to as acquired sensorineural hearing loss, which includes forms such as:

  • Noise-induced hearing loss
  • Sudden sensorineural hearing loss
  • Age-related hearing loss
  • Ototoxic drug exposure

“All of those forms are associated primarily with a loss of sensory hair cells,” LeBel says. “So we think they can possibly be good candidates for FX-322.”

It should be noted that this likely excludes genetic forms of hearing loss.

Rather than being a full-on cure for all degrees of acquired hearing loss, LeBel says that Frequency sees FX-322 as “a disease-modifying drug,” meaning it may modify hearing loss. “The way we think possibly FX-322 could fit into the hearing-health world is, you could imagine there might be individuals that would be candidates for cochlear implants – you could treat them with FX-322, and it’s possible that you could take them from being a cochlear implant candidate to a hearing aid candidate,” LeBel says. Similarly, people with less severe hearing loss who are hearing aid candidates might not need hearing aids if the drug treatment is successful.

What Frequency Wants Individuals With Hearing Loss to Know

LeBel acknowledges that Frequency is treading completely new territory, and when FX-322 hopefully gets to the market in the coming years, it’s going to take a shift from all of those who deal with hearing loss – either personally or professionally – to integrate the product into the world. That means partnering with patient volunteers, patient advocates, audiologists and otolaryngologists. “All of those groups have to come together and work together for this to be successful. So we just want to tell everybody we want to be part of that partnership,” says LeBel. “We want to do whatever we can to build it and move it forward and support it. And we’re going to be successful if we do it together.”

Want to learn more about Frequency Therapeutics?

Hearing Health Foundation: Advancing the Search for Hearing Loss Cures

Funding cutting-edge researchers, the potential of hair cell regeneration, and the urgent need for a hearing loss cure: I’m excited to share exclusive excerpts from a Q&A I conducted with Timothy Higdon, the President and CEO of Hearing Health Foundation (HHF). HHF is the largest non-profit funder of scientific research in the U.S. dedicated to finding cures for hearing loss, tinnitus, and related conditions. Special thanks to Lauren McGrath, HHF’s Director of Marketing & Communications, for her assistance.

What is Hearing Health Foundation?

HHF was founded in 1958 as the Deafness Research Foundation by Collette Ramsey Baker, whose hearing was restored by surgery. In gratitude for her ability to hear, she founded the organization to develop better treatments and cures for hearing and balance conditions.

HHF has two signature research programs that work in tandem to advance hearing health. The Emerging Research Grants program, established with its founding, identifies and awards funds to innovative, cutting-edge hearing scientists who work to influence better treatments for hearing and balance disorders including tinnitus, hyperacusis, auditory processing disorders, Meniere’s disease, and Usher syndrome.

The second program, the Hearing Restoration Project, was founded in 2011 and is an international consortium of top researchers dedicated to finding cure(s) for hearing loss and tinnitus. HRP scientists work to understand how to regenerate dead or inactive inner ear hair cells in animals with the ultimate aim of replicating this process to restore hearing in humans.

Both programs are overseen by senior scientific advisory bodies comprised of hearing and balance experts based at leading research universities and academic medical centers nationwide. They are accountable to HHF’s Board of Directors, and include scientists, clinicians, and laypeople with personal connections to hearing and balance conditions.

What kind of hearing research is HHF funding now?

HHF’s focus has always been and remains funding the basic science that propels scientific knowledge forward and comprises the building blocks in the development of new treatments, devices, and approaches. Basic science research is foundational and critical to finding cures for hearing loss.

Work on restoring hearing via gene therapy is promising, and certainly inspires interest and excitement in the broader public. HRP-funded projects are working toward identifying the most promising gene mechanism to regrow human inner ear hair cells. Hopefully, this will restore hearing in many people with hearing loss and likely address other hearing-related disorders, such as tinnitus.

ERG-funded projects run the gamut of hearing and balance disorders, since advances in any one area of otology may contribute to advances in another, given the shared biological system in which all these investigators work. Funding early-career researchers, the next generation of scientific leaders, is critically important. The ERG program funds not only innovative projects but also promising researchers who are demonstrating, often early in their careers, the potential to make crucial discoveries and advances in the coming years and decades.

How does HHF see a cure for hearing loss being realized?

HHF expects that a potential cure for hearing loss may be realized through hair cell regeneration. Many instances of hearing loss are sensorineural: caused by the death of sensory cells (hair cells) of the inner ear. Most animals—including birds, frogs, and fish—are capable of regenerating their hair cells after these cells have died. However, mammals—including humans—cannot regenerate hair cells in the cochlea (hearing organ) of their inner ears, making sensorineural hearing loss in humans permanent.

HHF’s researchers do not have a projected timeline for when hair cell regeneration will be ready for clinical trials in humans. Until they reach that stage, HHF is optimistic that many other, significant findings will continue to arise through basic science research, through which many unanticipated discoveries often emerge.

Federal funding support for hearing loss research in the U.S. is low relative to its disease burden and continues to decrease. Additional funding for the Hearing Restoration Project, which is solely focused on this line of research, and the Emerging Research Grants program, which also funds some scientists working on gene therapy and hair cell regeneration issues, will expedite this process.

Why is hearing research not better funded, given the prevalence of hearing loss?

Hearing loss is a great disability, but not a direct cause of death, meaning that more serious health conditions tend to receive more funding. However, hearing loss does present with many comorbidities, like dementia, falls, loneliness, isolation, and depression, which can contribute to early mortality. Further, hearing loss remains in society a “hidden” disability, and hearing aids still widely stigmatized (80 percent of those who could benefit from a hearing aid do not wear one, according to Stanford), meaning that it remains overlooked by funders and policymakers.

What should the consumer do when faced with the question of who to donate money to?

Consumers are strongly encouraged to consider an organization’s financial efficiency, accountability, and transparency before making a charitable contribution. Charity watchdogs like the Better Business Bureau – Wise Giving Alliance, Guidestar, Charity Navigator, and Charity Watch publish impartial nonprofit evaluations to help donors make informed giving decisions. HHF is proud to maintain top rankings from each of these watchdogs as well as having been named as one of Consumer Reports’ annual “Best Charities for Your Money” list for four consecutive years. Every dollar raised is spent efficiently. Through the generosity of HHF’s board, the organization is able to fund vital research without overhead costs to donors.

What take-aways would HHF like to convey to readers?

  • Protect your hearing, because hearing loss is likely to affect you. Sensorineural hearing loss, which occurs when sensory (hair) cells in the inner ear are damaged, is permanent. Preserve your hearing. Hearing loss caused by noise is fully preventable. According to the CDC, hearing loss is the third most common chronic physical condition in the U.S. and is more prevalent than diabetes or cancer. About 48 million people in the U.S., or 15 percent, have hearing loss in one or both ears.
  • Cures are urgently needed, and additional financial support will bring us closer to them. A permanent medical solution to hearing loss will drastically improve the lives of hundreds of millions of people and will protect them from the dangers of untreated or undertreated hearing loss, including cognitive decline, falls, loneliness, and depression. 

Want to get more involved with HHF?