Frequency Therapeutics — Hearing Loss Regeneration

[Philip83]

Hey, do you think that once Phase 2a clinical trials are completed, Frequency Therapeutics will do clinical trials in other locations (outside of the US)?

If I remember correctly, there is a paragraph in the agreement of the partnership between Frequency Therapeutics and Astellas that states that there will be a monetary payout from Astellas when the first patient is injected in Europe in a Phase 2 study.

So I'm pretty sure it's in the plans, but I guess it depends on how everything goes in the currently running phases.

 

[FGG]

If I meet all the other criteria, would this audiogram qualify me for a Phase 2/3 trial?

If the criteria stays the same as they are now.

All I can find is that one should have hearing loss between 25-70 dB.

View attachment 42141

They finished recruiting for Phase 2a already and are now recruiting for severe hearing loss, which you don't appear to qualify for.

They haven't released the pivotal phase's criteria yet (and won't until recruitment) but my guess is you'd likely qualify.

 

[FGG]

Hey, do you think that once Phase 2a clinical trials are completed, Frequency Therapeutics will do clinical trials in other locations (outside of the US)?

Seems to be the case based on the Astellas partnership.

 

[Philip83]

They finished recruiting for Phase 2a already and are now recruiting for severe hearing loss, which you don't appear to qualify for.

They haven't released the pivotal phase's criteria yet (and won't until recruitment) but my guess is you'd likely qualify.

Yes, I didn't mean the current trials, but if the criteria would be the same for a potential trial in Europe.

 

[Diesel]

If I meet all the other criteria, would this audiogram qualify me for a Phase 2/3 trial?

If the criteria stays the same as they are now.

All I can find is that one should have hearing loss between 25-70 dB.

View attachment 42141

Your audiogram would meet the acceptance criteria for Phase 2A; so if similar criteria carries to a Phase 2B/3, then you would likely be accepted.

 

[sami23]

Okay thanks a lot.

I have one final question. My acoustic otoemission (OAE) has decreased with noise trauma, is this sufficient to prove that there is hair cells loss?

I don't have hearing loss but tinnitus and daily sounds are very unpleasant when I hear them (like sirens, motorbikes etc...). When my ears were fine I didn't pay any attention to these noises.

 

[Gb3]

If I meet all the other criteria, would this audiogram qualify me for a Phase 2/3 trial?

If the criteria stays the same as they are now.

All I can find is that one should have hearing loss between 25-70 dB.

View attachment 42141

Have you tried hearing aids? They might help due to your hearing loss not being that bad.

 

[Philip83]

Have you tried hearing aids? They might help due to your hearing loss not being that bad.

I did try the Lyric hearing aids, which aren't actual hearing aids I've learned, but rather just "amplifiers". They made my noxacusis/hyperacusis go through the roof though, so I had to stop using them. And when my hyperacusis now is even worse since my latest "trauma", I'm a bit reluctant to try any again, but I might give it a shot.

The Lyrics did lower the perception of my tinnitus quite substantially though, so it's a bummer my hyperacusis got worse...

 

[FGG]

Okay thanks a lot.

I have one final question. My acoustic otoemission (OAE) has decreased with noise trauma, is this sufficient to prove that there is hair cells loss?

I don't have hearing loss but tinnitus and daily sounds are very unpleasant when I hear them (like sirens, motorbikes etc...). When my ears were fine I didn't pay any attention to these noises.

I'm confused. Someone said you had abnormal otoacoustic emissions but no hearing loss? That test is one measure of OHC related hearing loss.

Or do you mean that you personally don't notice your hearing loss?

Frequency Therapeutics is looking for specific audiogram changes for the purposes of the trial if that's what you were also asking.

 

[Gb3]

I did try the Lyric hearing aids, which aren't actual hearing aids I've learned, but rather just "amplifiers". They made my noxacusis/hyperacusis go through the roof though, so I had to stop using them. And when my hyperacusis now is even worse since my latest "trauma", I'm a bit reluctant to try any again, but I might give it a shot.

The Lyrics did lower the perception of my tinnitus quite substantially though, so it's a bummer my hyperacusis got worse...

Well all hearing aids are really just amplifiers.

Why did you try such an expensive hearing aid?

Your range could be treated with a basic Phonak hearing aid.

 

[tommyd87]

I think the main issue is that they mainly deal with hearing aids, and that they only work up to 8000 hz Hz far as I know. The audiologists working "on the floor" probably have a narrow view of things.

It certainly would make the need for audiologists lesser, but FX-322 wouldn't solve the need for CI implants, conductive hearing loss and more. Are there surgeries coming up for that?

I think that FX-322 would solve a lot of need for CIs in those that need them through the fact that hearing aids are actually ineffective for them. This is why there was probably some critical commentary on FX-322 from the guy who works with the hybrid CIs because any similar medicine as FX-322 is going to reduce the need or demand for these.

 

[tommyd87]

Well all hearing aids are really just amplifiers.

Why did you try such an expensive hearing aid?

Your range could be treated with a basic Phonak hearing aid.

I don't necessarily agree with this. There are two things that some hearing aids are able to deal with which others cannot (the Lyric being one of those). Hearing aids can amplify only the sounds you need to hear and also assist with reducing the background noise. This tends to vary also on the level of hearing aids you get. Going off of this there are times that the cheaper/basic devices won't work with what you need because despite having a mild loss, you could have really poor understanding in noise for example.

 

[Diesel]

Random thought of the day...

Frequency Therapeutics claims that FX-322 will work on IHCs/OHCs that are "missing" or "damaged" but not "functionally normally".

1. Assuming there is some level of "wear" between a normally functioning cell and damaged cell, what do we suppose is the level of 'wear' that makes a cell considered damaged from a biological standpoint?

2. In cases of cochlear synaptopathy. If I understand correctly, it is possible for a "normal" hair cells to absorb some level of insult and become disconnected at the synapse. Doesn't it seem likely that whatever insult caused enough damaged to disconnect the synapses, would also cause enough wear where the organ would see the cell as damaged and FX-322 to work?

 

[FGG]

Random thought of the day...

Frequency Therapeutics claims that FX-322 will work on IHCs/OHCs that are "missing" or "damaged" but not "functionally normally".

1. Assuming there is some level of "wear" between a normally functioning cell and damaged cell, what do we suppose is the level of 'wear' that makes a cell considered damaged from a biological standpoint?

2. In cases of cochlear synaptopathy. If I understand correctly, it is possible for a "normal" hair cells to absorb some level of insult and become disconnected at the synapse. Doesn't it seem likely that whatever insult caused enough damaged to disconnect the synapses, would also cause enough wear where the organ would see the cell as damaged and FX-322 to work?

Reportedly, the synapses are just that much more sensitive (to noise anyway). You can apparently have synaptopathy with a completely normal IHC based on histology anyway.

 

[Philip83]

Well all hearing aids are really just amplifiers.

Not according to the audiologist I saw the other day. He seemed pretty knowledgeable about a range of hearing aid companies, and he said Lyric are not as good as some other brands, and he wouldn't give them the status of a "normal" hearing aid. Then again, his words, not mine.

Why did you try such an expensive hearing aid?

I actually joined a trial to assess if they could improve tinnitus, so it was for free

 

[FGG]

Not according to the audiologist I saw the other day. He seemed pretty knowledgeable about a range of hearing aid companies, and he said Lyric are not as good as some other brands, and he wouldn't give them the status of a "normal" hearing aid. Then again, his words, not mine.

I actually joined a trial to assess if they could improve tinnitus, so it was for free

They likely were pointing to the digital filtering functions of modern hearing aids. They can amplify and filter (and even alter frequencies so you hear them differently).

 

[Gb3]

Not according to the audiologist I saw the other day. He seemed pretty knowledgeable about a range of hearing aid companies, and he said Lyric are not as good as some other brands, and he wouldn't give them the status of a "normal" hearing aid. Then again, his words, not mine.

I actually joined a trial to assess if they could improve tinnitus, so it was for free

Lyric is made by Phonak. It's basically their top of the line unless this is some brand I don't know about.

 

[d'Wooluf]

Not according to the audiologist I saw the other day. He seemed pretty knowledgeable about a range of hearing aid companies, and he said Lyric are not as good as some other brands, and he wouldn't give them the status of a "normal" hearing aid. Then again, his words, not mine.

I've heard audiologists on HearingTracker say that the Lyric's main use has always been to get people through the door. Once the client realises its limitations he/she is steered in the direction of a 'real' hearing aid.

Lyric is made by Phonak. It's basically their top of the line unless this is some brand I don't know about.

I wouldn't say that. Being analog, it's off on a branch by itself. I've never heard anyone say it works better than a premium digital hearing aid.

 

[Diesel]

Reportedly, the synapses are just that much more sensitive (to noise anyway). You can apparently have synaptopathy with a completely normal IHC based on histology anyway.

Ok, to follow up on this..

It's possible though that an IHC with disconnected synapses would still continue to absorb wear over time (stereocilia, etc), even though it isn't sending signals to the nerve?

 

[FGG]

Ok, to follow up on this..

It's possible though that an IHC with disconnected synapses would still continue to absorb wear over time (stereocilia, etc), even though it isn't sending signals to the nerve?

Sure.

I imagine with severe synaptopathy, there is very likely at least some hair cell damage with it but not necessarily with mild synaptopathy.

 

[sssing]

I sometimes feel like my tinnitus comes from my brain, and not just my ears.

Would FX-322 help with that?

I don't mean to be misleading but it's 100 percent correct. Tinnitus is generated by the brain, not the ears. The electrical signal sent by the ears through the nerve to the brain is interpreted as sound. With tinnitus, some population of neurons responsible for hearing synchronises and are hyperactive even in the presence of no sound. This adulterated signal causes the neurons of your touch and movement to become hyperactive too and that's why after I got tinnitus I realised that bending and turning my neck had a sound.

So how might FX 322 work since this thing is generated in the brain? Most of us here think that by restoring the ears' ability to send electrical signals properly through the ears would therefore lead to these subpopulation of hyperactive neurons to return to normal as they receive a better and accurate signal from the ears.

 

[sami23]

How do we know if we have dormant hair cells in our cochlea?

 

[ThomasRobert]

How do we know if we have dormant hair cells in our cochlea?

Go here on page 239, read post No. 7164 and 7165

Or click here:
https://www.tinnitustalk.com/posts/510177/

 

[patorjk]

Looks like Christopher Loose (co-founder) is no longer selling shares. In April he started selling a handful every 2 weeks. His last sale occurred on 11/5/2020. It really looks like he tried to time things, since his sales post-September 30th were his biggest. He has 71k shares left (he started with a little over 200k).

David Lucchino (CEO) is still selling shares every month, but he has a ton left (323k).

 

[Lucifer]

Looks like Christopher Loose (co-founder) is no longer selling shares. In April he started selling a handful every 2 weeks. His last sale occurred on 11/5/2020. It really looks like he tried to time things, since his sales post-September 30th were his biggest. He has 71k shares left (he started with a little over 200k).

David Lucchino (CEO) is still selling shares every month, but he has a ton left (323k).

Thanks for this patorjk.

Do you have a website link where I can view how many shares do the CEO and Co-Founder have and how many shares they have sold?

I wonder what could be the reason why Christopher Loose is not selling his shares every 2 weeks. Maybe the results have been looking positive and knows he will make a lot of money when FX-322 comes out in the market and wants to maximise his rate of return on his investment.

 

[sami23]

How many hair cells can FX-322 regrow with a single shot?

Will our ears become as good as they were before we got our hearing loss / tinnitus?

 

[Lucifer]

How many hair cells can FX-322 regrow with a single shot?

Will our ears become as good as they were before we got our hearing loss / tinnitus?

It's hard to say. What they found is that those who got one dose of FX-322 were able to maintain their improved hearing from the drug for more than 21 months when they retested their hearing again.

Imagine what if those patients were to get a maximum of 4 doses of FX-322. They would improve their hearing by a lot but also get rid of their tinnitus as well.

 

[100Hz]

I imagine with severe synaptopathy, there is very likely at least some hair cell damage with it but not necessarily with mild synaptopathy.

I've been thinking about this from the OHC perspective where the ribbon synapses increase in number upon noise trauma, and how FX-322 could be useful for this.

The extra ribbons are part of the the actual OHC, I understand. That would suggest that OHCs have to still be intact for this route of type II sensitization to even happen. If the OHCs are damaged however to a point where FX-322 would recognize them as needing regeneration would that mean that the damaged OHC along with its extra type II ribbons be disposed off before the regeneration? If the OHC was still very much intact however then I guess it would be left alone along with its extra ribbons.

I am starting to wonder if this route of sensitization might make more sense for people with noxacusis as there has to still be a hair cell there, and if there is still a hair cell there responding to noise then it would sending extra pain signals on the extra ribbons? It could also explain a lot cases of noxacusis with still generally good audiograms otherwise.

 

[FGG]

I've been thinking about this from the OHC perspective where the ribbon synapses increase in number upon noise trauma, and how FX-322 could be useful for this.

The extra ribbons are part of the the actual OHC, I understand. That would suggest that OHCs have to still be intact for this route of type II sensitization to even happen. If the OHCs are damaged however to a point where FX-322 would recognize them as needing regeneration would that mean that the damaged OHC along with its extra type II ribbons be disposed off before the regeneration? If the OHC was still very much intact however then I guess it would be left alone along with its extra ribbons.

I am starting to wonder if this route of sensitization might make more sense for people with noxacusis as there has to still be a hair cell there, and if there is still a hair cell there responding to noise then it would sending extra pain signals on the extra ribbons? It could also explain a lot cases of noxacusis with still generally good audiograms otherwise.

The "extra synapses" connecting to the OHCs in rodents (we still don't know of this applies to people) in noxacusis sufferers specifically are not the same synapses.

The ribbon synapses in "cochlear synaptopathy" are between the inner hair cells and the spiral ganglion nerve.

But to your question, there is still an intact outer hair cell with type 2 pain fiber sensitization. There would have to be or there would be nothing to synapse to.

It's possible that neighboring damaged hair cells are leaking ATP and have stimulated the intact hair cells, though. It's also possible that damaged cells leak ATP and then recover and the fibers are still sensitized but if the cells underwent apoptosis instead, then yes there would be no OHC there for the pain fibers in noxacusis to synapses to (and respond to sound with pain from).

 

[100Hz]

It's possible that neighboring damaged hair cells are leaking ATP and have stimulated the intact hair cells, though. It's also possible that damaged cells leak ATP and then recover and the fibers are still sensitized but if the cells underwent apoptosis instead, then yes there would be no OHC there for the pain fibers in noxacusis to synapses to (and respond to sound with pain from).

Yeh it seems pretty obvious now doesn't it that there has to be an OHC there for the extra ribbons synapses to even happen (for type IIs). With the ATP / dead hair cell route though, only based on a few diagrams I've found and I'm trying to find more to help back it up, it appears that type II afferents connect (I wouldn't say synapse exactly), to support cells as well as actual hair cells, I wonder if this is the case then could type IIs be susceptible to ATP via support cells as well, or does it takes a functioning OHC to actually begin transmission of the signal. Your other theories above are also very interesting.

Here's one of the diagrams showing the type II connecting to a support cell:

In other words if all hair cells were dead, yet all type IIs sensitized, would there even be a mechanism / pathway for a pain signal anymore.