Reversing Hearing Loss With Regenerative Therapy

Summary: A new regenerative therapy uses small molecules to program progenitor cells derived from stem cells in the inner ear to grow new hair cells within the cochlear and restore hearing.

Source: MIT

Most of us know someone affected by hearing loss, but we may not fully appreciate the hardships that lack of hearing can bring. Hearing loss can lead to isolation, frustration, and a debilitating ringing in the ears known as tinnitus. It is also closely correlated with dementia.

The biotechnology company Frequency Therapeutics is seeking to reverse hearing loss—not with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hear.

Hair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency’s drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people’s hearing as measured by tests of speech perception—the ability to understand speech and recognize words.

“Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” says Frequency co-founder and Chief Scientific Officer Chris Loose Ph.D.

In Frequency’s first clinical study, the company saw statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years.

The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies, with some improvements lasting nearly two years after a single injection. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial.

Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA, Senior Vice President Will McLean Ph.D., and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the clinical trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. and hundreds of millions more around the world.

“Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.”

From the lab to patients

In 2005, Lucchino was an MBA student in the MIT Sloan School of Management and Loose was a Ph.D. candidate in chemical engineering at MIT. Langer introduced the two aspiring entrepreneurs, and they started working on what would become Semprus BioSciences, a medical device company that won the MIT $100K Entrepreneurship Competition and later sold at a deal valued at up to $80 million.

“MIT has such a wonderful environment of people interested in new ventures that come from different backgrounds, so we’re able to assemble teams of people with diverse skills quickly,” Loose says.

Eight years after playing matchmaker for Lucchino and Loose, Langer began working with Karp to study the lining of the human gut, which regenerates itself almost every day.

With MIT postdoc Xiaolei Yin, who is now a scientific advisor to Frequency, the researchers discovered that the same molecules that control the gut’s stem cells are also used by a close descendant of stem cells called progenitor cells. Like stem cells, progenitor cells can turn into more specialized cells in the body.

“Every time we make an advance, we take a step back and ask how this could be even bigger,” Karp says. “It’s easy to be incremental, but how do we take what we learned and make a massive difference?”

Progenitor cells reside in the inner ear and generate hair cells when humans are in utero, but they become dormant before birth and never again turn into more specialized cells such as the hair cells of the cochlea. Humans are born with about 15,000 hair cells in each cochlea. Such cells die over time and never regenerate.

In 2012, the research team was able to use small molecules to turn progenitor cells into thousands of hair cells in the lab. Karp says no one had ever produced such a large number of hair cells before. He still remembers looking at the results while visiting his family, including his father, who wears a hearing aid.

“I looked at them and said, ‘I think we have a breakthrough,'” Karp says. “That’s the first and only time I’ve used that phrase.”

The advance was enough for Langer to play matchmaker again and bring Loose and Lucchino into the fold to start Frequency Therapeutics.

The founders believe their approach—injecting small molecules into the inner ear to turn progenitor cells into more specialized cells—offers advantages over gene therapies, which may rely on extracting a patient’s cells, programming them in a lab, and then delivering them to the right area.

“Tissues throughout your body contain progenitor cells, so we see a huge range of applications,” Loose says. “We believe this is the future of regenerative medicine.”

Advancing regenerative medicine

Frequency’s founders have been thrilled to watch their lab work mature into an impactful drug candidate in clinical trials.

“Some of these people [in the trials] couldn’t hear for 30 years, and for the first time they said they could go into a crowded restaurant and hear what their children were saying,” Langer says. “It’s so meaningful to them. Obviously more needs to be done, but just the fact that you can help a small group of people is really impressive to me.”

Karp believes Frequency’s work will advance researchers’ ability to manipulate progenitor cells and lead to new treatments down the line.

“I wouldn’t be surprised if in 10 or 15 years, because of the resources being put into this space and the incredible science being done, we can get to the point where [reversing hearing loss] would be similar to Lasik surgery, where you’re in and out in an hour or two and you can completely restore your vision,” Karp says. “I think we’ll see the same thing for hearing loss.”

This shows hair cells and cellular regeneration within the ear
These images show cellular regeneration, in pink, in a preclinical model of sensorineural hearing loss. The control is on the left and the right has been treated. Credit: Hinton AS, Yang-Hood A, Schrader AD, Loose C, Ohlemiller KK, McLean WJ

The company is also developing a drug for multiple sclerosis (MS), a disease in which the immune system attacks the myelin in the brain and central nervous system. Progenitor cells already turn into the myelin-producing cells in the brain, but not fast enough to keep up with losses sustained by MS patients. Most MS therapies focus on suppressing the immune system rather than generating myelin.

Early versions of that drug candidate have shown dramatic increases in myelin in mouse studies. The company expects to file an investigational new drug application for MS with the FDA next year.

“When we were conceiving of this project, we meant for it to be a platform that could be broadly applicable to multiple tissues. Now we’re moving into the remyelination work, and to me it’s the tip of the iceberg in terms of what can be done by taking small molecules and controlling local biology,” Karp says.

For now, Karp is already thrilled with Frequency’s progress, which hit home the last time he was in Frequency’s office and met a speaker who shared her experience with hearing loss.

“You always hope your work will have an impact, but it can take a long time for that to happen,” Karp says. “It’s been an incredible experience working with the team to bring this forward. There are already people in the trials whose hearing has been dramatically improved and their lives have been changed. That impacts interactions with family and friends. It’s wonderful to be a part of.”

About this auditory neuroscience and genetics research news

Author: Zach Winn
Source: MIT
Contact: Zach Winn – MIT
Image: The image is credited to Hinton AS, Yang-Hood A, Schrader AD, Loose C, Ohlemiller KK, McLean WJ

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  1. Hearing loss started in the right ear, the left ear has now caught up and to some extent surpassed–Have been wearing hearing aids for about 8 years now- Just had another test and the progression continues- Would love to try anything to at least stop the loss if not reverse it-

  2. Was born with less than 10% hearing in my left ear while the right ear was perfectly normal. About five years I mysteriously experienced sudden and dramatic hearing loss in my good ear. I’ve had a hearing aid ever since and even at that I have approximately 60% hearing in my good ear while wearing the hear aid. Dr. tells me hearing aids cannot help me with the left ear which is down to approx. 3% hearing. I’m now age 60 and would be very interested in participating in this study.

  3. Lost quality hearing from measles at age 4. Hearing not clear and now worse with age. Would stem cells regenerate hair cells in cochlea due to a viral infection?

  4. I lost my left ear’s hearing when I was about 8 years old due to taking some antibiotic medications. It has been 50 years now. I also lost my right year’s hearing for about 50% about 12 years ago due to stress. It is a great news to know that there is a light at the end of the tunnel. When/How can we take the treatment?

  5. My wife had sudden hearing loss in April 2010 and has been battling tinnitus since. She has anxiety daily and developed other problems. We would be very interested in participating in your study

  6. I am very interested in participating in this study. Please let me know how to get involved. I would like to get incolved.

  7. I am very interested in participating in this study. I began having difficulty hearing in my 40’s. Please let me know how to get involved.

  8. I have hearing loss
    Where will the research be done & how much does it cost for the shot in the ear.

  9. I am active duty military overseas and our now 15 year old daughter had 85 percent hearing loss on one side after ear infection. She is an international swimmer and now had a hearing aid .. how do I find out more information for enrolling her in the study

    CAPT Kevin Buckley MC USN

  10. I had tinnitus in my rt eat it’s gone from my implant. The left ear I have 95 percent loss. Could this help me. Sign me up

  11. I would be a great candidate for the trials. Worked as a carpenter my whole adult life. To say the least if this would make me hear again would be a God send.

  12. I have hearing loss and wear bi-cross hearing aids. I would like to know more about this regenerative procedure. Thank you

  13. Hi! I am 50 years old and about to retire from the United States Navy in 2023 after serving over 23 years. I have been diagnosed with Tinnitus and considerable hearing loss. If there is a way, I am very interested in becoming a test patient for the progress of this new therapy…
    Reversing Hearing Loss With Regenerative Therapy
    Auditory ·March 29, 2022
    I currently live in Virginia Beach until I retire in September 2023 and move to Southern NH.

  14. I have nerve deafness. The auditory nerve in my left ear is not what it should be. Why does no one try to correct that problem? It is very frustrating and very isolating.

  15. I began to lose my hearing right after basic infantry training in the Marine Corps back in 1969; over the ensuing years, particularly in the last three I have lost almost all my hearing; it had changed my life indeed. I live under severe social isolation as a result, and at times. In the last few months, I seem to be starting dementia right eye ball to eyeball.
    I wonder if the research the article alludes to is, or will be available to for patients like me. That information would be God sent to me.

    Thank you,
    Louis E Aranda
    Brooklyn, NY

  16. I would love to be a candidate for restoring my hearing! This is such great news and I hope it is approved soon

  17. Just how can you be picked to be candidate for this hearing cell therapy for I’m having trouble with hearing loss

  18. As a person experiencing significant hearing loss, I read with interest this article on the use of regenerative therapy to reverse hearing loss. I am interested in taking part in any clinical trials being conducted in this regard. Please let me know how I might apply to get on the list of potential participants.

  19. I started losing my hearing at 40…with no explanation why..just called profound hearing loss…I have hearing aids but still struggle. I pray for a cure.

  20. So excited by this. I would LOVE to be a part of the study if I can. Do you know who I can contact?
    Loss of hearing completely changed my life. I have a special needs Grandaughter that I help care for and this new development could help me (and her) tremendously.

  21. Would this help ANSD deafness? If so I would be interested in my son participating in clinical trial please please!!! Pls contact me!

  22. Would this work for deaf children with ANSD?! If so, I would be interested in my son participating in clinical trail! Please contact me, he needs help hearing!

  23. I have sensorineural hearing loss both ears ,born with it now age 65, almost totally deaf ,hearing aids do not help me cannot understand anyone anymore

  24. How can I get involved in this study? I have profound hearing loss and my daughter who is nearly 11 has moderate to severe hearing loss…

  25. My son lost high frequency hearing at age 18 months from cancer treatment. He’s now 23; how can we get in touch with Frequency to see about their clinical trial?

  26. I have genetic hearing loss and would be thrilled to know if you are accepting patients for your ongoing trial to regrow inner ear hair?

  27. I’d like to know will there be a possibility of hearing loss being returned in those with hearing loss using stem cells etc anytime in the near future?

    Also will this cell research be avail in sydney australia if so how much will it cost and will there be any trials?

  28. Can it regrow hair on the head also? That would really get some interest. Personally, if it makes tinnitus less and restores some hearing, sign me up!

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