Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Everyone here drooled over AM-101 and AUT00063 at the time. Hype was strong. Both failed.

Improving on earlier models is how you finally get it right.

I can't speak to AM-101 (which may just be an ill advised concept in general for anything not extremely acute), but I corresponded with one of the Autifony researchers and she is convinced the drug works, but is not specific enough (safer than Trobalt but a similar problem). They haven't given up on the drug at all btw and are still working on reformulation.

I can't think of one medical advancement they got right on the first try except for things that already occurred naturally (e.g., Penicillin). Imagine telling the Wright Brothers, their past failures meant they shouldn't believe in their eventual chances for success. Every improvement gets you closer.

Anyway, I get not wanting to "hype" things but when the science is there, there is reason for optimism.

I wasn't here when people drooled over AM-101, but I doubt I would have been one of them. If you look through my history, you will see that I was negative about:

Audion, Novartis and I hardly ever even visited the Lenire thread because the science was wishy washy and unclear to me.

I also think OTO-313 will be mostly useful acutely (with a few exceptions).

I think Neuralink is mostly hype (at least where it is anytime in the near future), too.

But I do think the science is absolutely there for FX-322 and OTO-413. Any problems that they have seem to be correctable formulation ones.

 

[Zugzug]

I don't know why everyone is freaking out that it won't work. It may not, but it just as well could. I understand the doom and gloom as much as the next guy, but it only takes one breakthrough and you're golden. Remember 10 years ago ALL scientists said it was impossible to fix sensorineural hearing loss. You now have seven or eight companies working on cure.

I was just reporting the Phase 1b results. How is that doom and gloom? It is a fact that they are using the same drug in Phase 2a. The difference is multiple doses, which is where all of the speculation is. I share your optimism that Frequency Therapeutics is the real deal. I don't share the optimism that the first formulation of FX-322 will put a total end to tinnitus, hyperacusis, profound hearing loss, mild to moderate hearing loss at all thresholds, etc.

 

[Diesel]

I'm practically salivating over the larger sample sizes. Good or bad, there should be a ton to infer from the Phase 2a results.

Yeah that sample size and the homogeneity of the participants at baseline. I suspect their "additional inclusion filter" ensured that participants had hearing loss that looked a lot like those responders in Phase 1/2 and that all were similar. Having 72 responders instead of 4 should drive that P-value down even in groups of 24.

 

[Jrblovsky]

I was just reporting the Phase 1b results. How is that doom and gloom? It is a fact that they are using the same drug in Phase 2a. The difference is multiple doses, which is where all of the speculation is. I share your optimism that Frequency Therapeutics is the real deal. I don't share the optimism that the first formulation of FX-322 will put a total end to tinnitus, hyperacusis, profound hearing loss, mild to moderate hearing loss at all thresholds, etc.

I don't believe that it will be a cure all either. I just don't understand why everyone is so hung up on Phase 1 data. I'm sure there will be at least marginal improvement regardless.

 

[Piney]

I have hope.

I just wish they could pinpoint why some with hearing loss have no tinnitus, and some do. That seems like the correct path.

I wish teams like the Bionics Institute who hopefully keep running these tests would team up with Frequency Therapeutics and Otonomy and roundtable some brainstorming.

I guess we will find out soon if FX-322 has legs.

 

[Zugzug]

I don't believe that it will be a cure all either. I just don't understand why everyone is so hung up on Phase 1 data. I'm sure there will be at least marginal improvement regardless.

I've recently read the paper thoroughly. You're right that it does look really promising. What I'm hung up on is the lack of statistically significant improvement at 8 kHz. As @Diesel pointed out, it could be that there's something special about the baseline levels that resulted in the strong improvements for some people.

Putting it all together, the WR, and WIN results are great. I think the tinnitus results will exceed expectations (which is extremely optimistic on a tinnitus forum).

I just can't see the same exact drug, but with 2 or 4 doses not only showing statistical significance at 8 kHz, but other lower frequencies as well.

I see an optimistic prediction being excellent EHF results and good reason to believe that reformulations or other methods will help lower frequencies in the pretty near future.

 

[Keith Handy]

I just can't see the same exact drug, but with 2 or 4 doses not only showing statistical significance at 8 kHz, but other lower frequencies as well.

I see an optimistic prediction being excellent EHF results and good reason to believe that reformulations or other methods will help lower frequencies in the pretty near future.

I don't think most people here are claiming any differently.

 

[scotty03874]

FX-322 is intended to treat Sensorineural Hearing Loss caused by Aging, Noise, Disease, and Ototoxic Medications.

So if you have nerve loss (hair cell) from a slap on the ear, you don't think FX-322 will help?

Every doctor has told me my hearing trauma is SSNHL? Not conductive loss.

 

[Diesel]

So if you have nerve loss (hair cell) from a slap on the ear, you don't think FX-322 will help?

Every doctor has told me my hearing trauma is SSNHL? Not conductive loss.

I would qualify a slap to the ear as an acoustic trauma, and therefore noise.

 

[FGG]

So if you have nerve loss (hair cell) from a slap on the ear, you don't think FX-322 will help?

Every doctor has told me my hearing trauma is SSNHL? Not conductive loss.

Assuming it's hair cell loss and you didn't somehow get a fistula from the force, there is nothing special about a slap as a cause that should cause problems.

My God would I be pissed if I got hearing loss from a slap, though...

 

[Orions Pain]

My God would I be pissed if I got hearing loss from a slap, though...

Halle Berry has 80% hearing loss in one ear and tinnitus from a domestic violence incident.

I do wonder how much physical damage vs. noise damage differs on the cellular level.

 

[serendipity1996]

Halle Berry has 80% hearing loss in one ear and tinnitus from a domestic violence incident.

I do wonder how much physical damage vs. noise damage differs on the cellular level.

This interests me too - I recall reading a patient story on the Hyperacusis Research website of a woman who got severe hyperacusis and tinnitus after being punched in the jaw.

 

[FGG]

This interests me too - I recall reading a patient story on the Hyperacusis Research website of a woman who got severe hyperacusis and tinnitus after being punched in the jaw.

Did she get traumatic TMJD from it? Severe tinnitus and hyperacusis are both linked to TMJ issues.

 

[throwaway]

Even if you don't have hearing loss, noise exposure can cause tinnitus, although researchers don't know exactly how. One theory was synapse damage. (Synapses are how nerve cells communicate with each other.) In rodents, loud noises can destroy synapses between inner hair cells and auditory nerve fibers, without causing hair cell loss or permanent hearing loss. The same effect might happen in people.

Source:
https://www.healthyhearing.com/report/53029-Tinnitus-and-hearing-loss

What if we only have synapse damage? FX-322 would be useless in that case. It sounds like synapses get damaged first before hair cells?

 

[FGG]

Source:
https://www.healthyhearing.com/report/53029-Tinnitus-and-hearing-loss

What if we only have synapse damage? FX-322 would be useless in that case. It sounds like synapses get damaged first before hair cells?

If you don't have hair cell loss, FX-322 isn't the drug for you. They are finding though that a lot of people who "only have synapse loss" in the lower frequencies, may have hair cell loss in the ultra high frequencies.

In general, synapses are more susceptible to noise damage, however, the hair cells closest to the base (higher frequencies) are also more susceptible to damage, they just aren't tested on a standard audiogram.

 

[serendipity1996]

Did she get traumatic TMJD from it? Severe tinnitus and hyperacusis are both linked to TMJ issues.

According to this, it was initially a dental injury and then the jaw pain spread to her ears, leading to tinnitus and hyperacusis. She was prescribed a mandibular splint to help realign her jaw, and then the pain spread to her neck, shoulder, and ears and she gets jaw spasms from noise.

Getting punched in jaw made every sound torture for this model

 

[Jrblovsky]

I feel like if you have a pressure wave go into your ear canal you could have a barotrauma or something along those lines. I don't know. I hope they release the data soon. I need to know what my future holds for me.

 

[Philip83]

Source:
https://www.healthyhearing.com/report/53029-Tinnitus-and-hearing-loss

What if we only have synapse damage? FX-322 would be useless in that case. It sounds like synapses get damaged first before hair cells?

It's not going to be a 100% perfect cure. But it's very unlikely that anyone with tinnitus or other hearing disabilities caused by noise trauma has NO hair cell loss, so there should be some rate of improvement for basically everyone if I have to guess.

 

[Jrblovsky]

Everyone here drooled over AM-101 and AUT00063 at the time. Hype was strong. Both failed.

Great. The Dems also said Trump would never make it into the White House. Somehow that still happened. Lots of drugs fail clinical trials. If it doesn't work then oh well I guess. Eventually there will be a breakthrough in the field. The body can heal. Someone will figure it out.

 

[jeff W]

You're right. I've met several of them and am blown away how stupid they are. Most of them are good for nothing more than doing a hearing test and fitting hearing aids. Hopefully drugs will eliminate this useless field of medicine soon enough.

 

[Diesel]

Source:
https://www.healthyhearing.com/report/53029-Tinnitus-and-hearing-loss

What if we only have synapse damage? FX-322 would be useless in that case. It sounds like synapses get damaged first before hair cells?

Most of the current research points to NIHL/SNHL being a combination of both synapse loss AND hair cell loss. So, FX-322 will still take care of wherever hair cells are missing... just for reference:

 

[GBB]

Here's my theory/hope: your brain only produces tinnitus in the synapse damage scenario when we cross a threshold of damage, otherwise all of us here would have had tinnitus much sooner - clearly we had to work up to it. We also probably have some hair cell damage; when hair cells are repaired by FX-322 they grow new synapses. Therefore repairing hair cells may repopulate damaged synapses, and consequently ameliorate your condition regardless.

 

[Pharz]

If there was to be a Phase 3 trial, does anyone know if they recruit participants from Europe? Or should I travel to US to participate in the trial?

 

[serendipity1996]

Here's my theory/hope: your brain only produces tinnitus in the synapse damage scenario when we cross a threshold of damage, otherwise all of us here would have had tinnitus much sooner - clearly we had to work up to it. We also probably have some hair cell damage; when hair cells are repaired by FX-322 they grow new synapses. Therefore repairing hair cells may repopulate damaged synapses, and consequently ameliorate your condition regardless.

It seems like synapse loss is far more easily triggered in that you can lose a significant number of them before it shows up on an audiogram. I reckon those of us with enough damage to trigger tinnitus and hyperacusis have extended high-frequency hair cell loss too - I would be very surprised if not.

 

[Jrblovsky]

Here's my theory/hope: your brain only produces tinnitus in the synapse damage scenario when we cross a threshold of damage, otherwise all of us here would have had tinnitus much sooner - clearly we had to work up to it. We also probably have some hair cell damage; when hair cells are repaired by FX-322 they grow new synapses. Therefore repairing hair cells may repopulate damaged synapses, and consequently ameliorate your condition regardless.

Your theory is absolutely correct. I'm 100% convinced the changes researchers see in the brain is from lack of neural input. The nerve is not supplying the brain with an input that it is programmed to have. It's like a body control module in a vehicle or a PLC setup in a machine. Each signal in millivolts triggers something specific. If the theory of plasticity is true which I can promise you it is, there is no reason the brain will not forget the noises it's generating when the inputs are restored. It's a basic root cause analysis. I'm damn close to a PhD on my academic career but fuck, this is basic undergraduate material in electrical engineering. It blows me away how far behind the medical field is modern engineering. If nobody challenges the status quo these lame doctors will never push to help anyone.

 

[FGG]

According to this, it was initially a dental injury and then the jaw pain spread to her ears, leading to tinnitus and hyperacusis. She was prescribed a mandibular splint to help realign her jaw, and then the pain spread to her neck, shoulder, and ears and she gets jaw spasms from noise.

Getting punched in jaw made every sound torture for this model

I really wish I didn't read this. It's so sad and infuriating. She clearly has luxated her jaw (second photo) and insurance fought with her for 5 months (!) before they would approve treatment (the delay certainly promoted very abnormal healing) and on top of that made her go to a doctor 50 miles away when she couldn't even handle 15 dB of noise. That poor woman .

 

[throwaway]

If hyperacusis has to do with hair cells or synapses, why do some people's hyperacusis completely vanish?

 

[FGG]

If hyperacusis has to do with hair cells or synapses, why do some people's hyperacusis completely vanish?

Hyperacusis seems to have a variety of causes like tinnitus.

Regardless, if you are talking about loudness hyperacusis for cochlear causes, the theory is the brain turns up the central gain in response to injury and this can normalize with time.

Middle ear disease can also cause hyperacusis. Such as with abnormal Stapedius Muscle dampening.

If you are looking for one structure or condition to cause either tinnitus or hyperacusis, you will find it can't be explained that way.

 

[Diesel]

If hyperacusis has to do with hair cells or synapses, why do some people's hyperacusis completely vanish?

Oh boy...

 

[Jrblovsky]

If hyperacusis has to do with hair cells or synapses, why do some people's hyperacusis completely vanish?

Good question. I had hyperacusis bad after what happened to me and it went away after 90 days or so. I wish the same had happened for the tinnitus.