An approach to regenerate inner ear sensory hair cells reportedly lays the groundwork for treating chronic noise-induced hearing loss by the company, Frequency Therapeutics, Woburn, Mass, and its co-founders who are drawing on research from Brigham and Women’s Hospital (BWH), Harvard Medical School, Mass Eye and Ear Infirmary, and Massachusetts Institute of Technology (MIT). In the February 21, 2017 edition of Cell Reports, the scientists describe a technique to grow large quantities of inner ear progenitor cells that convert into hair cells. The same techniques are said to show the ability to regenerate hair cells in the cochlea.
Hearing loss affects 360 million people worldwide according to the World Health Organization (WHO). Inner ear hair cells are responsible for detecting sound and helping to signal it to the brain. Loud sounds and toxic drugs can lead to death of the hair cells, which do not regenerate. Humans are born with only 15,000 sensory hair cells in each cochlea, which are susceptible to damage from exposure to loud noises and medications—leading to cell death and hearing loss over time.
According to a press release from Frequency Therapeutics, sufficient numbers of mammalian cochlear hair cells have not been able to be obtained to facilitate the development of therapeutic approaches for hearing loss. The new research built on previous work to control the growth of intestinal stem cells expressing the protein Lgr5 and targeted a different population of Lgr5 cells that were discovered to be the source of sensory hair cells in the cochlea during development (a subset of supporting cells or progenitors). The team successfully identified a protocol of small molecules to efficiently grow the cochlear progenitor cells into large colonies with a high capacity for differentiation into bona fide hair cells.
“The ability to regenerate hair cells within the inner ear already exists in nature,” said Jeff Karp, PhD, of BWH and Harvard Medical School in the press release. “Birds and amphibians are able to regenerate these cells throughout their lives, which provided the base for our inspiration to find similar pathways in mammals. With our collaborators at Mass Eye and Ear Infirmary, we were able to study a small molecule approach, that we developed at MIT and BWH, to expand progenitor cells from the mouse cochlea. We believe this technique represents a major advance for hearing loss research and will enable new physiological studies as well as genetic screens using drugs, siRNA, or gene overexpression.”
The research team first focused on optimizing the expansion of Lgr5 expressing cochlear progenitor cells. With the combination of a GSK3 inhibitor to activate the Wnt signaling pathway and a histone deacetylase (HDAC) inhibitor to activate gene transcription, the research team achieved a greater than 2000-fold expansion of cochlear supporting cells compared to previous approaches. This protocol was used successfully and with consistency to generate colonies of neonatal and adult murine cells, as well as primate and human progenitor cells. Furthermore, according to the researchers, the team achieved 60-fold enhancement of hair cell production from the progenitor cells compared to current methods.
The generation of new hair cells was achieved even in cochlear tissue that had been depleted of hair cells by exposure to an ototoxic antibiotic. Importantly, hair cells produced from the protocols exhibited the same physical features, gene expression, and functionality as typical cochlear hair cells, says Frequency Therapeutics.
“This work has opened an entire field of what we call Progenitor Cell Activation (PCA), which we believe has many regenerative applications beyond hearing loss, ranging from skin-related diseases and ocular ailments to gastrointestinal diseases and diabetes,” said Will McLean, PhD, co-founder and VP, Biology and Regenerative Medicine, at Frequency Therapeutics, and the lead author of the paper. “Furthermore, the approach creates a platform with potential to explore large populations of previously difficult-to-access progenitor cell types. Drug discovery for the inner ear was limited by the inability acquire enough primary cells to explore drug targets. This approach unlocks that ability for hearing research and a variety of other fields.”
“By using Progenitor Cell Activation to restore healthy tissue within the inner ear, we’re harnessing the body’s innate ability to heal itself,” said David Lucchino, co-founder, president and CEO of Frequency Therapeutics. “Frequency’s development of a disease modifying therapeutic that can be administered with a simple injection could have a profound effect on chronic noise-induced hearing loss, our lead indication, and we are rapidly advancing this program into human clinical trials within the next 18 months,” added Chris Loose, PhD, co-founder and CSO of the company.
Frequency Therapeutics was founded to translate what the company describes as breakthrough work in Progenitor Cell Activation (PCA) by its scientific founders, Robert Langer, ScD, and Jeff Karp, PhD, into new treatments where controlled tissue regeneration with locally delivered drugs could have profound therapeutic potential. The company has licensed foundational patents from the MIT and Partners Healthcare.
Hearing Review has published several articles on work involving Lrg5, including work involving a co-author of this study, Albert Edge, PhD, and related work on blocking the notch pathway.
Original paper: McLean WJ, Yin X, Lu X, Lenz DR, McLean D, Langer R, Karp JM, Edge ASB. Clonal expansion of Lgr5-positive cells from mammalian cochlea and high-purity generation of sensory hair cells. Cell Reports. 2017;18(8):1917–1929.
Sources: Frequency Therapeutics; Brigham and Women’s Hospital; Cell Reports
Very interested in participating in clinical trials. I have had chronic tinnitus in my right ear since early ’07; still seeking some form of useful therapy to help alleviate it….
I am willing to pay
My son is 16 and lost his right hearing and suffered from tinnitus also due to labyrinthitis. I am interested to let him be on clinical trials as he is very young and hearing is important to him. Please contact me and update me on anything available.
I have tinnitus for years & I got a virus in my left ear which intensified the ringing in that ear I have maybe 10% hearing in the left &the right ear is now starting to ring now I have tried acupuncture , a natural path laser treatments & different vitamins nothing helps I was told hearing aids are my only option I hope not Im 61 & I live in alberta canada too far to drive &the boarders are closed with all thats happing please keep me informend on your results & good luck &stay safe
Can someone please contact me with an update on clinical trials? I suffer from high pitched ringing tinnitus and I would like to do something about it.
I would love to be a part of these clinical trials. I suffer from hearing loss(loud noise) as well as tinnitus.
Hello, my name is juzer and i am from Bangalore india, my son who jst turned 1 cannot hear at all….. And as per doctors advice have tried hearing aid but that too doesn’t work as he cant listen with the help of them now the only way left is cochlear implant…… But if this medicine works please let me know as i cant see my son in pain for whole his life….. Please reply i am ok if u can do a trial on my son
Cochlear implants, if recommended for your son by a doctor or audiologist, are an excellent option. Please don’t wait for an experimental drug to be developed. These things usually take quite a long time. We’ve seen near-miraculous results with cochlear implants in children, particularly if they’re implanted at a young age. Good luck!
Please let me know ASAP how I can participate in any current or future study’s or clinical trials to regrow the hair in the cochlea My tinnitus is so bad it is ruining my life. Please help!!!!
Try ayahuasca. It did not cure it for me but it helped change the frequency to something manageable. I was also able to understand the root which is helpful. The ringing was so bad before and I’m writing this now with some peace.
I have some hearing loss at the high frequencies in both ears. I have tinnitus in both ears and it is chronic, The tinnitus is worse on my left ear! This all began in September of 2017 after a bout with pneumonia, two ear infections back to back along with infected tonsils! I really need help! I would be interested in taking part in any clinical trials you are conducting! I would also appreciate getting some kind of an update regarding your current research. I am 63 years old. I have gotten to point where I do not want to live like this anymore! Please help me! Thank you for your time!
Five years ago I had breast cancer. Had a mastectomy so no chemo or radiation but developed a severe infection from fluid build-up that put me in the hospital for a week on around-the-clock heavy antibiotics. Over time, tinnitus developed and my hearing loss has increased. My left ear hearing loss is 80% but do have hearing in my right ear. Two years ago, got a set of hearing aids that are absolutely useless!! I’m going into my final semester of nursing this fall (Fall 2020). Have been working so hard and now that I’m almost done, fearing I will not be able to get a job in a hospital because I cannot hear anything high-pitched (vent alarms, bed alarms, etc) and have such difficulty hearing people talking (too much background noise). SO FRUSTRATING! Saw a story about your organization on Chronicle one night and couldn’t believe it! I would love to be part of a trial to see if I could get some of my hearing back!
They keep saying we have a cure! Wheee the hell is it? It’s been reported they found one since 2005 or earlier
I doubt these Corporate will release such cure without their multi-million business with equipment and surgeries.
Doctors and researchers are just tools to them.
happy to see a positive article like this for hear care. But sad to notice that there were no replies from the post owners.
I’m a sufferer of tinnitus and it would be a great help for my life, if you can remove my tinnitus.
Just another wild goose chase like everything else over the last half a century, with no one willing to tackle the obvious solution to sensory issues, which is organ replacement surgeries or genetic reversal. When will we realize that cochlear implants were not the holy grail hearing people were led to believe it was, as if it CURES deafness? Or that trying to regrow cochlear hair cells just ain’t working? For heaven’s sake, all we have gotten in the last half a century was VERY EXPENSIVE WAYS of trying to get people to solve their sensory issues, with the greedy manufacturer’s trying to cash in on EVERY IDEA IMAGINABLE except….CURE!! CURE!!!! WHERE ARE THE JONAS SALKS OF THE WORLD NOWADAYS??? THEY DON’T EXISTS, BECAUSE CURING THINGS DOESN’T MAKE MONEY OR SECURE PATENTS THAT MAKE THEM BILLIONS.
I am extremely interested in supporting this research, as I suffer from sound induced hearing loss, and my wife and two children (10 & 12) suffer from congenital hearing loss. Thank you
Please keep me posted on all findings.
Just sounds too good to be true.
I was diagnosed with Meniere’s disease 42 years ago.I had an operation 7 years ago to get rid of dizziness. Have no audible hearing in left ear, lost a lot of hearing in right ear. Have tinnitus in both. Would love to be in test for stem cells.
Hi Mary,. I am 52 y/o woman, diagnosed with Meniers on my 50 bday. The sudden violent vertigo episodes are completely disabling. It started with tinnitus. I can still hear only a little in my right ear. My left ear seems to be fine. Did your operation take all dizziness away? Did tinnitus get any better? Thank you,
I have single sided deafness caused by acoustic neuroma.
I would like information on this study as it becomes available.
Hi I am a 63 year old male with hearing loss due to nerve damage I’m told. I wear 2 hearing aids and this still is not enough. Love to try something that might increase my high tone hearing even. Love to hear about any new discoveries that are happening lately. Thanks Randy
I have had tinnitus for a year and it is getting worse. I have mild hearing loss and do not want to use hearing aids. Would love to be a part of this study.
HI, I just stumbled across this article. I am an 18 year law enforcement veteran. I have had complete hearing loss in my right ear since I was 12. As I’m sure you can imagine this has presented numerous struggles throughout my life. I was told the inner ear follicles “lay down” in my ear and thus the hearing loss. I’ve always been told there was nothing that could be done until the BAHA came out. Due to safety concerns, I opted to not go that route. I have always been optimistic that SOMETHING would come along. I have dealt with it well most of my life, until recently it’s become a source of lower self confidence. I am in desperate need to do something to fix this. Thank you!
I would be very interested in participating in a patient study. I have severe to profound hearing loss at the upper tone level and suffer badly from Tinnitus. Please let me know if there is any additional information I can provide to participate in a trial study.
When I finally find a hopeful cure for my long time hearing problems and tinnitus , I can’t find anyone to help me . Please please can some one send me some information how I can have this treatment. It would mean the world to me
This is my only wish in life to be able to hear
I have been told by doctors that there is no cure to repair my ear hair cells
I wish so much as I have had this problem from young age
Hearing aids will not help me , already wasted my money twice on both ears
I would love to hear the birds the ocean the rain and most of all my grandchildren
It would be s dream come true
could this work for a 6mo. old baby who was born with a hearing loss due to lack of hair cells?
To the Author :I strongly believe in the ATA as well as research (especially yours. I have tried everything and nothing works. I have subjective tinnitus which literally puts me down due to headaches and nausea as well as loss of sleep. Im willing to help determine outcomes of potential medicine. im desperate for some quietness and pray that we all get some form of relief.
Please email me if I stand any chance of participating in a trial I would be truly grateful. (hearing aids do very little) Thanks and good work.
Please let me know how to participate in this study.
How can I obtain information on the progress and availability of treatment for hearing loss and tinnitus?
Hi Please can you help me. I am suffering with bad hearing loss. I am still young but at the point of loosing my job due to this.
Please let me be a part of this study. I was bombarded with the sound of explosions/bombs at a high decibel level. I am a teacher, the tinnitus is ruining my job and my marriage and my entire life. PLEASE include me in this study. My email is above. Cell is 3303182254
Does this treatment consist of injections in the inner ear?
In February 2017 you expected to advance to human trial in eighteen months. what is the state to day. I am 68, female. Hearing deficient from childhood. My right ear is dead 40 years ago through a stapidectomy operation and left ear loss is 95 – 100 db and still loosing due ‘Amiodarone’. If you succeed I may hear something nicely at the fag end of my life. May God bless you.
Im 36 male, i got tinnitus on both ears 6 months ago due to expose of antibiotic (clarithromycin). I would like to receive updates of your study.
I have moderate hearing loss in both ears from the dying off off inner ear hair. I am 55. I am interested in participating in the clinical trial.
I want to be part of the clinical study. How can I sign up?
Are there any test groups for regrowing hair in the ear ? My son suffers from this hearing loss
57 year old male with about a 10 kHz hiss in both ears for last 3-4 years but recently louder. My tinnitus probably due to loud equipment ie. chainsaws, circular saws….
I’m very excited about the work being done at Frequency Therapeutics and would be very interested in volunteering when you start human trials. Thanks and keep up the good work!
Please contact me with any new developments. We are in need of help. In am suffering right now.Piece of mind and the removal of this noise in my head would be my wish of I had one. I’m am praying that u guys are on to something that would help millions including myself. We need your help and are greatful for your concern. I would love to be in a study that is this groundbreaking.please keep me updated.
You’re research studies and findings are fascinating.
I’m a 68 year old male suffering from hear loss and Tinnitus.
I’m in good health otherwise.
I’d love to participate in your clinical trials.
Very interesting. I wouldlike to know if there is some similar study in Europe or in Italy and how I can stay in touch with your research.
Thank you very much
Very interested in your researcha ya 47 here w lose of hearing and tinnitus constantly feel free to let me know if and when you want to test on humans!
I have loss almost all my hearing in what once diagnostic as Meuniere disease later on it was rejected as the cause of my titinous and hearing loss. I am now considering the Cochlear Implant option; however this will not really correct my hearing problem but bypass it. This research is something that interests me very much. How can I get in contact with this program?
I have hearing loss to my right ear, the doctor was unable to tell me why, labs were done and MRI was done and we found nothing, I would like to be a candidate for sterocilia restoration, please help, I’m only 31 years old.
I was in the Military for 24 and I have none stop ringing in both my ears. Let me know if you need people for the clinical trials.
I have loud sound damage to my ears with a nasty echoing in my ears and hearing aids just dont do enough, I still can’t pull out the speech in a crowded loud room. I would be happy to be a test subject.
I have a SHNL hearing loss in both year m 22 years old and desperately want to reverse my hearing ability please help us all
I am very interested in becoming a subject for your Clinical Trials..I suddenly lost my hearing in my right ear while on the phone in 2001.I got a loud machine like sound in my ear and suddenly my hearing was gone..went to the emergency room and was not treated properly..the hearing loss happened on a Saturday and was not able to see my doctor until Monday..I also got a bad case of vertigo a few hours after the hearing loss..it took me four months to find the right doctor to tell me I got a virus and if I was given Predisone within 48 hours it would have saved my hearing..it was too late for me the damage was permanent..I also have severe tinnitus in that ear..it’s so loud I can’t hear out of my good ear..sounds like thousands of insects in my ear with the ocean on top of it..if you’ve found a way to restore the hairs in the inner ear, I’m definitely interested in becoming a test subject..I just want my hearing back and silence in my head..
Omg you sound like me! Right ear and on a Saturday morning..but I was asleep when I lost it…
Also I was misdiagnosed too! My gp told me to “pop” my ears…then to get a hearing test which I couldn’t book until Monday..but they also said they had no booking until 2 weeks…there goes the time where I could have saved my hearing…but like you..I didn’t know!
I have gottem chronic extreme loud tinnitus due to djing. Is it possible this could help me? Im still really young and hope for a cure or at least some relief please?
Kind regards Bahar
I have been following this study a bit through KU med center. I have hearing loss and am eager to find out if I could be helped as well. I am relatively young to have hearing loss. I am thankful hearing aides help but I am active and would love not to need them.
I am a sufferer of acute Tinnitus.It’s so bad I can’t sleep at all…..Based on my understanding of the Tinnitus ( mine was caused by sensory neuronal damage) regeneration of stereocilia my help Tinnitus sufferers… How many more years do you think it will it take to achieve the knowledge/techniques necessary to actually try this on humans ?
I am also waiting please help hearing loss pateint.Save humanity