A study led by investigators in the Eaton-Peabody Laboratories (EPL) demonstrates an improved way of studying hair cell regeneration in the inner ear, moving scientists closer in their quest to developing new treatments for permanent hearing loss.
Over 400 million people worldwide live with sensorineural hearing loss, which occurs most often when hair cells, the cells in the inner ear responsible for hearing, deteriorate. Aging, infections, medications or exposure to loud noises can damage these cells. There are no built-in replacements for the damaged hair cells – they become permanently lost, resulting in irreversible hearing loss.
Scientists have sought new ways to regenerate hair cells in humans by looking toward other species for clues. Non-mammals like birds and fish, for example, can regenerate damaged hair cells. Identifying which molecular pathways allow hair cells to regenerate could help researchers better understand the mechanisms needed to reverse hearing loss. However, studying these pathways has been a challenge for researchers who have long relied on complex mouse models and a limited set of relevant tools in a dish.
“One of the biggest challenges has been the limited number of cells in the cochlea and the lack of high throughput models to study hair cell regeneration,” said Dunia Abdul-Aziz, MD, an EPL investigator and ENT surgeon at Mass Eye and Ear. “With the advent of inner ear organoids, we can now robustly study this process.”
Dr. Abdul-Aziz and Albert Edge, PhD, director of the Tillotson Cell Biology Unit and principal investigator in the EPL, have recently reported a novel approach that combines genetic tools with organoid technology to uncover a promising pathway involved in hair cell regeneration. In their study published in Stem Cell Reports, they reveal a new molecular player called “hypermethylated in cancer 1,” or “HIC1,” that hinders the regeneration of hair cells in mammals.
Their finding could change the way researchers study hair loss restoration for years to come.
A new way of testing molecular pathways
Scientists studying the brain often run into the same issue facing scientists studying the inner ear; brains and inner ears can only be closely examined upon autopsy, therefore limiting how much researchers can learn about the function of their tissues. The emergence of organoids, or artificially grown tissues and cell masses, has changed how scientists have approached translational research in recent years.
“Organoids are being used to study cells from pretty much every organ in the body; for the brain, skin, intestinal epithelium,” explained Dr. Edge. “Our identification of cells in the cochlea that could multiply and turn into hair cells has made it possible to grow cochlear organoids in a culture system and manipulate different factors to study their effects.”
Testing hair cell development in a mammal’s inner ear typically requires an abundance of cells called progenitor cells, or stem cells, that are capable of being differentiated, or turned into, hair cells. In need of a sufficient amount of progenitor cells for testing, Dr. Abdul-Aziz and Dr. Edge turned to their new organoid system. They built the organoid by first isolating and expanding progenitor cells from newborn mouse cochlea. Then, they genetically modified the organoids in a way that allowed the team to specifically target specific proteins. After 10 days, the cochlear organoid was ready for testing.
Targeting the gene responsible for hair cell development
Understanding why hair cells naturally regenerate in some species and not others begins with the gene ATOH1. Across species, ATOH1 is an essential gene required for hair cell development. Progenitor cells differentiate into hair cells in the inner ear through expression of ATOH1. And, while non-mammals, such as a bird, can replace damaged hair cells throughout their lives, mammals lose this function after their first week of life.
Through a series of previous studies, scientists have learned that hair cells cannot form without ATOH1 and that more hair cells can be made by overexpressing it. Understanding what factors repress ATOH1 holds significant promise for hair cell restoration. Previous studies indicated that the protein HIC1 repressed ATOH1 in the brain and in the intestine. These studies encouraged Drs. Abdul-Aziz and Edge to hypothesize that HIC1 may contribute to silencing of ATOH1 and the differentiation of hair cells in the inner ear. Their study would be the first time HIC1 had been tested to modify hair cell regeneration.
In the new study, the researchers used genetic tools to limit the expression of HIC1 in cochlear organoids and observed changes in ATOH1 levels. They saw that ATOH1 expression increased, and moreover, that there were markedly more hair cells generated from progenitor cells. Conversely, when the researchers overexpressed HIC1 in the organoid model, they witnessed ATOH1 inhibition and a subsequent decrease in hair cells. They went on to study the mechanism of HIC1’s repression, which is caused in part by modulating a key developmental pathway known as “Wnt signaling.”
“Fundamentally, we seek to understand how ATOH1 and other hair cell genes are regulated,” Dr. Abdul-Aziz explained. “And by targeting these pathways in future studies, we might be able to help spur hair cell regeneration in the inner ear.”
Future expectations for hair cell regeneration research
Drs. Abdul-Aziz and Edge believe that finding ways to promote and control ATOH1 expression will be crucial to reversing hearing loss. According to Dr. Abdul-Aziz, HIC1 is one of many factors playing a role in regulating hair cell development. Their findings will provide researchers with a logical approach to test other candidate regulators in addition to HIC1.
The findings verified a novel system by which other molecular pathways can be studied. The organoid model, and the genetic toolkit, can be adjusted to test countless other genes and regulators, all of which could help move researchers a step closer to restoring hearing.
“This is a big step forward in the exciting work being done in the lab to understand what prevents mammalian hair cells from regenerating,” Dr. Edge said. “The sky is the limit with these organoid models.”
Funding for the study performed by Dr. Abdul-Aziz and Dr. Edge was made possible by grants from the National Institute of Health, Hearing Health Foundation, American Academy of Otolaryngology, American Neurotology Society.
Good Morning Doctor,
I have recently had radiation for my acoustic neuroma. I have no hearing in my right ear. Would I be a good candidate for this? Thank you. Stuart
Hi Stuart, thanks for reading and your comment. This work is early and not yet in clinical trials so it’s impossible for us to say who is a candidate, but we hope to continue to update our readers about this work.
I suffered sudden total and final sensorineural hearing loss to my left ear in April this year. It happened in the middle of the night, was frightening and I’m still adjusting to the change it has brought to my life. I have age related hearing loss to my right ear and now have a hearing aid to optimise my hearing ability. My balance has been affected and I have tinnitus in my left ear now. Also I’m a drummer and it’s my passion, I play in a rock covers band. I’m 70! But this article has helped me and inspired me. Thankyou. I hope in my lifetime I may benefit from this wonderful research. Best wishes, Chris.
Thanks for reading and sharing your story, Christopher. Our researchers are hard at work, working towards a cure for permanent hearing loss.
Do we have any idea of a timespan to treatment being available?
If a way is found to regrow hair cells and restore hearing then
those geniuses should be nominated for the Nobel Prize for Medicine.
It would be a miracle for people like myself who have had sensorineural
from a very young age.
Please do put me on the test list I would be more than happy to be one
of the first to try this out for real.
Hi Michael, thanks for reading and your comment. While we don’t have an exact time table, research takes time to reach clinical trials, and we will continue to update our blog as more research comes out.
Wow. Nice work—Hope I’m around when this starts being feasible for human application!!
Sounds like you’ve developed not just one new platform for performing research, but s whole new method of approaching platform development. Well done!!
Thanks for reading and your comment John, it’s exciting work we hope one day will be of great impact.
This is exciting news. I have endured numerous ear surgeries beginning at age 2 1/2 and now suffer from significant hearing loss, some of which is caused by the loss of hair cells as you describe in your research. I would like to learn more about your research and participate in any clinical trials you might be undertaking. Thanks so much, Diane Caggiano
Thanks for reading Diane, we’ll continue to update our blog as more news comes out on this research and other research designed to target and treat hearing loss.
Are you looking for someone to volunteers to see if works.
Hi Hartley, thanks for reading. The work is too early for clinical trials, but please stay tuned to our blog for updates!
Hi! The article was very interesting to read and it seems like might be hope for people with hearing loss. I’m wondering if people with auto-immune diseases, like myself, would be a candidate for a trial if one is established. I spoke with a dr. A few years ago about a study going that focused on the regeneration of stem cell hair growth, but I could not be a candidate for participation because of my auto-immune diseases.
I am T1 diabetic, and I have Cogan’s syndrome as well as Relapsing Polychondritis.
I guess I’m just curious about who may be a candidate for a trial if there ever is one.
Hi Jennifer, thank you for sharing and your comment. While it’s too soon to talk clinical trials or criteria for enrollment, we hope to update our audiences as this work progresses.
I heard about this a few years ago – but nothing since. This would be a god sent. I was told to purchase a hearing aid for my right ear (I cannot hear anything) that will transfer the sound from my good ear to the right ear. Cost 4500. since a regular hearing aid, is useless.
I too would like to be notified when clinical trials start. This could benefit so many people like me. Thank you for keeping at it.
Thanks Renate for reading and your comment, we appreciate your support!
How does this relate to congenital hearing loss involving multiple members of a family line?
Please keep up your great research. Many people –I’m sure—appreciate all the work going into such a great project.
This is such exciting news! I have been a patient of Dr Daniel Lee at Mass Eye & Ear since 2017….I would be first in line when you need volunteers!
Hello Sir. Myself having noise induced hearing loss at age of 45.Kindly help if any medicine available to repair damaged hair cells
Its Really exciting news. I am 83 and losing hearing in my both ears. Could use the medication for trial if needed and available to tryout. Million thanks to all of you. in fact more younger people can get the best of it than older people,
Recently have hearing loss and muffled sounds due to shotgun blast near my ears. Lots of ringing and buzzing. ENT and audiologist tried steroids. No help. Tried hearing aids, no help. Do you have any recommendations? Thank you.
Hi Scott, we can’t make personal recommendations over the blog, but if you’d like to see a hearing specialist at Mass Eye and Ear, you can call our Audiology department at 617-573-3266. https://www.masseyeandear.org/specialties/audiology
Dr. Ive been reading this about trying to grow hair for years. You say it’s still too early to start clinical trials. It feels like false hope after so many years.
The other thing is I don’t see mention of any possible research being done on Menieres syndrome.
How do I sign up to receive updates.
Hi Ellen, you can receive updates on our research through our blog by signing up here: https://focus.masseyeandear.org/subscribe/
GOOD DAY , DOCTOR .
Am wearing OTC hearing aids for the past 8 yrs. or so.
Have ringing in my right ear since early this year , but my leftear occassionally has ,too. Sad to say , I donot regularly use it , for the reason that it was quite bothersome & would like keep it longer .But, now both are having statics ,whenever it’s ON .
I have to always adjust my hearing aids ,drpending on the occassion or sourroundings .
I had streptomycin sulfate injections ( daily for a month) for my lungs problem( early 80’s). And some other medicines . Thankful that I am now in good health condition , inspite my age at 78 .
Is there still a chance for me to reverse my ailment ?
Thank you .
Hoping for the best of your research.
Hi Hilda, thanks for reading! Our researchers are hard at work developing new treatments for patients and we’ll continue to update our blog as more information comes out.
I just want to say, may God continue to support and give you wisdom for your work. God bless your efforts.
Keep me informed for my hearing loss and your progress on hair cell treatment.
Please work hard with your group and hurry. God’s hands are on you Our prayers are behind you Please keep us updated on the progress of your research
The ability to regenerate tissue that doesn’t normally grow back (ear hair cells, teeth, etc) is in my opinion the most exciting thing going on at the moment. If one day there was a pill (or course thereof) one could take to overexpress ATOH1 and recover lost hearing, a lot of lives would be changed. Covid has shown us that we can develop a vaccine in a record time if enough money is thrown at the problem. Perhaps it’s time we start throwing money at this sort of thing. It’s a very exciting time to be alive for sure!
Thanks for publishing this informative article.
I have currently loss all hearing in my right ear and losing my hearing in the left due to Meniere Dz. , I am looking for someone that would allow me to be a candidate for research on reversing the hair loss- do you know of any current or upcoming studies that I can be involved in.
Amazing! Keep up the good work! The inner hair loss in my family is genetic. There was no cure for my grandpa, dad, and now both me nor my brother, but hope things change for my son. Your work will change lives!!!
Thank you for reading and your comment, Jennifer, we hope so!
I hope they continue this research and have enough funding and agency to continue!
It takes just a TINY portion of damage cells to cause chronic tinnitus.
If they could fix this problem for millions of people, it would pay back in spades and help millions .
Thanks for article.
Very commendable what you are doing. Keep up the amazing work. My son has hearing loss as an infant. He is a twin. I wonder if being a twin could introduce any new ideas. Just throwing things out there. Looking forward to seeing your progress.
I truly hope clinical trials will start in my lifetime. I would very much like to participate. I just want to hear and understand y grandkifd.
I’m just wondering if I would be a candidate for this at all? I am 74 and about a decade ago I had sudden hearing loss in my right ear. My right ear is totally deaf. Would this help me to regain Hearing in my right ear? I have 90% of my balance. And I have learned to live with this but would love to be able to hear again the way I used to.
Please put me on the list for volunteer. I would love to hear again without cochlear implant and hearing aid. I keep loosing hearing in the hearing aid side and I do not want another cochlear implant. God bless al of you. There are many of us out there
FASCINATING!! WHAT IS LABYRINTHECTOMY? MY FRIEND HAS MINERES DISEASE…MAY NEED SURGERY????
PLEASE SEND INFO. H0W TO FIND THE RIGHT DOCTOR
Are there any stem cell trials planned for stem cell regeneration for Cochlear nerve cells? I have Tinnitus and am retired and would like to participate in trials at the mass eye and ear.
Exciting news… yet still frustrating because for years and years we’ve been hearing about these types of solutions with nothing to show for it. I know I sound like a debbie downer but a real cure for hearing loss is still very far away. 10, 15, maybe 20+ years. I think they will get there but not anytime soon unfortunately.
I am a nonagenarian with severe hearing loss, wear two hearing aids that do help and follow medical research as often as I can. When young, I sustained a left-sided skull fracture, caught scarlet fever and suffered a severe blow to my right ear as an adult, resulting in severe tinnitus for years that has recently subsided. Would donating my body for science help research in studying my body, specifically the ears?
Is there a clinical trial for sensineural hearing loss that will be available?