Frequency Therapeutics — Hearing Loss Regeneration

[Jorge1984]

Hello everyone, I'm curious where are the little hairs located in our ear?

 

[Juan]

There was only ever one NY location (Amherst).

Did you try this therapy?

 

[Juan]

The permanent hearing loss (and hearing decline) is related to the hair cell death, though. I wonder if FX-322 in conjunction with a salt restricted diet and diuretics would help once the drug can reach the lower registers.

I'm not too sure about that. Maybe it is synapses that disappear or change, or hair cells are just bent but still alive, or there is damage to the hearing nerve or its coating.

 

[FGG]

Did you try this therapy?

I tried to get in the trial but was rejected unfortunately. Not at the NY location, though.

 

[FGG]

I'm not very informed on the subject but it seems that without the IHC's no signal would go through, even when OHC's are still present.

That's exactly what I would think but somehow you can lose close to 100% of IHCs in a spot and still hear pure tones. Don't ask me how. It makes zero sense to me but that appears to be the case.

 

[FGG]

I'm not too sure about that. Maybe it is synapses that disappear or change, or hair cells are just bent but still alive, or there is damage to the hearing nerve or its coating.

Meniere's does not affect the auditory nerve. I have never heard it affects the synapses but I guess it's possible.

 

[FGG]

Hello everyone, I'm curious where are the little hairs located in our ear?

In the cochlea. You have 3 rows of outer hair cells (OHCs) and 1 row of inner hair cells (IHCs).

 

[Bartoli]

That's exactly what I would think but somehow you can lose close to 100% of IHCs in a spot and still hear pure tones. Don't ask me how. It makes zero sense to me but that appears to be the case.

Wouldn't that be the off-frequency listening they refer to in the study I posted?

 

[Jorge1984]

In the cochlea. You have 3 rows of outer hair cells (OHCs) and 1 row of inner hair cells (IHCs).

Thank you.

 

[Juan]

That's exactly what I would think but somehow you can lose close to 100% of IHCs in a spot and still hear pure tones. Don't ask me how. It makes zero sense to me but that appears to be the case.

When one loses ability to understand speech in noise, it is still easy to enjoy music. That's a big difference!

 

[GregCA]

This is the "fluctuating hearing loss" but over time, I believe there is permanent hearing loss from ischemia killing off hair cells (versus the effects of hydrops where hearing and tinnitus can get much better after an "attack").

I did not know that this was a common outcome. I thought that Meniere's Disease was essentially a permanent establishment of the unusual pressure condition. The reason I believed that is that a few treatments that are proposed for Meniere's Disease would not make sense if the hair cells were already dead, for example:

• gentamycin injections: they are meant to actually kill the hair cells, so they cannot sending "bogus signals" anymore, which wouldn't be needed if they were already dead
• endolymphatic sac decompression surgery: meant to actuate on the pressure and restore a normal state on hair cells, which would be unneeded if the hair cells were already dead

Perhaps these are only offered when the patients haven't progressed to a severe stage?

 

[FGG]

I did not know that this was a common outcome. I thought that Meniere's Disease was essentially a permanent establishment of the unusual pressure condition. The reason I believed that is that a few treatments that are proposed for Meniere's Disease would not make sense if the hair cells were already dead, for example:

• gentamycin injections: they are meant to actually kill the hair cells, so they cannot sending "bogus signals" anymore, which wouldn't be needed if they were already dead
• endolymphatic sac decompression surgery: meant to actuate on the pressure and restore a normal state on hair cells, which would be unneeded if the hair cells were already dead

Perhaps these are only offered when the patients haven't progressed to a severe stage?

Gentamycin is used in Meniere's to kill the vestibular hair cells, not the OHCs/IHCs. It is primarily vestibulotoxic and that's why it is used.

Decompression surgery also is not used to improve hearing outcomes, just reduce vestibular symptoms.

 

[Jack V]

I tried to get in the trial but was rejected unfortunately. Not at the NY location, though.

Can you try to get in again, adjusting certain responses (such as your availability, for example, if you're willing to relocate to their area for a month)?

 

[Lucifer]

There was only ever one NY location (Amherst).

I'm pretty sure there were 2 New York locations. I checked the locations again and Florida seem to have 3 locations now. Before it was only 2.

They still have estimated participants at 96.

 

[FGG]

I'm pretty sure there were 2 New York locations. I checked the locations again and Florida seem to have 3 locations now. Before it was only 2.

They still have estimated participants at 96.

I distinctly remember 3 Florida locations:

2 around the Tampa Bay Area and 1 South Florida location.

I also don't recall more than 1 NY location.

 

[FGG]

Can you try to get in again, adjusting certain responses (such as your availability, for example, if you're willing to relocate to their area for a month)?

I was ultimately rejected for my audiogram so it wouldn't do any good.

 

[serendipity1996]

Nothing constructive to add, just want to say a big thank you to all those on here who spend time finding papers, updates, and tirelessly and patiently explaining concepts so that we can better understand this condition and the research that is being done to help us. It's really uplifting on bad days.

 

[Lucifer]

Nothing constructive to add, just want to say a big thank you to all those on here who spend time finding papers, updates, and tirelessly and patiently explaining concepts so that we can better understand this condition and the research that is being done to help us. It's really uplifting on bad days.

I've been checking for updates everyday so I can let you guys know and post it on here.

 

[GregCA]

Gentamycin is used in Meniere's to kill the vestibular hair cells, not the OHCs/IHCs. It is primarily vestibulotoxic and that's why it is used.

I thought it killed indiscriminately? (we'd want it to target vestibular regions, but we don't get to choose where the meds diffuse, so we end up with "collateral damage" in the cochlea because it is also toxic to the hair cells in the cochlea)

Decompression surgery also is not used to improve hearing outcomes, just reduce vestibular symptoms.

Does it not improve hearing outcomes?

 

[FGG]

I thought it killed indiscriminately? (we'd want it to target vestibular regions, but we don't get to choose where the meds diffuse, so we end up with "collateral damage" in the cochlea because it is also toxic to the hair cells in the cochlea)

Does it not improve hearing outcomes?

They are not indiscriminate at all. Below is a link to a slide I found online but there is a ton of literature about this. There is a reason gentamycin in particular is used.

https://slideplayer.com/slide/43375...totoxicity+first+with+Streptomycin+(1944).jpg

Decompression surgery does not improve hearing. It reduces or halts vestibular attacks and slows the progression of the hearing loss associated with repeated Meniere's attacks.

 

[GregCA]

They are not indiscriminate at all. Below is a link to a slide I found online but there is a ton of literature about this. There is a reason gentamycin in particular is used.

I agree, but isn't it the case that, even though gentamicin targets vestibular cells, it is also toxic to cochlea cells? I thought that was the reason explaining the hearing loss side effect from gentamicin treatment?

This page has interesting explanations about loss of hearing due to the treatment, with various dosage:
https://www.dizziness-and-balance.com/treatment/ttg.html

 

[FGG]

I agree, but isn't it the case that, even though gentamicin targets vestibular cells, it is also toxic to cochlea cells? I thought that was the reason explaining the hearing loss side effect from gentamicin treatment?

This page has interesting explanations about loss of hearing due to the treatment, with various dosage:
https://www.dizziness-and-balance.com/treatment/ttg.html

What I have always understood is it is not well taken up by cochlear cells but with very high doses I'm sure it's toxic to everything it touches.

It is very highly selective for vestibular cells. You can obliterate the vestibular system (the point of the treatment in Meniere's obviously) and not get audiogram or noticeable hearing changes.

In any case, I think the hair cell loss in Meniere's will be just as amenable to treatment but the drug may work better when hydrops is better controlled.

 

[pinklights98]

I'm trying to be optimistic about this treatment but isn't it true that it won't impact frequencies below 3000 Hz? What about those of us who have tinnitus below this frequency?

 

[FGG]

I'm trying to be optimistic about this treatment but isn't it true that it won't impact frequencies below 3000 Hz? What about those of us who have tinnitus below this frequency?

The full dosing won't reach that range per their presentations. I think it's quite plausible they will reformulated in some way to reach the lower frequencies but that may happen a year later. They had job postings recently to hire someone with formulation experience including, intratympanic drug formulations. FX-322 is the only drug in the platform that is for intratympanic use. I think it's a really good sign they hope to eventually get all frequencies.

 

[Pink Noise]

If FX-322 can help reduce or eliminate this monster >12 kHz sickening ring in my head I will be pleased. I have other lower tones (sub 3 kHz) going on but those are no way near as unsettling as the the high pitch screech. When I work in the studio I have to put a low pass filter on the music just to prevent high frequency overload. It's really upsetting.

Come on Frequency I'm ready to give you some cash.

 

[Danneskjöld]

Come on Frequency I'm ready to give you some cash.

In a way you already can. Go buy some stock.

 

[Tweedleman]

The full dosing won't reach that range per their presentations. I think it's quite plausible they will reformulated in some way to reach the lower frequencies but that may happen a year later. They had job postings recently to hire someone with formulation experience including, intratympanic drug formulations. FX-322 is the only drug in the platform that is for intratympanic use. I think it's a really good sign they hope to eventually get all frequencies.

And isn't Audion's Regain ironically supposed to have better penetrance at the apex? So worst case scenario perhaps we could combine the two treatments? Although I would rather have Frequency be able to cover everything in the interest of preserving support cells.

 

[FGG]

And isn't Audion's Regain ironically supposed to have better penetrance at the apex? So worst case scenario perhaps we could combine the two treatments? Although I would rather have Frequency be able to cover everything in the interest of preserving support cells.

They haven't said nearly as much about their product as Frequency has.

 

[Lucifer]

And isn't Audion's Regain ironically supposed to have better penetrance at the apex? So worst case scenario perhaps we could combine the two treatments? Although I would rather have Frequency be able to cover everything in the interest of preserving support cells.

Audion/Regain will release their results in May so they may mention more about the drug but Frequency Therapeutics have been more open about FX-322.

 

[Pero1234]

Audion/Regain will release their results in May so they may mention more about the drug but Frequency Therapeutics have been more open about FX-322.

We can't buy stock from Audion, can we?

Anyone else keeping an eye on the Frequency Therapeutics stock? It's not too high at the moment.