> Despite the progress in our approach to achieve HC regeneration in the adult cochlea in vitro and in vivo, major challenges remain before potential clinical applications. First, regenerated HCs need to be terminally differentiated and fully mature, and to be located in the sensory epithelial region such that their stereocilia contact the tectorial membrane to mediate the mechanoelectrical transduction, as well as be able to survive long term. The current regenerated HC-like cells are immature and the time frame we used is not ideal to determine their long-term survival. One potential reason for the lack of terminal differentiation is the continuous Atoh1 expression mediated by adenovirus, which is known to impact HC maturation and is detrimental to HC survival (9, 56). Future studies to express Atoh1 transiently in the reprogrammed SCs could address the issue. Second, the surgical procedure of “cochleostomy” in the adult cochlea severely damages the microenvironment of the cochlea including extensive OHC death around the injection site. Future studies using an alternative delivery vehicle with a minimally invasive surgical procedure such as an AAV with round window injection could significantly improve HC regeneration efficiency without causing trauma to the inner ear. Third, major efforts should be made to identify/create new AAVs or novel delivery vehicles such as nanoparticles capable of targeting adult cochlear SCs for reprogramming. Finally, the restoration of hearing in adult deaf animal models significantly and reliably by HC regeneration will elevate the field of HC regeneration to a clinically relevant stage.
It sounds like the authors have found a more effective way to trigger generation of immature Hair Cells than was already known, but they're several large steps away from "restoration of hearing in adult deaf animal models".
However, the submitted article (from hms.harvard.edu) summarizes the findings as:
> [Authors] reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear.
While it's not outright false, the "successfully regenerated" isn't the way I'd interpret the PNAS paper. Perhaps I misread the paper.
Thanks for adding this context. As someone suffering from SNHL with a great wish to have some of my hearing restored, headlines & articles like these often give my a sense of hope for a near-term solution that turns out to be false. I wish (pop)scientific news would be a little bit more nuanced/careful..
Anyway, great that another small but significant step is made in this terribly complicated problem :)
Same here - suffering from Sensorineural hearing loss since I was a kid. Lots of hope but not seen a ubiquitous or even an experimental solution in sight.
Hearing is complicated, this is a repost and it's believed many components need to be fixed in order to hear again. A drug (FX-322) was pulled recently after reaching stage 2 clinical trials and had good evidence of regenerating hair cells via progenitors in mice and cadaver.
Hair cells are not even considered the first thing to be damaged when one notices hearing loss. It's considered neurons connecting the audiotry nerve to and from the hair cell via the spiral ganglion cell are lost (both neuron and eventually the cell after a few months/years).
There is currently no way of reconnecting these or regenerating the SG cell.
I also think funding in this area is extremely low (looking at DoD and UK govs commitment's). Given the funding available I think researchers have done great but more money is needed.
The article seems to suggest that the SG cell is also getting regenerated. See
> The new cells contained transduction channels that relay sound signals and the ability to form connections with auditory neurons — processes essential to hearing.
Incredible I think I missed that part. Afaik the only other drug shown to regenerate synapse in animals was a Bisphosphonates (Zoledronate acid).
There's further questions on the models. Using Guinea pigs and mice yeild different outcomes. There's also questions on whether adult mice are better suited for hearing research.
My family suffers from a mitochondrial disease in which effects these very hairs in our cochlea (which makes us great candidates for cochlear implants) but would this be "simple" for research such as regenerating hair cells?
One of the reasons we make such good cochlear implant candidates is we instantly hear. It's like the neurons/links were just waiting.
If this is of interest to you, or you could perhaps point me in the direction of someone in this space, you can find my via my profile :)
I also thought of fx322 and oto313 (from another lab). Hearing regeneration and tinnitus healing are those things that seem "achievable " but are way more complicated than it seems initially.
The subreddit r/tinnitusresearch has good coverage of the scientific efforts. Which as you mentioned are not that many.
The trials have shown some degree of efficacy above controls. At this stage I only consider evidence from trials to get excited over, though it's important to be optimistic over lab results and research.
When I first starting doing more research I was surprised by the low funding and the fairly big number of affected patients. Why is there not more funding? Research is making steady progress so the field doesn't appear to be a money sink with nothing to show for.
Can you point me to some sources that back up your claim that neurons are damaged first and only later hair cells are lost as well. I always thought it’s the other way round.
Of course. There's an good video explaining this and also citing / explaining the same research. I made a error in my original post, it is the synapse* not neuron between the SG and audiotry nerve, and the IHC / OHC.
Hidden Hearing Loss: The Effects of Synaptopathy, Stanford.
I think there are different forms of hearing loss (hidden hearing loss, noice induced hearing loss, middle ear hearing loss, ...). I think noice induced hearing loss is most common nowadays and is caused by structural damage to hair cells. Regenerating hair cells might cure this particular form of hearing loss but not others. I think the one you mentioned has a different root cause for which new hair cells are only part of the puzzle.
Be careful with these. My friend had to see a specialist after extended use of mynoise because it made his tinnitus much worse to the extent that it was almost intolerable.
Yeah, I tried them when they started and for me it didn't make my tinnitus worse, it just made me notice much more when it's there because suddenly I had breaks from it, and THAT was worse. I used them a few times and quit because of that.
There is this tapping on your head trick[0] that legitimately works for many people (me included) to clear up your tinitius but only for a few seconds after it. If you are curious what silence sounds you can try it.
I used to play in bands and go to a lot of concerts without earplugs (mistakes of youth). I’ve had tinnitus for almost 20 years, and I am so used to it now that it’s a non issue. That said, it drove me crazy in the beginning.
I used to play in bands and go to concerts without earplugs too, and one of my favorite pastimes is listening to music on loud volumes. Yet I've never developed tinnitus.
I guess I'm just lucky, or my hearing is just so sensitive that what I consider "loud" is actually fairly quiet. I know that I've had problems actually hearing sounds in band practice without using earplugs - I'd just hear a bunch of noise, and often lose the beat because of the inability to hear other musicians clearly.
30+ years of midwest raves did me in. One sound system had 1MW bass bins - have been to some with ~40ft x ~15ft of bass bins. Only one ruptured ear drum in all of that time (Regis - didn't even seem that loud) - that's the ear that is the worst. Doesn't bother me, other than anxiety about potential neurological effects.
Wait 30+ years of raves? In my mind’s eye you’re now a mulleted 45 yo Java dev at MedLab International creeping out the twenty something hotties, offering them glow sticks and Molly and telling them how you went to see Chemical Brothers before it was hip.
Have you ever been in one? I visited the one that Norwegian Broadcasting Corporation (NRK) had at Marienlyst in Oslo. This is before I knew anything about anechoic chambers and the sort.
It was called The Dead Room...
The first thing I noticed is that I had to speak a lot louder to be heard. But the most unnerving thing happened when we finally stood still in there.
I could hear my blood run through my own veins.......... So out of sheer panic I started moving and talking again lol.
This room was in the basement, and was secluded from all the other rooms in the building. The control room was even two stories up from the studio. They used it to record special samples that had to be completely "dead," as in no echo or reverberation on it outside the instrument itself. By they looks of it they also used it for Foley recordings, because there was some surfaces in there and some pans of powders and sand.
i worked for a company once with a large (10’ sided cube) and very high-quality anechoic chamber and would go in there on lunch breaks to mediate, was fantastic. (never had audio hallucinations.) i was young and had no hearing issues which probably helped.
My hearing is not particularly bad, and my tinnitus tends to come and go depending on the environment. Still, I would love to resolve it once and for all. It's a pretty common condition too.
Not obviously related to the article, but given this might attract the hearing-curious or knowledgeable.
For as long as I can remember I've had great difficulty hearing in noisy environments. In my younger years it didn't bother me too much as I was mostly at noisy events to enjoy the music anywhere, and if I wanted to talk we'd move somewhere quieter. If I make a concerted effort I can usually hear someone directly opposite me fine, though in an especially noisy venue like a concert I'm often filling in the blanks with lip reading or other visual cues. If I'm standing by something noisy in the house (range, operating vacuum cleaner, etc.) I can often tell someone is talking to me but usually have no idea what they are saying. All this has been on the "minor inconvenience" end of a personal impact spectrum. Recently I had a minor traffic accident (reversed into a car at very low speed, little damage and no injuries) and I realised that in that moment I had such little awareness of what was around me that it I was concerned. There was a lot of very loud conversation happening around me at the time. No screaming or anything, and I wasn't part of the conversation, but it was enough to completely destroy my focus at the time. I'd had a similar incident a couple of years prior. All this meant I decided I should book in to have my hearing checked.
Fast forward to the results: she said the tympanogram results show a highly compliant middle ear, but far more aggressively responsive than she'd seen before. Usually you'd see little or slow response if there was a problem but I'm the complete opposite of that. For the audiogram results I can hear into negative decibels but with a large enough delta in the results between left and right ear that I'll need to do some follow-up scans. She also ran two separate types of test to check for Auditory Processing Disorder.
Everything game back within range, or at least on the opposite side of what you'd call hearing "loss". Which prompted her to mention "but, at conferences lately they have been talking about a phenomenon that is presenting more frequently and being referred to as 'hidden hearing loss'...". So I've been down a rabbit hole of reading for the past week trying to filter out the things that a pure woo to the stuff that looks like it has some rigour to it. Seems like there's also been a trend for people to label some of these symptoms as "pub deaf".
I'm curious if any others on HN have had similar experiences and/or been down this research path before.
I got a job at a crowded and noisy casino. During some big events it was so crowded I had to walk sideways through crowds in the slot machine area. And very loud due to slot machines and people talking, yelling, screaming if they win.
Eventually I realized as I conversed with my co-workers we didn't need to yell and I could hear them 10 feet away. Note we did also use CB radios too but no mic just open speakers blasting which added to the noise.
I found out it is called the Cocktail Party Effect. It seems to be a learned skill that comes with time but it isn't something you naturally have. Ironically I probably now have hearing damage too working in that loud environment.
Interesting, I thought this was just a glitch of me. I think I have the same issue. Whereas other people seem to hear each other well in busy environments, it takes me much effort to focus and retrieve the person talking from all the other noise. The volume levels are fine, I'm just having trouble focusing and extracting the specific person I want to hear.
Now I also have some issue that eustachian tube gets a bit clogged up or something, because I react more than usual to small air particles. I can usually fix that by blowing while keeping my nose and mouth shut - but the issue above still remains in some form.
And how good do you hear in a silent environment? I'm asking because I feel a bit reflected in your description (always had problem following conversations in a noisy environment) but in a calm one I can hear very faint noises/voices (while others cannot, for example).
But TBH I don't know if my noisy envs experience is "normal" or it is just me.
I wouldn’t have thought I had anything beyond normal hearing in quiet environments. Modern life means there’s always some background hum of a refrigerator or an old light or a whining transformer in a wall or in a roof. But apparently I can hear negative decibels so maybe most people don’t hear these things?
If nothing else I’m finding the current journey interesting as I’m having to re-evaluate what is “normal” for both myself and others, for an experience that is obviously very personal and difficult to compare with others.
Yeah, they tested for APD (two different approaches). I found it really difficult though enjoyable in terms of being able to self analyse what it was that made me struggle. That said, my results were apparently normal and everyone finds it difficult.
I'm in the same situation. I was told that this is a relatively common symptom if you have ADHD and it's close to auditory processing disorder. Basically you just get deeply distracted by loud sounds and can't focus on anything auditory.
I had a similar inkling, which is what led me to discovering APD. The tests for that were normal though.
This whole “hidden hearing loss” concept seems like such a broad term for a huge group of things. Some of them potentially related to dysfunction in the inner ear that we can’t test for but can be treated (in mice) with neurotrophin.
The specialist I saw said at the last conference she attended the researcher presenting on it said most patients presenting were in their 40s. I’ve not seen any papers that make such a claim though. I was only the second patient she’d personally encountered that had the symptoms, and we are both in our 40s.
Yeah, I thought that might be it that too even though I don’t present any other autism symptoms. Much harder to diagnose in that case, which is why they tried to isolate with the APD testing.
This is incidentally one of the low-key issues that happens to a lot of soldiers - however attentive you are, ultimately you're going to get exposed to some loud bangs even if you're never in an actual war zone.
So there's a big demand for an effective way to restore damaged hearing.
And shooting enthusiasts. Decent ear pro significantly slows down the process, but it doesn't eliminate it. I'd love for my eye floaters and gradually-increasing tinnitus to be non-invasively curable (or at least treatable) before I die.
When I was younger I had a very expensive full blown audio system in my car. I would drive around blasting music so loud you'd feel it shaking your bones and punching your organs (don't worry it was a pretty rural area). A totally visceral experience.
I absolutely cannot do that anymore, given the damage it eventually did to my ears, but man, If I could heal my ears so I could go back and do that again...
I’m really tired and based on the headline I thought scientists had a cure for male pattern baldness and the new hairs increased your sense of hearing…
If you can regenerate hairs that stopped growing in one place, that sounds like a step toward regenerating other hairs that have stopped growing in other places.
And the market for baldness cures has got to be at least as big as the market for hearing recovery, despite the gulf in fundamental importance.
Big country, "louder is better", teens blasting their hearing with in-ears, concerts that leave your ears ringing for days, inadequate safety in the workplace, heavy use of drugs like Viagra (yes, hearing loss and tinnitus are a side effect in some users with high blood pressure). Diet-related hearing loss too as a lot of people eat crap. Probably other reasons too.
> heavy use of drugs like Viagra (yes, hearing loss and tinnitus are a side effect in some users with high blood pressure)
Oh wow. The Manga/Anime trope of male characters spontaneously bleeding from the nose when they get er... excited might actually have some real world examples.
Pretty sure "bleeding from the nose and ears" would kill the mood completely though. For most of the population anyway. ;)
Anecdote: Sudafed used to actually make my dad's nose bleed, but not just internally, from the external pores of the nose, and from the backs of his hands in terms of pores.
Depending on what you've lacked, for how long, your age—these are all variables. The younger you are, the lower the chances of reversing it as kids need a decent diet, period. How long you've been subsisting of off crap is the important one.
With all the above said, one of my born-blind friends has started going deaf due to bad diet, and whilst changing his diet hasn't improved his hearing, it has massively improved his overall health and importantly halted the hearing loss at the rate it was going, so it's not been a pointless exercise to make a lifestyle change that'll benefit him in the years to come.
Wishing anyone reading this good health for them and theirs.
Is this similar to the abandoned[1] program by Frequency Therapeutics?
> The FX 322 gel contains drugs that early studies indicate helped to aid new hair cell formation. These are called progenitor cells, which are unable to evolve into any body tissue. Instead, they are usually more inclined to develop
into cells near where they are found in the body.
> This particular drug encourages them to grow into stereocilia, which are hair-like cells in your ears that detect sound. Hearing loss is when these hair cells are irreversibly damaged, as they cannot repair themselves.
I actually suggested a friend to enroll in one sich study when it first surfaced in HN, a year ago.
My friend mentioned he didnt meet the criteria for the study (I think age was the problem).
I'm happy to see developments on this area of research and I hope someone succeeds. Being deaf is very difficult for a specially social animal like us, humans
Read (or skimmed) the article and I'm not an English native speaker but... TIL that "hair" can be used also for hearing related things? I thought that hair was just "any of the fine threadlike strands growing from the skin of humans, mammals, and some other animals."
The tiny sensors inside your ear are nerves attached to hair of various lengths. It's specialized, but it's recognizably the same thing as the kind on the outside of your body.
"Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment.[1]"
We have ultra fine hairs in our ears that wiggle when sound waves travel over them and those hairs bases are connected to receptors that capture those wiggles and send it to your brain. Thats (extremely roughly) how your ears work.
I have been curious lately if red light can cause hair growth externally, would it be something to research for internal "hair" growth. Getting light to the inner ear, would be difficult since it is encased in bone.
Why I feel uncomfortable when I hear: cells not dividing are now dividing that thanks to our drug cocktail. You know, if it cannot be stopped and they divide a bit to fast...
Wild guess: it is not actually what they managed to do.
> Despite the progress in our approach to achieve HC regeneration in the adult cochlea in vitro and in vivo, major challenges remain before potential clinical applications. First, regenerated HCs need to be terminally differentiated and fully mature, and to be located in the sensory epithelial region such that their stereocilia contact the tectorial membrane to mediate the mechanoelectrical transduction, as well as be able to survive long term. The current regenerated HC-like cells are immature and the time frame we used is not ideal to determine their long-term survival. One potential reason for the lack of terminal differentiation is the continuous Atoh1 expression mediated by adenovirus, which is known to impact HC maturation and is detrimental to HC survival (9, 56). Future studies to express Atoh1 transiently in the reprogrammed SCs could address the issue. Second, the surgical procedure of “cochleostomy” in the adult cochlea severely damages the microenvironment of the cochlea including extensive OHC death around the injection site. Future studies using an alternative delivery vehicle with a minimally invasive surgical procedure such as an AAV with round window injection could significantly improve HC regeneration efficiency without causing trauma to the inner ear. Third, major efforts should be made to identify/create new AAVs or novel delivery vehicles such as nanoparticles capable of targeting adult cochlear SCs for reprogramming. Finally, the restoration of hearing in adult deaf animal models significantly and reliably by HC regeneration will elevate the field of HC regeneration to a clinically relevant stage.
It sounds like the authors have found a more effective way to trigger generation of immature Hair Cells than was already known, but they're several large steps away from "restoration of hearing in adult deaf animal models".
However, the submitted article (from hms.harvard.edu) summarizes the findings as:
> [Authors] reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear.
While it's not outright false, the "successfully regenerated" isn't the way I'd interpret the PNAS paper. Perhaps I misread the paper.
[0] https://www.pnas.org/doi/10.1073/pnas.2215253120