Frequency Therapeutics — FX-345

But never any mention about it helping for tinnitus. Please tell me that it might.

 

Well, I cannot currently say yes or no to this. Reason being this is truly a historical moment in medicine; this treatment will be the first time ever that hair cells have been restored in the ear.

If you want me to postulate some just based on what we know about the ear, I would say yes, this should help with tinnitus. Typically, when the hair cells in the ear are blown over, tinnitus occurs; then when they self-correct, the perception of tinnitus recedes. This drug could therefore hypothetically completely eliminate some people's perception of tinnitus, but the real truth is we have no idea because this has never occurred before in human history. Maybe if one of our fellow forum users knows a little bit about avian anatomy, we might get some answers as birds are capable of such regeneration without fancy biomedical startups.

Overall, I think hearing health is about to see quite a bit of a boom in regard to medical advances. Doctorate students are running out of reasons to continue studying other aliments because most of them have solutions and treatment modalities already available. Resulting in highly specialized research efforts that might not garner much attention such as formulating a drug that reduces hair loss caused by cancer treatment. This is great, but did you hear about that one guy who cured hearing loss?

FX-345 is promising due to its predecessors' success at the clinical trial phase; bear in mind that not everyone was a super responder to a prototype drug. BUT there were responders... this is some of the best news modern medicine has gotten in a while.

 

That is a very good point. I guess many of us have experienced temporary tinnitus when our ears have been exposed to loud sounds such as a night out at a club or something with similar sound levels and later on, after the ears have gotten some rest, the tinnitus has gone away.

More promising research news:

"The images clearly showed that the hair cell bundles were in accordance to what is observed on inner hair cells during development. Further studies showed that these cells also had some characteristics that suggested that they were capable of sensing sound."​

Molecular Barriers to Overcome for Hair Cell Regeneration in the Adult Mouse Cochlea

What an uptick in quality of life it will be for people when we can regenerate hearing and get rid of any tinnitus. And also an uptick for the music and Hi-Fi industry who will likely get many more customers.

 

A historical moment in deception, yes. It's called stacking the deck; if you are afflicted by any one out of a large number of troubling conditions, you are very likely to consider the next decade or so a historical moment in medicine.

 

I'll sound pessimistic, but it's shown that stuff that fixes mice ears doesn't translate well to human ears. I personally lost any interest in such articles discussing success with mice, as in all cases so far, the medicine didn't work for humans at all (FX-322 failed, OTO-313 failed, PIPE-505 failed etc).

 

I'm not sure where you're going with this, would you rather them go ahead and put a nail in the coffin on these projects? Deception of what exactly? This decade alone has brought our understanding of the ear and brain closer to meaningful clinical practices than the past 60 years has.

There are only so many researchers and so much money to go around unfortunately; to discredit meaningful scientific progress that mind you, in relative terms is moving at light speed is disingenuous. The work being done on tinnitus is directly translatable to other ailments; with just one example being scientists are developing advanced imaging techniques to observe a specific brain function such as tinnitus. Neuroscience is interdisciplinary and even one small advancement moves the entire field forward, improving the quality of life for more than just us.

The perfect example is Frequency Therapeutics' long term goals of developing a MS drug. The research they are doing to find a resolution to hearing loss will directly transfer to their other long-term goals of repairing damaged myelin sheaths through cellular therapy.

Truthfully, I'm not sure what you want. Would you just like us to stop trying and give it a rest?

 

@CarlosEstan, I think it's called frustration which is understandable. I'm what you would call pessimistic about Frequency Therapeutics, because I cannot stand the ethos of biotechs and stock markets. Maybe that's me and being a UK citizen. People on here have been stung with misleading data and statements. I much prefer universities, who operate differently. As it happens, Michigan University is where the first tinnitus treatment has come from.

Are you a new member perhaps?

 

You ignore evidence of all the parallel medical progress going on for many, many other ailments and diseases. There is going to be so many revolutionary medical developments in the next decade and after, that to single out one of them (particularly one which happens to address your own demographic, tinnitus sufferers etc) as something very unique, you have to pretty deceived by your own circumstance. A spinal cord injury patient as tunnel-minded as you might consider the next few years as truly historical. A HIV patient might respectively consider the next few years as truly historical. There's a good chance that the same would apply to depression, diabetes, Alzheimer's disease, various cancers, herpes & zoster, teeth, skin, hair, neurons, whatever. You and @Nick47 got the wrong idea if you think I was being a pessimist.

 

I posted this concern to the researcher Amrita who responded:

“You are right. Several medicines that are shown to work in mice do not work in humans. As far as gene therapy is concerned my work above is a very small piece of a large puzzle. The remaining pieces will explore regeneration of varied aspects required to re-establish the entire hearing architecture (the sensory neurons, the membranes etc.). The hope is such a re-establishment will address the hearing loss problem a lot better than what’s available now.”​

So piece by piece we seem to be getting there. But I sure get the impression there is some time left before it happens.

 

Well we can say with a fair degree of confidence that tinnitus will be treated before hearing loss is restored. Easier to treat a disease than to grow something that naturally doesn't regenerate!

I will take the tinnitus treatment above the latter. Most here would!

 

I envy the youth of Tomorrow who will simply need a trip to a regenerative surgeon to restore hearing, like seeing a dentist for a toothache. Regenerative medicine is a very real possibility for a future profession. Whether or not FREQ will pioneer a successful early version of the practice is still uncertain.

 

*Easier to treat a symptom.

 

Well yes, I used to see it as a symptom but now, after recent findings, I'm not sure. After Susan Shore's findings and treatment inducing long-term plasticity, I don't know? Is increased firing in the DCN a symptom or disease in itself? In other words, is malfunctioning in the DCN the disease and tinnitus the symptom?

 

I would not say it's accurate to say FX-322 "does not work" in humans. Firstly, it is shown that the treatment only penetrates the cochlea to cells responsible for transduction from 12 - 20 kHz. There is very little (well, less) 'important' spectral content at those frequencies for humans, especially when it pertains to speech. With regards to speech, past 12 kHz, you are mainly dealing with lower amplitude harmonics of upper-frequency consonant sounds like "f," "th," "s". One thing to note, is virtually all adults past the age of 30-40 already have some significant hearing loss past 12 kHz anyway, meaning that "normal adult" hearing in those regions is already damaged to a certain extent yet normal adults usually don't have any issues with intelligibility, chronic tinnitus etc.

The Frequency Therapeutics studies did show statistical improvements in speech intelligibility, which was virtually the only thing tested and is almost certainly what was to be expected due to the limited bandwidth of what the treatment targets and what that would translate to in terms of audibility. Those that do not really understand the implications of these reported outcomes lost confidence in the company, which was evidenced by the stock tumbling and people claiming it did not restore hearing. As a medical and drug researcher, musician and avid audiophile, I find the "poor" results of FX-322 and Frequency Therapeutics as a whole still very hopeful. FX-345 is expected to penetrate deep enough to treat 4 kHz - 20 kHz, which not only encompasses the region treated by FX-322 but also the significantly more important audiometric region of 4-8 kHz, which I believe would be optimistically predicted to show significant improvement 99%+ of hearing loss cases. Being able to treat tinnitus itself is perhaps not as guaranteed, but most cases of tinnitus are a result or at least highly correlated with some sort of measurable hearing losses or damage, so I don't doubt that a restoration of hearing combined with time for the plasticity of the brain to do its thing will help a massive amount of people, especially those that are on the younger side.

Personally, a majority of my hearing loss and the frequency of my tinnitus is contained in the midrange at 500-1500 Hz, which is probably the worst place anyone could hope to experience a narrower-band loss. It also means that as it stands, both FX-322 and FX-345 will do very little for me since my damage is under 4 kHz. Despite this, I've still invested quite a bit of money into the company, because even if it does not help me, I am that confident in its success. If outcomes of FX-345 are a success audiometrically, I'm confident the company will probably explode overnight and it is very likely a further formulation to treat the whole cochlea will be developed.

 

@perfectpitch, some valid points but perhaps overly optimistic for sure. Welcome to the forum and congrats for your first post!

 

I don't disagree with the points you raised. Maybe it was the trial design that was to blame for the first failed Phase 2 (I think?) of FX-322. I'm still curious why they keep insisting on speech intelligibility. I know how frequencies work, being a music producer for over a decade, and I too agree that the 12 kHz and upwards range is generally important because there lies the "brightness" or "air" of sounds. But, I still can't see how that range helps speech so much because only the upper part of "f, th, s, k etc" lies above 12 kHz. Just take an audio spectrum analyser and you'll see that the 10 kHz+ regions light up very very rarely during normal speech.

I'm just saying here that maybe what is to blame, is the absence of more efficient and reliable tests to measure what FX-322 (or similar drugs) really do. Speech recognition just seems way too subjective to show the truth.

I wish every day that these drugs will finally work and help all the people who need them. But so far, there's only disappointments one after another, unfortunately.

For the record, I also have my tinnitus mostly at 1 kHz - 2 kHz range (plus a higher frequency white noise hiss), and a mysterious -25 dB notch at 2 kHz in left ear. Otherwise, normal hearing till 15 kHz (29 years old). So, yeah I'm sort of in the same category of lower range too.

 

Here is my audiogram. Do you think I could benefit from either FX-322 or FX-345?

And why wouldn't these treatments be able to treat your type of hearing loss? I thought FX-345 could penetrate deeper? Please educate me.

 

Your audiogram is pretty normal, just a slight noise notch at 4000 - 6000 Hz. Most ENTs don't even consider this to be a hearing loss of any magnitude. You shouldn't have any trouble hearing in noisy settings. Your tinnitus could be from upper cervical issues, TMJ, Eustachian tube disorders or many other possible things. Probably just from noise exposure.

I had -45 dB @ 4000 hz in both ears before my acoustic trauma on my right ear, with no tinnitus at all. If your word recognition score is close to 100%, which I'm guessing it is, don't waste your money on a treatment like Dr. Shim's protocol. Maybe try LLLT, that could possibly help high frequency hearing loss. It changed mine +15 dB for the better in both ears based on my audiograms. If FX-322/FX-345 is available in the future, it wouldn't hurt to try it. Nobody knows if it could help you right now. I believe some patients showed only slight improvements @ 8000 Hz only in a prior study phases.

I would kill for your audiogram...

Is your tinnitus only in your left ear? A TV/music on should mask your tinnitus...

 

Are you still able to work on music?

 

Yeah, thankfully with no problem. My tinnitus is generally mild, although it has its moderate bad day once or twice a week. It seems it isn't affected by external noise (it was a bit only for the first month when I got it). But I only produce music at my home studio, where I have all volumes controlled and I don't use headphones at all, only studio monitors.

I don't believe my -25 dB hearing loss notch (or any other hidden hearing loss) has affected my producing and mixing, since the feedback from people is good for my music and stuff. So yeah, I keep doing it because it's the only thing that really brings me some joy. It is also a great activity to take the mind off the tinnitus on the bad days...

 

FX-322 apparently only goes deep enough to target 12+ kHz and FX-345 supposedly only goes deep enough to target 4+ kHz, so since my losses are at 0.5-2.5 kHz (under 4 kHz) I would not expect either of them to help me as-is. I don't have broad high-frequency age-related hearing loss, I have specific notches of loss only contained to those regions which is not that common. My higher frequency hearing is fine (actually excellent for my age), so I would likely not get any results because the treatment doesn't penetrate deep enough to treat my specific losses, at least according to the company. If or when they "update" the treatment to penetrate further, perhaps then it would help me.

Your hearing appears to be relatively "normal" in the right and you have losses from ~2.5-8 kHz in your left. The fact that it goes back "up" after 6 kHz means it too appears you have a notch, so there is a decent probability your hearing beyond 8 kHz is perhaps OK (although not necessarily so) and not typical of progressive age-related loss. FX-345 (not FX-322) would potentially be the one you would want to try theoretically, since at least it would cover the 4-8 kHz region of your loss which you know exists from the audiogram, and any other potential unknown high frequency loss. You would still likely have problems from ~2.5-4 kHz though if the claims about the penetration range of FX-345 are true. Of course, none of that is medical advice, it is just a logical assessment based on the claims and the results of the company

Yes, I think the trial design was probably a significant hurdle. I initially wondered why they didn't do something more objective like tone audiometry, although to be fair from what I have read there is a big problem with high frequency audiometry (8-16 kHz) in that there are limited standards, is very hard to determine individual baselines due to wide variances in hearing loss even in "normal" individuals (occupational risk being a big factor) and also equal-loudness determination in humans also has higher variance at very high and low frequencies and can also be affected moreso by neurological adaptation. So high frequency audiograms are not typically produced for those reasons, especially if you factor in that it takes more time to do on top of being troublesome. Most hearing aids and their amplification algorithms are also limited to amplify up to 10 kHz as well, so even for individuals seeking treatment for a loss normally it does not practically give the clinician any information they can use in treatment. Establishing those tests for many individuals takes a lot of time (and thus money) and does not necessarily return accurate results which could be a big reason for exclusion in an early part of a study. There is also a concept of "hidden" hearing loss in which many patients may have relatively routine audiograms but have significantly impaired hearing in terms of intelligibility or speech-in-noise caused by other mechanisms of damage not explained by the audiogram. I guess their approach was that even low levels of HF has been shown to affect things like speech intelligibility or speech localisation, and that positive changes to a broad spectrum would change the timbre of speech or aid in processing enough for subjects to score statistically better on standard speech tests. That in theory would have been enough to greenlight further development i.e. FX-345 and so on.

 

Thanks for answering my question. My tinnitus doesn't really bother me so much, but I've developed a weird thing called palinacousis, it's triggered by loud bassy music. My left ear is acting up again with strange sound coming out of it, I don't know if I can attribute the mild hearing loss on my left ear to either Viagra or an ear infection, but honestly it's probably noise induced because I always had headphones on me.

What is LLLT? Do you think it could help my mild hearing loss on my left ear?

It seems FX-345 could potentially help me. I wonder, if it ends up on the market, if some responders could heal even more than others. I'm thinking that profound hearing loss probably won't be treated for the remainder of this decade, but most should have some gain from this that will allow them to get some normalcy back.

What do you think? Are there any other companies that could help us? I don't think Otonomy has too much longer but hopefully big pharma will pick up their research. Let me know if there's more companies trying to regenerate hearing.

 

@Chad Lawton, I have attached my audiogram above. Do you think FX-345 could help me? What are your thoughts on Viagra and hearing loss?

 

LLLT is low-level laser therapy. You can have it done in Sarasota, FL. It helped me a lot in September 2020 when I had it done there. 15 sessions of clinical laser.

 

Just to play devil’s advocate with this, universities are not infallible either. More often than not, they put far too much focus on getting a publication because that can generate additional funding, rather than focussing on their mission statement of a treatment/cure or the foundations of understanding how to make one for conditions. Publications in academia are seen as a badge of honour, whereas in industry, they’re mostly seen as a waste of time. Unless you’ve been through the peer reviewed process of a publication, you might not know it’s not this iron clad review that people make out. You provide the data you want the reviewers to see, nothing more. Regulatory body reviews are far more strict.

A lot of university funding comes from private companies. My company fund a lot of university work. Either because we do not have the capacity to investigate it ourselves, or because a university may specialise in a specific area of study.

Numerous times we have to realign the university back onto the original mission because they tend to get bogged down with ‘we found this out so started looking at it too because it’s quite interesting.’ Interesting wasn’t the scope of the funding. The basis/foundations for a pathway to a cure/treatment was and you’ve gone off on a tangent.

Of course it does go both ways. But a romanticised view of ‘university good, industry bad’ isn’t the whole picture.

 

I suspect there is going to be a whole lot of formerly deaf mice running around with perfect hearing before we get our hearing fixed

 

I second that motion...

 

Looks like you may benefit from FX-345 based on where your notch is and if FX-345 penetrates as deeply as they are predicting. As for Viagra & hearing loss, I can't say I know anything about it.

 

Thanks for this. I recently had another ear infection, one in June last year and another one December 26. I'm hoping I haven't done further damage to my hearing because of it, as my left ear still feels full and hurts, but I do have mild TMJ and maybe that's what it is. I hope brain plasticity allows for the new hair cells to reconnect and regain some hearing back.

So many people now have hearing loss because of COVID-19, something needs to happen fast and big pharma knows this. I do think we'll have effective treatments and I'm hoping FX-345 is one of them. Thanks for explaining this to me.

 

It actually boggles my mind that this is a relatively minor area of study. You're born with your hair cells, if they die, that's it. Kaput.

With how easily our hearing is damaged; be it from spending an hour in a live music bar or from firing a rifle once, I cannot comprehend that this isn't a hugely more advanced area of study for pharma/biotech companies. They'd make trillions off it within a few years if they developed a successful way to regenerate hearing. I'm very surprised at the US Gov, as the veteran claims for tinnitus go into the billions of $ a year.

Here's hoping that 1 successful, even semi-successful drug kick-starts a hearing regeneration arms-race and within the next 15-20 years it's a routine procedure.