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.

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.

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.

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.