Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Sorry but what do you mean? Is it something good?

I just mean that everyday sounds will help the brain readjust to normal input again.

 

[serendipity1996]

I am suspicious of this site and article. It is very commercially motivated.

The problem I have with this and other articles like this on this site is they are using "science" to sell. So, in this case, blurring the lines between being informative and using what they've derived as research data to get you to buy hearing aids. Healthy Hearing partners with Your Hearing Network, a health plan administrator. Which, in turn works with select partner clinics. The end goal for these sites is to bend science with their content to get you to take action: contact a clinic, consider buying hearing aids.

The only people that really knows the answer to your question at this point are Frequency, the patients that have benefitted from FX-322, and their doctors.

Speaking anecdotally, I think the brain and auditory system will start picking up the new sounds from the sensory cells as intended and process as normal. In terms of understanding conversations from improved hearing, I think the results would be pretty immediate.

This is really reassuring. To be honest, I think at this point I am just coming up with esoteric "what-if" scenarios in my head and getting carried away with anxiety!

 

[Diesel]

This is really reassuring. To be honest, I think at this point I am just coming up with esoteric "what-if" scenarios in my head and getting carried away with anxiety!

Yeah, I totally acknowledge that. I also think that if people had some really extreme reaction to their hearing sensors being regenerated, it would have been considered an adverse reaction in the Phase 1/2. Also, considering Frequency is looking at quality of life measures as Secondary Outcomes in the Phase 2A, (HHI, HSI) it stands to reason that they are hypothesizing that QOL increases correlate with positive hearing outcomes.

 

[FGG]

Yeah, I totally acknowledge that. I also think that if people had some really extreme reaction to their hearing sensors being regenerated, it would have been considered an adverse reaction in the Phase 1/2. Also, considering Frequency is looking at quality of life measures as Secondary Outcomes in the Phase 2A, (HHI, HSI) it stands to reason that they are hypothesizing that QOL increases correlate with positive hearing outcomes.

Not only that but word scores would not have increased if the brain couldn't readjust.

 

[serendipity1996]

Yeah, I totally acknowledge that. I also think that if people had some really extreme reaction to their hearing sensors being regenerated, it would have been considered an adverse reaction in the Phase 1/2. Also, considering Frequency is looking at quality of life measures as Secondary Outcomes in the Phase 2A, (HHI, HSI) it stands to reason that they are hypothesizing that QOL increases correlate with positive hearing outcomes.

True and I think it's very easy with the internet to go seeking out information which aligns with your obscure anxiety-driven scenario. But this is actually quite unlikely and we should focus on the clinical outcomes e.g Frequency's results which so far seem to bode well.

 

[ASilverLight]

Our brains may be very bad at dealing with missing signals and properly channelling everything, but I do believe that once these are restored and calmed down our brain will adapt to it with no trouble. We already have similar outcome from hearing aids and cochlear implants so I don't think there is too much to worry about.

Just my take though.

Also I saw this mentioned before, but I have read a lot of reports of people on Twitter stating they had COVID-19 and now deal with a ringing in their ears (be it due to medication they received or other things).

As COVID-19 is such a big thing, maybe it'll get us more help.

 

[Diesel]

Our brains may be very bad at dealing with missing signals and properly channelling everything, but I do believe that once these are restored and calmed down our brain will adapt to it with no trouble. We already have similar outcome from hearing aids and cochlear implants so I don't think there is too much to worry about.

Just my take though.

Also I saw this mentioned before, but I have read a lot of reports of people on Twitter stating they had COVID-19 and now deal with a ringing in their ears (be it due to medication they received or other things).

As COVID-19 is such a big thing, maybe it'll get us more help.

It's interesting you mention the correlation between COVID-19 infections and hearing loss. So far it looks like the research is relatively inconclusive with some broad correlations presented, but it is early. It does seem like many of the folks who had been infected by the virus have a long road to recovery. Once infection rates begin to finally drop, perhaps after a reliable vaccine/treatment is available; I imagine focus will shift to caring for the millions of people who were unable to fully recover without needing on-going treatment/care.

If hearing loss/tinnitus becomes prevalent enough, perhaps it will bring some new light to the disorder that we live with every day. The outcomes may vary. It may trigger the governing bodies in play to bend clinical trial rules or treatment access to help those recovering become whole again. It may bring more public awareness to the work that Frequency is doing, and increase participation in their trials. It may just drive the stock up. Hard to say.

 

[ActorFred]

It's interesting you mention the correlation between COVID-19 infections and hearing loss. So far it looks like the research is relatively inconclusive with some broad correlations presented, but it is early. It does seem like many of the folks who had been infected by the virus have a long road to recovery. Once infection rates begin to finally drop, perhaps after a reliable vaccine/treatment is available; I imagine focus will shift to caring for the millions of people who were unable to fully recover without needing on-going treatment/care.

If hearing loss/tinnitus becomes prevalent enough, perhaps it will bring some new light to the disorder that we live with every day. The outcomes may vary. It may trigger the governing bodies in play to bend clinical trial rules or treatment access to help those recovering become whole again. It may bring more public awareness to the work that Frequency is doing, and increase participation in their trials. It may just drive the stock up. Hard to say.

Regarding COVID-19 and hearing loss there is some evidence that COVID-19 in some cases causes hearing loss. The evidence is of poor quality though.

https://www.manchester.ac.uk/discov...nvestigating-the-long-term-impact-on-hearing/

 

[ASilverLight]

@Diesel @ActorFred

Yeah, I didn't really find much research, just people talking about it online. Which isn't any clear evidence, but the moer people talk about it, especially in the aftermath of having COVID-19... the more chances we have at it being taken seriously, even just slightly so.

It's too early to tell though.

 

[tommyd87]

This is something that kind of intrigues/worries me. We know that hearing loss is associated with cognitive decline and that the sooner hearing loss is treated the better, e.g. people tending to have greater success with hearing aids the earlier they seek treatment as the hearing centers of the brain weaken over time. Would someone with longstanding hearing loss who gets treated with, say, one of the regeneration drugs also require some sort of sound recognition therapy as your brain adjusts to the renewed input?

I could be completely off-base here and and am just going by what I read here: https://www.healthyhearing.com/report/46306-Hearing-loss-auditory-deprivation

Bingo. I would say someone's spot on here, hence why we see cochlear implant individuals needing to learn sounds again after getting it. It isn't difficult although absolutely it will be an obvious part of it.

 

[Jurger]

Bingo. I would say someone's spot on here, hence why we see cochlear implant individuals needing to learn sounds again after getting it. It isn't difficult although absolutely it will be an obvious part of it.

It depends on what is atrophied with sound deprivation. The brain part won't be helped with therapeutics. If the hair cells, spiral ganglion neurons or synapses atrophy, therapeutics could (partially) fix that. Maybe the brain readjusts after restoration.

 

[Diesel]

It depends on what is atrophied with sound deprivation. The brain part won't be helped with therapeutics. If the hair cells, spiral ganglion neurons or synapses atrophy, therapeutics could (partially) fix that. Maybe the brain readjusts after restoration.

The brain clearly readjusts after restoration without any intervention. As @FGG mentioned a few posts ago, how else would word recognition scores improve over the 90-day timeframe of the Phase 1/2. In no way did Frequency do any other retraining/therapy during the Phase 1/2 with these patients after FX-322 was applied. All they did was sit them in the sound booth and do another round of word recognition testing.

FX-322 did its thing, new cells grew and connected to the nerve, and the brain responded as mother-nature intended.

Sometimes it's just that simple.

 

[tommyd87]

The brain clearly readjusts after restoration without any intervention. As @FGG mentioned a few posts ago, how else would word recognition scores improve over the 90-day timeframe of the Phase 1/2. In no way did Frequency do any other retraining/therapy during the Phase 1/2 with these patients after FX-322 was applied. All they did was sit them in the sound booth and do another round of word recognition testing.

FX-322 did its thing, new cells grew and connected to the nerve, and the brain responded as mother-nature intended.

Sometimes it's just that simple.

Bingo. It is the sheer lack of auditory stimulation which leads to the issues related to atrophy which will not be present when restoration has happened.

 

[RODRIGO]

We are all looking forward to the FX-322 results...

I have some questions, and I would like to know what you think:

1. How many decibels do you think you can recover from hearing loss?
2. Will you regain hearing at the level of a healthy teenager?
3. It appears that low frequencies will not be recoverable. For which frequencies will FX-322 be effective?
4. Will very high frequencies from 8000 Hz recover up to 20,000 Hz?
5. Will it be more effective with major hearing loss or minor hearing loss?
6. Many people with hearing aids say that their tinnitus decreases a lot with the hearing aids... do you expect the same to happen with FX-322?

Thank you very much.

 

[Sloth]

How many decibels do you think you can recover from hearing loss?

In theory you should be able to fully recover. However, that depends on your ear still having functioning support cells.
Without support cells the affected areas can't recover. You'd need to be at least profoundly deaf for that to happen though.
We will see the limits of FX-322 after their phase 2a ends.

Will you regain hearing at the level of a healthy teenager?

I'd say even better because most teens are already damaging their hearing on a daily basis.

It appears that low frequencies will not be recoverable. For which frequencies will FX-322 be effective?

They are recoverable. There is no functional difference between the cells in low and high frequency areas. However, low frequencies are deeper in the cochlea and therefore more difficult to reach.
They are already working on a gel to deliver it deeper into the cochlea.

Will very high frequencies from 8000 Hz recover up to 20,000 Hz?

Those are the most affected by FX-322.They are (at least with the current formula) the main frequencies that will recover.

Will it be more effective with major hearing loss or minor hearing loss?

Doesn't matter. People with major hearing loss will obviously benefit the most from it but in the end all that matters is whether you still have supporting cells.

Many people with hearing aids say that their tinnitus decreases a lot with the hearing aids... do you expect the same to happen with FX-322?

That's our hope and expectation. Otherwise we wouldn't discuss a hearing restoration medication on a tinnitus forum (or maybe not that much).
It's pretty clear that for most people tinnitus is a symptom of hearing loss so it's reasonable to assume that by repairing the underlying damage the symptoms should go too.
But we will have definite answers once Frequency Therapeutics releases their phase 2a data since they are measuring tinnitus as a secondary outcome.

 

[FGG]

In theory you should be able to fully recover. However, that depends on your ear still having functioning support cells.
Without support cells the affected areas can't recover. You'd need to be at least profoundly deaf for that to happen though.
We will see the limits of FX-322 after their phase 2a ends.

I'd say even better because most teens are already damaging their hearing on a daily basis.

They are recoverable. There is no functional difference between the cells in low and high frequency areas. However, low frequencies are deeper in the cochlea and therefore more difficult to reach.
They are already working on a gel to deliver it deeper into the cochlea.

Those are the most affected by FX-322.They are (at least with the current formula) the main frequencies that will recover.

Doesn't matter. People with major hearing loss will obviously benefit the most from it but in the end all that matters is whether you still have supporting cells.

That's our hope and expectation. Otherwise we wouldn't discuss a hearing restoration medication on a tinnitus forum (or maybe not that much).
It's pretty clear that for most people tinnitus is a symptom of hearing loss so it's reasonable to assume that by repairing the underlying damage the symptoms should go too.
But we will have definite answers once Frequency Therapeutics releases their phase 2a data since they are measuring tinnitus as a secondary outcome.

Just want to add that "they are working on a gel to penetrate further" is logical speculation based on their job postings. They haven't issued a statement on this. However, there is a huge market for especially the full speech range so I can't imagine they don't have some sort of plan past approval of the first formulation.

There are also companies that are working on increased delivery with other methods: e.g. nanoparticles, Otomagnetics, ultrasound microbubbles, surgical approaches (this is mainly for AAV drugs but things like canalostomy could theoretically be used for this too) etc.

 

[tommyd87]

We are all looking forward to the FX-332 results...

I have some questions, and I would like to know what you think:

1. How many decibels do you think you can recover from hearing loss?
2. Will you regain hearing at the level of a healthy teenager?
3. It appears that low frequencies will not be recoverable. For which frequencies will FX-332 be effective?
4. Will very high frequencies from 8000 Hz recover up to 20,000 Hz?
5. Will it be more effective with major hearing loss or minor hearing loss?
6. Many people with hearing aids say that their tinnitus decreases a lot with the hearing aids... do you expect the same to happen with FX-322?

Thank you very much.

It should also be commented that although the gel doesn't get to the low frequencies yet from what we were informed about in the first trial, there are multiple dosing tests being done now which are measuring the effects of this.

The first trial was a double blind trial where they put diferent doses randomly in the ear of the candidate. All ee know is the four that got injected and actually showed improvement were likely to have been done with the larger dose due to the fact this has been used in the latest trials.

Thus there is a good chance based off the evidence that more doses results in more improvement based off the info in the first trial. thus this may even lead to the treatment working further in the ear as it is possible that the drug treats this damage which is likely to be greater then proceeds further in the ear.

I am pretty sure freq dont even know completely how their product works other than to say simply that it does based on the outcomes of the first trial since they were limited to one dose and one ear

 

[tommyd87]

In theory you should be able to fully recover. However, that depends on your ear still having functioning support cells.
Without support cells the affected areas can't recover. You'd need to be at least profoundly deaf for that to happen though.
We will see the limits of FX-322 after their phase 2a ends.

I'd say even better because most teens are already damaging their hearing on a daily basis.

They are recoverable. There is no functional difference between the cells in low and high frequency areas. However, low frequencies are deeper in the cochlea and therefore more difficult to reach.
They are already working on a gel to deliver it deeper into the cochlea.

Those are the most affected by FX-322.They are (at least with the current formula) the main frequencies that will recover.

Doesn't matter. People with major hearing loss will obviously benefit the most from it but in the end all that matters is whether you still have supporting cells.

That's our hope and expectation. Otherwise we wouldn't discuss a hearing restoration medication on a tinnitus forum (or maybe not that much).
It's pretty clear that for most people tinnitus is a symptom of hearing loss so it's reasonable to assume that by repairing the underlying damage the symptoms should go too.
But we will have definite answers once Frequency Therapeutics releases their phase 2a data since they are measuring tinnitus as a secondary outcome.

I thought Frequency Therapeutics said they can treat profound hearing loss people as long as they were born with the entire range of hearing to start with. I am pretty sure from research that it is known that they can treat the full spectrum sufficiently providing you could hear at that frequency and also the treatment got to the correct section of the ear.

 

[FGG]

I thought Frequency Therapeutics said they can treat profound hearing loss people as long as they were born with the entire range of hearing to start with. I am pretty sure from research that it is known that they can treat the full spectrum sufficiently providing you could hear at that frequency and also the treatment got to the correct section of the ear.

Frequency has never said that.

The problem is that with profound loss, you lose all of your support cells and FX-322 needs LGR5+ support cells to be the target for their drug.

Other companies are working on this problem but nothing is far along yet.

 

[tommyd87]

Frequency has never said that.

The problem is that with profound loss, you lose all of your support cells and FX-322 needs LGR5+ support cells to be the target for their drug.

Other companies are working on this problem but nothing is far along yet.

Cheers for clarifying. It did not sound accurate at all when I saw that info on another site, suggesting that it would was contrary to the theory of Frequency Therapeutics. I thought the idea was regrowth but only in persons who would have originally had those cells to begin with. Hence why it probably wouldn't work for profound hearing loss.

 

[Jurger]

Frequency has never said that.

The problem is that with profound loss, you lose all of your support cells and FX-322 needs LGR5+ support cells to be the target for their drug.

Other companies are working on this problem but nothing is far along yet.

The research I found is that in people with profound hearing loss, the cochlea has areas with flat epithelium and areas with supporting cells. That's even the case with people who've had a cochlear implant. So I take it FX-322 might still work for the frequencies/areas where supporting cells still exist.

 

[Zugzug]

Does anyone know if this drug would be unsafe for people with, say, autoimmune inner ear disease? I wonder if by some freak accident, this could regrow cells in a way that the immune system no longer thinks is problematic. Seems unlikely.

 

[Jaysterk]

Cheers for clarifying. It did not sound accurate at all when I saw that info on another site, suggesting that it would was contrary to the theory of Frequency Therapeutics. I thought the idea was regrowth but only in persons who would have originally had those cells to begin with. Hence why it probably wouldn't work for profound hearing loss.

Is this an issue with "hearing loss" only?

 

[tommyd87]

Is this an issue with "hearing loss" only?

Give me further information please. I am unsure what you mean.

 

[FGG]

Does anyone know if this drug would be unsafe for people with, say, autoimmune inner ear disease? I wonder if by some freak accident, this could regrow cells in a way that the immune system no longer thinks is problematic. Seems unlikely.

I don't think it can regrow cells in a way to hide from the immune system but I wonder if (and this is just off the cuff speculating) it could be alternated with using OTO-104 (intratympanic sustained released Dexamethasone that lasts a few months) off label.

 

[FGG]

The research I found is that in people with profound hearing loss, the cochlea has areas with flat epithelium and areas with supporting cells. That's even the case with people who've had a cochlear implant. So I take it FX-322 might still work for the frequencies/areas where supporting cells still exist.

Right, it's only in the notches over 90dB that would generally be a problem, not across all frequencies.

 

[WillBeNimble]

Well, hopefully they're able to regenerate the whole high frequency spectrum, from 8kHz to 20kHz, as if we see that, then there's no worries that we'll age past treating high frequency tinnitus. I seriously doubt we'll see that, but I hope. Otherwise, there is a time limit to all this that I worry will pass by or has passed most of us by.

 

[ThomasRobert]

@FGG First of all, Thank you for your inputs and dedication in this community.

Can you please share your view for a case where someone got tinnitus and mild hearing loss (40 dB) from taking ototoxic drugs. Would the damage be to hair cells only, or also damage to support cells? Would FX-322 be the only drug needed for a possible cure? Or do I have to think about synapse issues as well?

Thank you, I wish you and everyone else a speedy recovery...

 

[FGG]

@FGG First of all, Thank you for your inputs and dedication in this community.

Can you please share your view for a case where someone got tinnitus and mild hearing loss (40 dB) from taking ototoxic drugs. Would the damage be to hair cells only, or also damage to support cells? Would FX-322 be the only drug needed for a possible cure? Or do I have to think about synapse issues as well?

Thank you, I wish you and everyone else a speedy recovery...

I personally think you'd be a good candidate.

Based on a conversation I had with one researcher, with widespread support cell loss, hair cells die too and you would see a more profound hearing loss. I don't believe you need 100% of your support cells, just enough of the right ones to be a target for this drug.

As far as synapses, you may also have a separate cochlear synaptopathy (unrelated or in a different area than your hair cell loss) or not. Testing isn't that great in that area yet, unfortunately.

 

[sensualmosquito]

My hearing loss is in the range of 6-8 kHz and comes back at 10 ish kHz, stopping at around 12 kHz. I really want to try this stuff once my right ear has healed more from my acoustic trauma, since it seems to help the most at those high frequencies.