Newly formed cochlear hair cells contain intricate hair bundles with many stereocilia (critical for sensing sound) and other components that are critical for proper function and neural transmission. Credit: Will McLean
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.
Jeff Karp, PhD
“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
Sudden hearing loss occurred in the evening of August 1, 2018. The high frequency of my right ear was severely damaged and there was a 24 hour high frequency tinnitus. When the doctor told me that this would accompany me throughout my life, I felt very hopeless. I’m only 20 years old. I don’t want to go on like this anymore. When I looked around, I found fx322, which I thought gave me hope that I could regain my hearing. Try again to do what I like, and God bless you.
I hope this effort and research is occurring and progressing. I suffer from profound loss (high frequency) in both ears. Hearing aids haven’t been helpful so regenerating what’s been lost would be a dream come true! I miss so much of what I heard for many early years as this loss has been a decline for 20 years – I am otherwise in good health and mentallly strong @ 66. I would like to be considered for any study that could change the years I have left … so MANY others suffer too! I read lips and try to stay socially active but voice distinction is nil even though I hear voices and low frequency sounds – thank you for this hope!!
I have hearing loss in both ears please help
Very interesting and I thank you that at least someone is trying to find a solution to this problem. I too would be very keen to participate in clinical trials in South Africa JHB, I have 80% low and 0% high tones in both ears, so it would be great to get these hairs growing and giving us normal hearing again. Thank you for your hard work.
I too am suffering from acoustic trauma hearing loss and constant tinnitus and wish very much to participate in your program that might offer relief and perhaps even cure. Please help me get out of the constant torture.
Hi,
I am a 52 year old woman, who has had tinnitus in both ears for the past 7 years after taking ototoxic antibiotics. I have to have white noise/quiet music etc. playing to be able to fall asleep as I am bothered by the ringing mostly when it is silent. It makes sense that the hair cell loss could cause tinnitus, and this treatment is very promising. Thank you so much to all involved in this great work.
Pls update me about this thing pls I m suffering from Tinnitus pls help I m only 21 pls for God sake lks help me
35 years old. Lost hearing in left ear at 22. I would like to participate in study. I live in Connecticut and I will travel for study.
would love to participate in any study or clinical trial. I have Tinnitus in both ears, more on the left, which came on suddenly in Feb of this year when I was treating ear wax blockage. I believe it was the Debrox solution, and me applying too much of it-
Thanks
I’m 44yrs old and I have sudden hearing loss in my right ear. It’s been about 5 years now. I went to two different doctors before they finally sent me to ENT doctor in which they tried steroid shots twice but it was too late. I’d love to be able to hear again, talk on the phone on my right ear again and hear where noises are coming from!
Thank you.
When& where I get that medicine?
Is it hepfull in 65% sensory hearing loss ?
Please inform of pilot use and will be keen to support.
My daughter is aged 13 and keen to be in trial. Please help contacting me . Thanks
I would be very interested in this development as my hearing has been badly affected over many years through loud sounds as a result of playing music.
I also have had two liver transplants 14years ago.
I have had tinnitus and high-frequency hearing loss for many years due to career-related noise exposure. My ex daughter-in-law , an AuD, told me this was coming. I would like to be considered for the human study portion of this research.
Bob Lewis
I have zero hearing in one ear following the onset of Meniers 15 years ago (which has now burnt out) and have been wearing a hearing aid in the other ear for 2 years. I am 60 years old and would be very happy to participate in any trials on either my ear effected by Meniers or indeed both ears.
Respected,
I have a seven year old girl. She has progressively lost her hearing since her sixth year and right now is on the right ear completely out of hearing and on the left a very severe damage. We plan to put the cochlear implant on the right, but this text gave us hope that we might be able to do something else to help her. We are from Montenegro and here are doctors and they will not tell us about possible options beyond the cochlear implant. The girl was still in the stomach with CMV infection (ninth month), asphyxia on childbirth, but sudden hearing loss occurs in the sixth year after a month of MMR vaccine. Please if you think that there is a chance that your way will help us to guide us to work ….
all the best
Irena Iri
Hi im from india suffering from tinnitus meniears disease for 5 years with hearing loss in my left year and also episodes of vertigo please help me this article gives me hope as im suffering from depression and suicidal thoughts because of this
I have a tinnitus in my right ear which led to complete deafness and the left started the same chronic sound,%60 hearing left as hearing test shows, I’m ready to volunteer to run your experiments on my both ears,to me it is a waiting time to be deaf in both ears, I can take the risk, either you fix both of them or I will be deaf anyway, I prepare myself for this bitter fact. Please contact me if you are looking for volunteers for your research.
Hi I have had tinnitus for the past 10 years since last year june it developed to severe tinnitus saw a specialist I have damaged inner and outer cochlea hair cells its the high pitch sound which is effected this is due to my work which I am a boilermaker welder if there is any medication to regrow the cochlea hair or i am prepared to volunteer for any research I don’t drink alcohol or smoke.Please help Thank you.
Hi
Very keen to be candidate, female in my 30s and in good health
Would rather seek alternative options then implant
Please keep me in mind
SIR
My son two years old is suffering from profound hearing loss. According to ASSR report he listen between 70db to 80db. Is he be able to use your medicine. Please reply as I am from India. And I want to know if my will get cured by your medicine
I am willing to offer myself for research and drug trials. I am a victim of Antibiotic overdose. Please feel fre to contact me and I dont expect any monetary benefits.
Thanks
I am very keen to have this for me, I am 38 and have started loosing my left ear with tinnitus, 70% is already gone. It will be a life-changing help for me to get my life back
I would love to participate in this study. I have idiopathic sudden severe hearing loss in my right ear. February 2018 I simply woke up one morning nearly deaf on my right side. I suffer from bad tinnitus on the right side as well. I can still communicate as my left ear hearing is nearly normal but its much more difficult. Please keep me informed. Thank you very much for your great contributions to science!
Very interested in any updates, after years as a Military diver my hearing reduced considerably, 5 years ago after a recreational dive I had total loss of hearing in my right ear, medical specialists advised it would be 50/50 if hearing returned but sadly for me it did not, hearing loss is so severe that hearing aids are not an option. Would be happy to be part of any trial if the opportunity arose.
I am Indian running 70 years. I have the problem of hard of hearing since from my infant days of about 4 years when I contracted Typhoid fever and when my brother administered wrong unknown drug resulting in continuous pus percolation, tympanic membrane teared out. No treatment in those days. Partially conductive defect is restored when I was 23 years old. I am having mixed defect which necessitated regrowth of hair cells. My eyes are on research outcome. I have cut miserable life and hoping to die as a normal man after hearing good sound and enjoyment. I request to let me know about the development in this field. I offer myself to be used in research too.
I have just been diagnosed with tinnitus in my right ear it is horrible to live with. Would like to hear of any future studies so I can get some relief. Please put me on any email list when you have a breakthrough would like to be considered in a trial study, I live in Montgomery Illinois. Keep up the awesome work your doing Godspeed your progress.
I have got damaged nerve endings due to measles when I was a child. I’m 46 now and have been praying that something could of been done by now. Being deaf in one ear has destroyed my coincidence. I’d love to trial anything to be able to hear properly again .
My daughter is 28 and is deaf in right ear due to strepnamon menegitis at the age of 14 months old. It would be wonderful if her hearing could be restored.
I have severe hearing loss in my right ear and mild in the left ear, also suffer with tinnitus.
Please put me on your mailing list for updates.
Thank you
Hello,
I understand that I have come upon
this article quite late, but would like to join the discussion. I am a 46 yr old male who lost hearing bilaterally due to an ototoxic reaction while in Shands UF burn unit. I have a cochlear implant left side and my right is at 1-2% remaining natural hearing. Could someone please contact me regarding these most promising developments. I am willing and able to travel to any location to be part of a study and or be examined to help further this research. Will gladly share my cell number upon request.
Respectfully,
David H. Boeck Jr
Hello David, I would appreciate also if you find where and how to join the study. I lost most hearing in my right ear because of a PI who knew nothing about curing a simple ear infection for 4 months, then gave me the wrong antibiotic, then put a “super power washer” in my ear and literally blew a hole in my ear drum! had surgery which did not improve much. I need the hair regeneration therapy etc, I think. But am open to studys, etc on any new developments. Please pass any knew info my way. Thank You and good luck to you as well.
I am 35 years old and have worn hearing aids since I was 18, although after college I stopped wearing them until I needed to get another pair to interview for a job. Now my employer wants my hearing tested for an advancement and an audiologist suggested I look into a cochlear implant. This scares me. I’m a new father and would very much like to be considered for a clinical study for this procedure if at all possible. Thank you.
Eric. May 27, 2018
Very interested. Please contact me if I can be considered. 43 years old. Hearing loss since infant. Suspected to be as a result of Kanamycin. Very stable hearing loss until the birth of my third child at 39. Developed tinnitis 3 months post partum. One ear with significant drop in speech recognition.
I’m a 26 year old cochlear implant recipient. I suffered from sensorineural hearing loss, due to bacterial meningitis at age 8. Can FX-322 drug help me hear again ?
I have had tinnitus for 30 years due to a severe ear infection.All of the hair on the cochleas was destroyed by my ear infection. I would be very willing to be a patient for your clinical testing in the future.Please e-mail me if this would be a possibility in the future. My name is Joel Anderson and my e-mail address is [email protected]. I live in San Jose California and my telephone # is 408-629-1835. Thank you for your research.
My daughter has suffered from imbalance due to Pseudomonis and the killing off of inner ear hair cells. Levoquin was the culprit. It’s been years now; more than 12 and with bad weather it’s horrible. How can you help her?
Keep me updated please. I’m 49 years old & have mixed hearing loss in left ear (conductive & sensorineural) from ear infection in 2012 in which my eardrum ruptured, ent thinks it was caused from a virus. Now just this month on April 8,2018 I developed an ear infection in my right good ear. I went to ent within 48 hours hoping he would give me the steroid shots in my right ear like he did in my left ear, but it was 2 months after infection/ hearing loss when I got injections in left ear. Anyway ent said he thought this was just a really bad bacterial ear infection in my right ear & to follow up with him in two weeks which I did & found out after taking hearing test that my high frequency hearing loss is now the same in both ears & he now thinks this was caused by s virus! So frustrating! Anyway I used to be able to tolerate the ringing in my left ear before the hearing loss in my right ear occurred, but now the ringing in left iseems to be 10 times louder than before & I also have some ringing now in the right ear but I don’t notice it as much because left ear ringing is so loud. I also have had distortion in my left ear & now I have it in my right ear, where when you turn music up it sounds like s busted speaker. I think I’m going to lose my mind, because nobody in my family understands & when I ask them to turn down music they say I thought you couldn’t hear that good. They don’t understand the louder the noise the more distortion there is. Anyway I know this ringing in my ears is from the hearing loss, because I never developed any ringing in either ear until I developed hearing losses in both ears at different times. Anyway PLEASE KEEP ME UPDATED ON A POSSIBLE CURE FOR THIS! Thanks so much for your continued work & research on this conditiion.
I wanted to ask if you knew about colloidal silver and ultrasonic nebuliser the tiny silver particles kill off any infection, virus or single cell organism, mold and fungus. highly effective for sinus infections without antibiotic side effects. just google the terms on amazon or ebay its worked to improve my hearing and get rid of tinnitus.
Hi, As a teacher I am very interested in your research. I have bilateral ‘moderate’ hearing loss from damaged hair cells. I started losing my hearing when I turned 36 and now at 55 I rely on hearing aids. Unfortunately, the hearing aids are not a panacea, and I often have trouble hearing the young children I teach. I love my profession with all my heart, but my hearing loss makes it more and more challenging each year. I would love to be involved in your clinical trial…if not, I would appreciate updates as to how it is progressing. Thank you for your wonderful work in this area….I’m very hopeful things may turn around for me and I will be able to enjoy a long career fulfilling my passion as a teacher.
I have had a gradual loss of hearing over the last 3years and recently had a hearing test.
Moderate to severe loss of hearing was the
result. Do not like the idea of aids but more than intrested in your stem cell implants.I am 70 in very good health apart from hearing which could possibly be work related. I would be more than willing to take part in your research program.
Regards
Gordon
Hello Gordon, I am also interested in the Stem cell implants or hair cell regeneration etc. Please send me any info you may receive. I would greatly appreciate it. I am 61 and lost 60% at least in my right ear due to a quack pa who couldnt’ even cure a simple ear infection for 4 months, then literally blew a hole in my ear drum with a power washer! Hearing aids are horrible and will not work for me…..was more dangerous than my hearing loss. At least what I can hear, is normal, aids are very misleading or direction etc……..I really need help on getting this restored if possible. Thank You and good luck to you as well.
I am very impressed with the progress that has been made over the last number of years in the field of hearing regeneration. Like everyone else that has commented I would be more than happy to become involved in any future studies.
Please keep me updated on this research. I had my eardrum in my left ear to rupture back in 2012 after a ear infection & the ENT doctor thinks it was viral & I now have both conductive & sensorineural hearing loss in left ear & my right ear was good until just about 3 weeks ago on April 8, 2018 I woke up & could not hear out of my right ear & went to doctor who gave my steroid shot & antibiotic shot along with prescriptions for both to take & I went to ENT doctor two days later who said he thought it was really bad bacterial ear infection & told me to follow up in two weeks with him & when I did he now said he believed it was viral. Anyway now I’m left with ringing in both ears & I could tolerate the ringing when it was just one ear but now that it is both ears the sound seems must louder!
My right ear high frequency is bad as compared to my left ear. I am willing to travel to meet u for further treatment.
I hv got treatment in Singapore n their advise is to use a hearing aids. The hearing aid does not work well despite a few frequency adjustments.
I think only by genetic treatment my hearing can improve.
Grateful if u can advise further treatment
I have had severe tinnitus since 1990 due to a ear infection which destroyed the hair stereocilia on my cochlea.I would like to be a candidate for your research Email me if this would be a possibility.
have noise related hearing loss in both ears and schwannoma in one ear. The schwannoma is small, and i’m just observing it at the moment. I would be very interested in learning more about your study to try and improve the noise related hearing loss
My son is twenty months old. He’s suffering from profound hearing loss. According to ASSR report he listen at 80db.i want to know is this medicine will help him to get cured. Or not. And how can I get this medicine and treatment. Please reply. I will be eagerly waiting for your reply.
Is this medicine now available and can it be used to cure it..
My son is deaf in his left ear and has hearing loss in his right. This is due to meningitis. Would he be a Candidate for the regeneration of hair follicles. My son is 17.
My son in law is nearly deaf in one ear and has some loss in the other. He has been told he is not a canadate not a candidate for the cochlear implant until 6 months after he has lost all hearing. Would you please put this young man on your list for this trial treatment.
Hello i am 33 years old with almost 2 years old tinnitus either from loud noise or anxiety caused tinnitus. Let me join in your hair growth inner ears