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.

Frequency’s FX-322 is discontinued…now what?

I’m a bit behind on sharing this, but just learned that in February, Frequency Therapeutics discontinued their FX-322 program, which had been the company’s flagship offering, and an exciting promise in the quest to cure hearing loss. Frequency also announced they would reduce their headcount by 55 percent, and instead shift their focus to clinical trials of a multiple sclerosis program.

This is a stark change from 4 months prior, when the company was in the midst of a phase 2b study and hoping to achieve Breakthrough Therapy designation from the FDA.

The FX-322 journey was long and cautious. Frequency started phase 1/2 clinical trials back in 2019. Over the years, they were able to show that the drug was safe, and that some participants were able to make gains in their high-frequency hearing threshold and word recognition scores.

However, as the pool of participants in clinical trials increased, FX-322 and FX-345—the next iteration of the drug that went further into the cochlea—failed to show statistically meaningful improvements, according to a press release on Feb. 13.

But according to Cliff Olson, AuD, “this [FX-322] was always going to be a long shot.” There isn’t going to be a hearing restoration drug on the market anytime soon.

For people with hearing loss, this news is incredibly disappointing. Of course, we’re used to disappointment; we live with hearing loss, after all. But it can feel even more frustrating to see the lack of progress when there are breakthroughs in treating other chronic health conditions all the time now.

The only thing I can say, based on the incredibly talented researchers I’ve been able to interview for this blog, is that the path to scientific progress is rarely a straight line. It’s a long process of experimentation. When something doesn’t work, it does help point the way to what may work in the future—but how far in the future is still a mystery.

Thanks to all the researchers at Frequency Therapeutics for their efforts over the years. They are still much appreciated.

Progress and Promise With Frequency Therapeutic’s FX-322 to Treat Acquired Hearing Loss

Frequency Therapeutics is making even more progress with their development of FX-322, a drug candidate in clinical trials to potentially restore acquired sensorineural hearing loss. The company has now completed enrollment of its phase 2b study of the drug candidate, and plans to release study data in the first quarter of 2023.

The large phase 2b study is designed to look at efficacy and safety, and includes a broad number of secondary outcome measures. “The study is powered to detect a statistically significant (p<0.05) difference between FX-322 and placebo subject groups,” Carl LeBel, PhD, Frequency’s Chief Development Officer. P<0.05 means there is less than a 5 percent chance that the changes aren’t real. If this study goes well, the next step is phase 3 trials. “Assuming we have positive data, we would meet again with the FDA and file for Breakthrough Therapy designation,” says Dr. LeBel. Breakthrough Therapy designation is designed to expedite the development and review of drugs that demonstrate substantial improvement over existing therapies. Of course, there are currently no drug therapies available to improve hearing loss, so this would be the first of its kind.

More Participants, More Hearing Gains

The phase 2b study has enrolled 142 individuals at 28 different clinical sites throughout the U.S. The participants are adults between 18-65 years old who have either noise-induced or permanent idiopathic sudden hearing loss, which are considered “acquired” hearing loss. “Our study population are people who’ve had a cochlea that was working well, that stops working well because of some force on it, such as noise or other external factors,” says Kevin Franck, PhD, Senior Vice President of Strategic Marketing and New Product Planning.

Due to what the company has learned from previous trials, the study population is also comprised of people with higher mild to lower severe hearing loss range, as they seem to respond best to the drug candidate. Improvement response is focused on better speech perception. With improved speech perception, individuals may hear words more clearly, a critical unmet need for individuals with hearing loss.

Measuring Improvement of FX-322

First, the study group is divided into people who will get a placebo, and those who will get FX-322. FX-322 participants get a single injection of the drug in their middle ear. Ninety days after, they undergo a speech perception test, which people with hearing loss do routinely when they are examined by an audiologist. A list of 50 words is read out loud, and the person has to repeat them back.

Although a 10 percent improvement is considered clinically meaningful, Frequency is also looking for what is statistically significant. So, while an extra 5 correct words would be a 10 percent improvement, “Some of the differences we’re seeing are actually twenty words out of fifty,” which is quadruple that, says Dr. Franck. To be deemed successful, a statistically significant (p<0.05) percent more of the participants treated with FX-322 have to show clear improvements in their speech perception compared to the placebo group.

The drug also seems to be well-tolerated in participants. “The beauty of doing local delivery to the ear is you don’t have to worry about systemic side effects,” says LeBel. The drug gets straight into the cochlea, and while people who receive it may feel a sense of fullness in their ear, the discomfort is mild and temporary, with no lasting side effects observed. “That’s really important for therapy of this nature,” LeBel adds.

Looking to the Future

The team has learned a lot from their previous trials of the drug, and the possibility that FX-322 will be available on the market in the not-too-distant future draws closer. “We feel confident that we’ve designed a study in the best way possible to be able to demonstrate very clearly that FX-322 can provide a benefit in hearing loss,” says LeBel. “We really can’t wait to see the results.”

More to come in early 2023 when the study results are published.

Frequency Therapeutics: Strides Towards a Disease-Modifying Therapy for Acquired Hearing Loss

Last year was a busy and eventful one for Frequency Therapeutics, the Boston-based biotech company working on FX-322, a drug candidate in clinical trials to potentially restore sensorineural hearing loss. The company has learned some interesting lessons from clinical trials of FX-322 conducted in 2021, and has also introduced a new clinical candidate, FX-345, that they hope will be able to get even deeper into the cochlea – potentially enabling treatment of different populations of patients with acquired hearing loss.

So far, Frequency has run 4 clinical trials of FX-322 in phase 1, which is the first step towards developing a drug approved by the Food and Drug Administration (FDA) to be used to treat a given condition. In phase 1, researchers test for drug safety and the maximum effective dose of a drug in humans. The company has run 5 trials to date and has just begun their largest, a new phase 2b study.

Results of Previous FX-322 Clinical Trials

Frequency has thus far found in three separate studies that hearing improvements can be seen following a single administration of FX-322, when testing participants’ hearing 90 days following dosing to see if their speech perception measures increased. These participants had hearing loss ranging from mild to severe. “Speech perception is important because that’s what people with hearing loss have told us is the critical unmet need. They said, ‘We struggle to hear conversations, particularly in noise,'” says Kevin Franck, PhD, Senior Vice President of Strategic Marketing and New Product Planning.

When tested, some participants showed an increase in word recognition – in a test of 50 words, the highest was an increase of 20 words, or a 40 percent increase in the words recognized. The drug was well-tolerated in people. And in a separate study, the company re-tested the hearing of participants who had received the drug a year or two prior. “Some of those people continued to have that benefit [of increased word recognition], which makes sense, because we believe we’re restoring some of the original biology – and that original keeps working,” Dr. Franck adds.

A Game-Changing Possibility

These results represent potentially a huge advance in the field of hearing restoration. “This is suggesting that the drug could be disease-modifying – so you’re actually correcting the underlying condition,” says Carl LeBel, PhD, Frequency’s Chief Development Officer. “And we can’t think of a single example where you’ve given one dose of an agent, you produce an effect, and that effect lasts for this long.”

So far, the company has had the most success in treating people who have sudden sensorineural hearing loss with no known cause (meaning not caused by trauma or another obvious factor), as well as people with noise-induced hearing loss. Together, these fall into the category of acquired adult sensorineural hearing loss. “Where we have the most confidence about the percentage of responses is in moderate to moderate- severe range due to noise and sudden hearing loss,” Franck says. “And that’s the group that we’re using to study this next clinical trial that’s underway.”

This isn’t to say that the company is ignoring other hearing loss populations, such as those with age-related hearing loss, or those who are given drugs that diminish hearing, such as certain cancer patients. “We’re going to continue to study them,” says Dr. LeBel. “But for us to get the drug approved as quickly as possible, we want to focus in on the populations that have shown the greatest response so far.”

How to Learn More about Frequency’s Current Clinical Trial

Frequency’s current clinical trial is a double-blind, placebo-controlled phase 2b study, in which researchers are studying the drug candidate with a larger group of patients to assess effectiveness and further study safety. The company has expanded testing to 27 different sites around the country. To qualify, you need to have noise-induced hearing loss or sudden hearing loss and be between 18 and 65 years old. To see if there is a testing site near you, visit the study’s page. There is also a separate website with a questionnaire to see if you qualify for the study.

FX-345: Another Clinical Trial to Come

The company is also working on a new clinical candidate for hearing restoration, called FX-345, which is designed to go further into the cochlea to potentially activate more progenitors to restore hearing function. FX-345, like FX-322, is a combination of two drugs that Frequency believes are required to activate cells in the cochlea to divide and then form new hair cells. “What we have done is taken one of those drugs, and we’ve swapped in a new drug that goes after the same target, but that new drug is much more potent than the one that’s currently in FX-322,” LeBel says.

Because of the activity of the drug and its concentration, researchers believe that they may be able to restore some of the lower frequencies in the cochlea, not just the high frequencies that are on the outer part. “So the might open up the door that some of the folks that aren’t responding to FX-322 for whatever reason,” LeBel adds. Clinical trials for FX-345 are expected to start in the second half of 2022.

For more information on the current FX-322 trial, check out, or visit Frequency Therapeutics.

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 Ramps Up as FX-322 Trials Continue

Big things are happening at Frequency Therapeutics, the company with drug FX-322 in clinical trials to potentially restore sensorineural hearing loss.

Today, the company welcomed Kevin Franck, PhD, as Senior Vice President of Strategic Marketing and New Product Planning. Dr. Franck will be leading pre-commercial strategy and launch planning for
Frequency’s clinical pipeline, including FX-322.

Franck joins Frequency from Massachusetts Eye and Ear in Boston, a Harvard University teaching hospital that focuses on eye and ear care and research, where he was Director of Audiology. Prior to that, he was Head of Marketing for Bose Hear, a division of Bose Corporation, where he led new product management and channel marketing of an emerging category of business focused on hearing loss.

Franck’s addition to Frequency comes at an important time for the company, as they will be sharing phase 2A data of clinical trials for FX-322. “I’m excited to join Frequency at this important time and contribute to advancing the field toward hearing regeneration,” said Franck in a press release. “Currently available hearing devices have been an incomplete solution and many patients continue to struggle to understand speech and with sound clarity. Repairing the underlying damage that is the primary cause of acquired hearing loss has always been the ultimate objective, and Frequency may be on the cusp of addressing this ambitious goal.”

Sounds (pun intended) promising!

Decibel Therapeutics: Pivoting to Gene Therapy Treatment for Hearing Loss

Decibel Therapeutics, a Boston-based biotechnology company, announced last week that they have raised $82 million to pursue gene therapies for hearing loss. This is exciting for a few reasons:

  1. Genetics is one of the leading causes of hearing loss. According to the CDC, 50-60 percent of children born with hearing loss have it due to genetics. And genetic causes of hearing loss tend to be more severe, meaning they impact a person even more than milder forms of hearing loss.
  2. Other treatments in the works, such as Frequency’s FX-322, target other causes of hearing loss, but not genetics. So Decibel’s work has the potential to help an entirely different population of people.

Interestingly, Decibel was previously working on treatments that would help prevent hearing loss from happening in the first place. But according to Endpoint News, due to recent advances in genomic and regenerative technology, the company decided to shift to gene therapy for people who already live with hearing loss.

Currently, Decibel’s gene therapy program aims to test children with genetic deafness due to the otoferlin gene (OTOF). OTOF is one of the most frequent causes of sensorineural hearing loss. According to a May 2019 study published in PLos One, more than 160 mutations in OTOF have been identified so far. It tends to cause severe to profound hearing loss in children from birth. The idea is that the company’s technology will help to focus on the deficient hair cells in the ear and restore them.

Decibel’s long-term goal is to create cures for other genetic causes of hearing loss once the OTOF program is successful. That is currently in preclinical stages, and the company expects to start clinical testing in 2022, according to their press release.

Update on Frequency’s FX-322: Expanding Test Groups to Include Severe Hearing Loss and Age-Related Hearing Loss

As I wrote recently, Frequency Therapeutics’ drug candidate FX-322 is shaping up to potentially be the first biopharmaceutical treatment for hearing loss on the market some time in the next decade.

Now here’s an update: The company is currently in phase 2a of clinical trials, and they announced last week that they will report a 90-day analysis of the phase 2a study of FX-322 by late Q1 2021, according to their Associate Director of Digital and Corporate Communication, Suzanne Day.

While the promise of new data is already exciting news for those with hearing loss, there’s more to share: Frequency is expanding the potential reach of FX-322 to include two important groups. New studies have begun in patients with age-related hearing loss (ages 66 – 85) and those with severe sensorineural hearing loss. These studies will provide data on the potential of FX-322 for a far broader group of patients.

Severe Hearing Loss Group

According to a 2016 study published in the American Journal of Public Health, an estimated 6.6 million Americans (2.5 percent) of Americans 12 years and older have severe to profound hearing loss. As the description implies, this degree of hearing loss has a severe impact on a person’s quality of life. The Hearing Health Foundation states that without hearing aids or cochlear implants, speech isn’t understandable for those with a severe hearing loss. If anyone is in need of a hearing breakthrough, it’s this group!

“The severe population study will include patients with more dramatic loss in hearing function, and likely no functional hearing in certain parts of cochlea,” says Carl LeBel, PhD, Frequency’s Chief Development Officer. This group will likely include patients whose hearing loss results from a range of causes (noise-induced, sudden hearing loss, and ototoxic, for example). “Since all of these causes are associated with a loss of sensory hair cells, we are interested in evaluating how these subjects compare to less severe subjects in their response to FX-322,” Dr. LeBel says.

Age-Related Hearing Loss Group

The National Institute on Deafness and Other Communication Disorders states that approximately one in three people in the United States between the ages of 65 and 74 has hearing loss, and nearly half of those older than 75 have difficulty hearing. There were over 54 million people aged 65 and over in 2019, according to the U.S. Census  Bureau. Needless to say, the age-related hearing loss group is quite large. So the potential for FX-322 to help them in their golden years is profound (pun intended!).

Although Frequency’s test group includes people who are between 66 and 85 years old, “This type of hearing loss is acquired and gradually worsens over time, and can begin as early as a person’s 30s or 40s,” LeBel says. “It is often thought of as resulting from a chronic low-grade exposure to noise over a lifetime, and not just as a result of aging.”

Signing Up for a Trial

If you or someone you know fits into one of these categories and is interested in participating in a clinical trial, check out this link for the age-related study. There are multiple testing sites across the United States. The severe hearing loss study has not yet begun, but you can keep an eye on for when this opens up.

More updates to come as they are available!

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?

Hough Ear Institute: Small But Mighty

Last month, I had the good fortune to interview Rick Kopke, MD, FACS, the CEO of the Hough Ear Institute (HEI) in Oklahoma City, Oklahoma. HEI, or Hough for short, is a non-profit 501(c)(3) organization with the vision that “all who have ears will hear.” Hough’s mission is three-pronged: hearing restoration research, education (training otolaryngologists), and humanitarian efforts to send doctors to underdeveloped countries to perform ear surgeries. “We’re a small but mighty organization,” Dr. Kopke says. “By God’s grace, we’ve come up with some real breakthroughs.”

The Hearing Loss Pill

The most recent breakthrough is the advancement of a hearing loss pill, which is moving from phase 1 to phase 2 of clinical trials to test for safety and efficacy. An agreement between HEI’s pharmaceutical partner, Auditus LLC (Auditus), a wholly owned subsidiary of Otologic Pharmaceutics Inc. (OPI), and Oblato Inc. (Oblato) made the move possible. “The hearing loss pill was originally designed for use in the military,” Kopke explains. “It was designed to be taken shortly after an explosion, being in a fire fight, or other loud noise to reduce permanent hearing loss.” But HEI’s researchers found an interesting surprise: the nerve endings between the auditory nerve and the inner hair cells, called the synapses, can be regenerated with the pill too. That means it may also help treat tinnitus, the incessant ringing in the ears that plagues many people with hearing loss. 

Although the hearing loss pill was originally developed for noise-induced hearing loss, Kopke says it could also help other groups: those with age-related hearing loss; those who receive antibiotics or other medications that can be toxic to the ear; and cochlear implant recipients, by helping to preserve more of their natural hearing after cochlear implant surgery. “The pill could also improve ability to hear speech in noise – restoring nerve fibers helps to restore hearing,” says Kopke.

Other projects Hough is working on include regeneration of auditory hair cells to restore hearing through gene therapy (a regenerative injection technology), and a new way to deliver drugs to the inner ear. They aren’t pursuing other projects at this point due to the organization’s size. “If you have too many things going on, if you lose your focus, then you stop making progress,” Kopke says.

What Will Future Treatments for Hearing Loss Look Like?

Because there are different types of hearing loss, Kopke anticipates that there will be different treatments in the future – and these might not entail a full restoration of hearing in more severe cases. “There won’t be a silver bullet, a drug that restores all types of hearing loss,” he says. “The causes of hearing loss are so varied and the pathology that underlies sensorineural hearing loss is so varied that there’s not going to be one medication that’s effective in all cases.”

Rather, Kopke thinks the hearing loss pill and other treatments will offer significant partial restoration of hearing. For example, a person with mild hearing loss who would wear hearing aids could receive a regenerative medicine and might not need hearing aids, or someone who might need a cochlear implant could get medicine and might go to using hearing aids. Or for others, they might still need to use hearing aids or cochlear implants, but with the medication, their devices would work much better. “So, I think there will still be hearing aids and cochlear implants, but I think there will be a lot of people who benefit very significantly from these medications if we can take them through phase three of clinical trials,” Kopke says. After phase three, a drug can be approved by the FDA to go on the market.

While this may sound discouraging to people with hearing loss who are hoping to have their hearing fully restored, it’s actually good news that this type of advancement doesn’t seem as far off as before. “I really think the prospects are very good. I’m quite hopeful that our technology, or some of the technology others are working on, will work out and get all the way through phase three.” Kopke says when he started working in the hearing field in the late 1990s, technology companies had almost no interest in funding pharmacological treatments for hearing loss. “But there are now clinical trials and many pharma companies are interested,” he says. “I still think we’re going to get some winners here. It seems like the pace is increasing.”

What Can You Do to Speed Up Development of a Treatment for Hearing Loss?

If you are looking to donate to an organization that is working on hearing restoration research, Kopke says there are many to choose from. “People should take time to do their homework. There are great organizations to donate to,” Kopke says. “See if the organization has a track record of making discoveries and making progress, and don’t feel shy about contacting people before you donate.” Rather than focus on one organization, Kopke says it may be best to spread the wealth when donating. “I think it’s good to support the research broadly, because you don’t know which drugs are going to make it [to market].”  

In addition, it’s important to keep your expectations realistic – if you donate today, a treatment for hearing loss isn’t going to be ready by tomorrow. “Research takes so much time,” he says. “Certainly, with more funding you can speed things up, but it just takes time.”

Kopke says that a major benefit of donations is that they help to keep research going over the long term, which isn’t a guarantee with government funding. HEI has Department of Defense (DoD) funding and has had National Institutes of Health (NIH) grants, as well as OCAST grants from the state of Oklahoma, but “the allocation for research money for DoD and NIH and other granting agencies goes up and down. After a few years, even if you’re doing tremendous work, those monies can dry out. That’s where consistent donors can help keep research moving forward and on track.”

Sometimes it can be hard for donors to give money to an organization when they don’t know what specifically it’s going towards. “Some people like to give to a particular project, or for equipment,” he notes. Currently, Hough is looking for funding for a few different projects: an advanced proof-of-study concept for tinnitus; and to look into tau protein, which causes the nerve cells in the auditory pathway to degenerate over time. And on the equipment side, they need funding for a special freeze-dryer system to help with reliable synthesis of nanoparticles used for inner ear drug delivery. 

Other Ways to Speed Up Development of a Treatment for Hearing Loss

It’s also important for people with hearing loss to share their stories, as people with full hearing often don’t know how much a person can struggle with hearing loss and how much it can affect relationships, education, and work. “We realize that if we help restore hearing we can help restore or improve relationships,” says Kopke. “We are created to thrive in relationships with one another, and sometimes hearing loss can really impair relationships.”

You can also let legislators know, either at the state level or federal level, that you think hearing loss is an important condition that deserves attention and funding. 

Donating to Hough Ear Institute

HEI wants to thank donors for being able to reach the breakthroughs they’ve accomplished, like the hearing loss pill. “We are extremely grateful for the support we’ve had over the years,” Kopke says. “We’ve had donors from all over, and we want to thank people who’ve made our work possible.” 

Hough is now focused on the future and hopefully getting the hearing loss pill through phases two and three. “We are very efficient in the way we use our research dollars and try to stretch them as much as we can,” Kopke says. At the end of the day, the staff at Hough has tremendous motivation to help the hearing loss community. “All our researchers are really driven by passion to help people,” Kopke says. “We love what we’re doing.”To keep that work going, you can donate to Hough Ear Institute, and if you’d like your donation to go to a specific cause, note that in the comments.

The Speed of Science

We live in a world that likes simple, straightforward answers.

“Who won the [insert any sport here] game?”

–“This team won, and the other team lost.”

But the more complex the question, the harder this type of zero-sum response can be.

And when it comes to the question of “When will there be a cure for hearing loss?,” at this point, there’s no easy answer—which doesn’t really square away with our desire for clickbait-worthy headlines (“Scientists CURE DEAFNESS!”) and assertions that are 140 characters or less, including hashtags (“Did you go to too many rock concerts? Now hear this! #hearinglosscure”).

To understand why a cure for hearing loss has been elusive so far, it helps to understand the scientific process. “Science moves incrementally at some level, but the reality is, leaps happen randomly,” says Dr. Tony Ricci, one of the principal investigators (P.I.’s) at the Stanford Initiative to Cure Hearing Loss (SICHL) and professor in the School of Medicine and professor, by courtesy, of molecular and cellular physiology at Stanford University. At SICHL, researchers are looking at multiple approaches to cure different forms of hearing loss, including through regeneration, stem cell therapy, and gene therapy. “So some of these have timelines of a year or two, and some of these have timelines of 10 years,” says Dr. Ricci. “And some of them we try not think about what the timeline is, because you don’t know.”

This can be hard for journalists to write up, since “We don’t know when” doesn’t make a great headline – even if it is the truth.

Science also requires a willingness to experiment, and qualified people to conduct these experiments. Ricci likens the progress of a hearing loss cure to the search for an effective treatment for HIV and AIDS over the past few decades. There wasn’t one researcher with a lot of money who found the answer. Rather, “It was now you had 1,000 people all trying to answer the question,” Ricci explains. “So there were 1,000 shots and there were a couple of hits, and so it moved forward.”

But the caveat is that there aren’t nearly as many people working in the field of hearing research as there were on HIV, partly because hearing loss isn’t fatal. But it’s also because the ear – specifically the cochlea, which, along with the brain, is responsible for hearing – is a difficult body part for researchers to access. “Hearing doesn’t move forward at the same rate as say vision research, because there’s 10 percent of the people doing it,” Ricci says. “You can count on my hands the number of labs that do the experiments that I do in the world, not in the United States.”

Science is also dependent on, well, scientists. Unlike being a brief sensation on Tik Tok, becoming a scientist in the hearing field isn’t something just anyone can do. Regarding himself and his fellow P.I.’s, Ricci says, “To be successful in science, you need really broad training, broader training that what any of us had way back when we were at school. I think this is specifically true in the hearing field.” This also means finding and recruiting the next generation of scientists, a process in itself.

I had thought that a cure for hearing loss was simply about money – and while things are always at least a little bit about money, it goes far beyond that. While we wait for the leap to a cure, the scientific process is actively happening – perhaps without fanfare, but no less important to the overall goal.

You can help accelerate the progress of SICHL by becoming a donor. For information, email Dr. Cliff Harris at

The Stanford Initiative to Cure Hearing Loss: Groundbreaking Work in a Too-Neglected Field

Today is World Hearing Day, an annual global initiative from the World Health Organization to promote hearing care and raise awareness of hearing loss. In honor of this day, I’m going to spotlight an organization doing amazing work in the field of hearing research: The Stanford Initiative to Cure Hearing Loss (SICHL).

I was lucky enough to go to the Stanford campus a few weeks ago to meet with three of the researchers – known as principal investigators (P.I.’s) – and the development director of SICHL. I gleaned so much great information that I’ll be writing a SICHL series. For now, I’d start by introducing the organization and their mission.

SICHL was founded 14 years ago by Dr. Robert Jackler, department chair, and Dr. Stefan Heller, a research professor in the otolaryngology department at Stanford University School of Medicine. Dr. Heller’s research career has focused on finding a cure for deafness.

In 2006, when asked in a development meeting if there was anything that would help his research, Dr. Heller said, “Well, if someone could give us 200 million dollars, we could cure deafness in 10 years.” This led to the formation of SICHL and the recruitment of additional inner ear researchers. There are currently six P.I.’s in SICHL who each have their own lab with post-doctoral students who help conduct their studies, as well as the development director who handles fundraising.

One of the unique aspects of SICHL is that each P.I. has an area of specialty – and together, they can make faster progress on their studies because of this. Of the three P.I.’s I interviewed, Dr. Heller’s expertise is in stem cells, Dr. Nico Grillet’s is in genetics, and Dr. Tony Ricci’s is in electrophysiology. “We have experts in different aspects of this [hearing] research,” said Grillet. “And I don’t see any other center that has this.”

The SICHL labs, in one of the Stanford School of Medicine buildings, are situated in a way that fosters collaboration as well. “There’s a rare co-location here, which is very unusual at an academic medical center,” says Dr. Cliff Harris, SICHL’s development director. “There’s a department of physics and engineering, chemistry, and biology, and they are within 100 yards of where we are in the medical school.”

Recruiting qualified Stanford students to help in the P.I.’s labs is core to the success of the organization. “Training the next generation of scientists to be better than us is really important,” says Ricci. “And having resources to put into that is also really important.”

The SICHL researchers have multi-pronged approaches to examining hearing loss. This includes trying to understand how animals, such as birds, can re-grow their damaged inner ear cells, something humans cannot do; seeking ways to stimulate mammalian hair cells to regenerate, currently being done in mice; inventing immensely powerful microscopes to take incredibly detailed photos of hair cells and even watch hair cells in action transmitting sound in a live animal, in order to understand how genetic mutations cause hearing loss; using sophisticated computer modelling to design new experiments that will reveal the intricate functioning of the cochlea; studying fish with transparent brains to peer into the inner ear of animals with similar genetic hearing loss mutations to humans; and devising ways to avoid the hearing loss caused by toxic medications such as chemotherapy and certain antibiotics.

To conduct these experiments takes money – and donations of all sizes are greatly appreciated. Also, larger donations are fantastic because the team can leverage those funds across the various SICHL labs to make collaborative, transformational advances. You can donate to SICHL or learn more about their mission. Or for more details about how your gift can make a difference, email Dr. Cliff Harris at

In my next blog post, I’ll be delving deeper into the science of hearing research – and why despite the headlines, a cure probably isn’t just around the corner (but there’s still a lot of exciting stuff happening!).

Welcome to

Hearing loss affects millions of people — so why doesn’t it get more attention? And why isn’t it taken more seriously? Why are treatment advances so slow?

We’re looking to change that, by showing what it’s really like to be living every day with a challenge that affects virtually every facet of life.

Gene Therapy to Cure Hearing Loss: Sooner Than We Think?

For years, we’ve heard that gene therapy could one day offer a cure for hearing loss. And while that day is still not here, it may also not be as far off as some people think.

I recently heard updates from some of the researchers at the Stanford Initiative to Cure Hearing Loss (SICHL), detailing where they are in their current work and what they anticipate for the future. One update came from Teresa Nicolson, PhD, head of the Nicolson Research Lab at SICHL.

Dr. Nicolson discussed the fact that there is already a gene therapy on the market to treat a form of blindness: Luxturna, which is used to treat patients with inherited retinal disease due to mutations in both copies of the RPE65 gene. It was approved by the FDA in 2017. “I think we’re entering into a rapidly expanding translational phase for gene therapy,” she said to me in an email.

Luxturna is just one of six gene therapies that have been recently approved. The others are for muscle degeneration and immune disorders.

“There currently is an antisense oligo therapy in clinical trials for Usher syndrome (USH2A), which causes deaf/blindness,” Nicolson said. “The goal of the clinical trial is to restore vision, but this reagent could also be used to improve hearing loss in these Usher patients. So I think we are very near to these type of treatments!”

The Stanford researchers agree that curing hearing loss is not a matter of if, but when. As we’ve seen in the past year with the lightening-speed development of the COVID-19 vaccine, with enough money and resources, it’s possible to come up with novel treatments in an astonishingly short time.

While hearing loss doesn’t carry the same urgency as a potentially fatal condition like COVID, those of us who are personally affected know that it still has a profound impact on our lives — and that better treatments are needed.

With enough awareness, and enough money, the researchers assert that treating inner-ear hearing loss will one day be as effective as the treatments we currently have for middle ear problems (conductive hearing loss, which can be fixed).

Check out more about the work at SICHL or donate to help speed up science.