Frequency Therapeutics — Hearing Loss Regeneration

[HootOwl]

So after digging a little deeper into the Frequency Therapeutics paper I think I can conclude with confidence that they did in fact produce IHC as well as OHC in their animal models. I know this has been brought up as a concern before.

Quote 1:
Hair cell colonies were either negative or positive for prestin, a motor protein located in the membrane of outer hair cells, identifying a subset of the differentiated cells as outer hair cells. Colonies of new hair cells also expressed vesicular glutamate transporter3 (vGlut3), an inner hair cell marker, which was only found in colonies that did not express prestin"

Quote 2:
"Our differentiation conditions thus generated inner and outer cochlear hair cell types that contained components of synaptic specializations, the transduction apparatus receptors, and ion channels of hair cells"

Quote 3:
"There was a highly significant (p < 0.001) ∼2-fold increase in myosin VIIa+ inner and outer hair cells after 3 days of drug treatment as compared to control cochlea."

You can see the newly regenerated IHC and OHC here. Myosin VIIa is the bio marker stain used to identify a new hair cell. The arrows are pointing to the existence of supporting cells after trans differentiation.

And finally you also have this graph, which also shows the increase in IHC, followed by this caption.

(B) Increased numbers of inner hair cells, outer hair cells, and total hair cells (IHCs, OHCs, and total HCs) were observed in treated as compared to control cochleae by myosin VIIa (Myo VIIa) expression. n = 4 each. Error bars represent mean ± SD; ∗∗∗p < 0.001.

Unless I'm completely misreading everything here I think if anyone is concerned about IHC regeneration then you should be okay based on the data here (if it translates into humans).

 

[JohnAdams]

I don't see any travel restrictions, like Dr. Shore... I might give this a shot (no pun intended).

Other than the drug itself... are there any complications to worry about with the injections? I'm probably not as spry and resilient as some. ;-)

Yes, if the ENT doing the injection is a numb-nuts then he could tear your eardrum or poke your ossicles, but that is highly unlikely. I bet they have pros doing this. I'm actually really jealous of you if you make it in.

 

[FGG]

I don't see any travel restrictions, like Dr. Shore... I might give this a shot (no pun intended).

Other than the drug itself... are there any complications to worry about with the injections? I'm probably not as spry and resilient as some. ;-)

When I went in, when I asked I was told the only phase 1 reactions were transient dizziness and transient headache. No serious reactions were reported and no one got worse. It was a small sample size but I found that encouraging.

 

[RingingBrother]

Please keep us updated. Do you also experience hyperacusis?

I got noise induced hearing loss and tinnitus since 2018 and recently got some pulsatile tinnitus in my right ear.

Do you think I can get away with talking about it here if I sign an NDA?

 

[Earing]

Dude, there were 4 patients with +100% (yeah, doubled) word recognition scores. That result simply cannot be due to blind chance. Most of the other treated patients had only mild hearing loss and there was little room for improvement, as someone from Frequency reported. (Moreover, researchers explained that most of the drug concentrates in the high-frequency region of the cochlea.)

With regard to tinnitus, I guess it could work where hearing loss is also part of the problem. And I'm curious about OTO-413 (that one should repair damaged synapses) and PIPE-505... my intuition tells me they might have an effect for those of you who have tinnitus but no hearing loss.

When did that change? I thought when the first reports came out they didn't show as much promise as you are referencing. Is there a link to the new (to me) results?

 

[Lucifer]

Do you think I can get away with talking about it here if I sign an NDA?

Just don't mention the days you went in to get the injection.

 

[Heinrich_S7]

You guys realize we are finally talking about regenerating hair cells? We've been waiting so long for this, and it's about to become reality...

It's a great time to be alive.

 

[ChrisBoyMonkey]

You guys realize we are finally talking about regenerating hair cells? We've been waiting so long for this, and it's about to become reality...

It's a great time to be alive.

It will be even greater for people being born after when this is as normal as LASIK.

 

[AfroSnowman]

Do you think I can get away with talking about it here if I sign an NDA?

I second @Lucifer's idea, you could even take it a bit further, purposefully give misdirected personally identifying information i.e: dates, ear it was injected into etc.

 

[Heinrich_S7]

It will be even greater for people being born after when this is as normal as LASIK.

Hopefully its fast track status gets it to market sooner. Crossing my fingers for everyone!

 

[FGG]

Do you think I can get away with talking about it here if I sign an NDA?

Their NDA says no social media. But can you get away with it? Probably. If you leave out anything that can be traced to you.

 

[MrCrybaby]

Do you think I can get away with talking about it here if I sign an NDA?

That's a risky game to play, as much as we'd like to know now, violating an NDA puts you at legal risk (i.e. lawsuit).

Plus only cold hard data brings approval and access, not anecdotes.

 

[hopeful4future]

All this optimism about FX-322 is really making me regret not moving forward with the clinical trial. I really hope this works and gets released someday.

 

[JohnAdams]

Do you think I can get away with talking about it here if I sign an NDA?

Just don't. This is serious.

 

[ThomasC]

How much would FX-322 cost if it was commercialized? My fear is that it would be too expensive for the vast majority of us.

I guess it will depend on how much the research and the development cost and how many people could benefit from the drug.

 

[JohnAdams]

How much would FX-322 cost if it was commercialized?

$322 duh.

It will probably be a little pricey. Supply and demand.

 

[FGG]

$322 duh.

It will probably be a little pricey. Supply and demand.

I imagine the off label/whatever insurance doesn't cover (which will probably be as little as possible) cost will be similar to around what LASIK eye surgery does. Within the reach of many people, especially with payment plans but out of the reach of those living paycheck to paycheck. If I recover and get back to work, I'm going to donate to as many GoFundMes for this treatment as I can, though.

 

[just1morething]

How much would FX-322 cost if it was commercialized? My fear is that it would be too expensive for the vast majority of us.

I guess it will depend on how much the research and the development cost and how many people could benefit from the drug.

I think you're putting the cart before the horse. An unreliable source said $322/ear. That could be a straight cash homey price though.

 

[HootOwl]

I don't see any travel restrictions, like Dr. Shore... I might give this a shot (no pun intended).

Other than the drug itself... are there any complications to worry about with the injections? I'm probably not as spry and resilient as some. ;-)

Good luck! I hope you can get in, and fingers crossed you don't get the placebo.

 

[MRItechssuck]

Hasn't everyone signed up for this? Traveling to Florida seems way better than Ireland... lol

What am I missing? I feel like the kid everyone is telling to go lick the flag pole in winter...

 

[Dosman]

Hasn't everyone signed up for this? Traveling to Florida seems way better than Ireland... lol

What am I missing? I feel like the kid everyone is telling to go lick the flag pole in winter...

If you have no hearing loss in the typically tested range you won't be admitted to the testing group.

 

[HootOwl]

Hasn't everyone signed up for this? Traveling to Florida seems way better than Ireland... lol

What am I missing? I feel like the kid everyone is telling to go lick the flag pole in winter...

Hm, good question. First is probably that an injection already feels more invasive than Lenire, which I completely get as someone who hates needles.

Second is probably how strict the criteria can be. You need a certain amount of loss to get in. In my case I had enough 15-30 dB dips within 13 kHz-16 kHz in both ears to do so but if you're flat across the board or don't hit enough "data points" than it would be a no go :/ you apparently can get away with a normal 8 kHz audiogram tho (like I did), which maybe people aren't aware of.

And still at the end of it all you might get the placebo. Which can be mentally taxing in its own way and I understand why someone might not want to go through that.

 

[FGG]

Hasn't everyone signed up for this? Traveling to Florida seems way better than Ireland... lol

What am I missing? I feel like the kid everyone is telling to go lick the flag pole in winter...

A lot of us tried to get in but they have very specific criteria in this trial. Hearing loss needs to be sudden and there needs to be a consistent audiogram with certain parameters that is stable for at least 6 months prior to participating.

 

[MRItechssuck]

A lot of us tried to get in but they have very specific criteria in this trial. Hearing loss needs to be sudden and there needs to be a consistent audiogram with certain parameters that is stable for at least 6 months prior to participating.

I don't see the hearing loss being sudden... and that many people have had hearing loss changes in 6 months?
I have had two audiograms 20 years apart... oops... lol.

Inclusion Criteria:

1. Established diagnosis of sensorineural hearing loss by standard audiometric measures that is stable for ≥ 6 months prior to the Screening Visit [no changes greater than 5 decibels (dB) in any frequency].
2. Documented medical history consistent with hearing loss being caused by noise exposure or sudden sensorineural hearing loss.
3. Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected

 

[FGG]

I don't see the hearing loss being sudden... and that many people have had hearing loss changes in 6 months?
I have had two audiograms 20 years apart... oops... lol.

Inclusion Criteria:

1. Established diagnosis of sensorineural hearing loss by standard audiometric measures that is stable for ≥ 6 months prior to the Screening Visit [no changes greater than 5 decibels (dB) in any frequency].
2. Documented medical history consistent with hearing loss being caused by noise exposure or sudden sensorineural hearing loss.
3. Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected

From talking to them during my interview, they aren't looking for gradual noise related loss, though, at this time (ie age related or gradual occupational losses). You could call them and ask them to clarify, though, before you travel. If your two audiograms are consistent, i think you'd still qualify.

 

[RB2014]

I think you're putting the cart before the horse. An unreliable source said $322/ear. That could be a straight cash homey price though.

FX-322.....322 dollars. I'm pretty sure that was a joke.

 

[Earing]

$322 per cilia.

 

[JohnAdams]

$322 per cilia.

$322 per life mistake.

 

[HootOwl]

Question: FX is expanding the population of LGR5+ supporting cells before turning them into hair cells correct? I was told by the CSO from Pipeline that LGR5+ cells exist in limited numbers to begin with and to get the amount of OHC regeneration you want you would need to proliferate them first - which is what FX is doing I think.

It's making me wonder about Pipeline and the route of recovery we would want to take with these drugs. Pipeline converts LGR5+ cells without dividing them first, so if you deplete these first would there be nothing for FX to work with?

It almost seems that FX and Pipeline seem to working at odds with each other in some ways (not intentionally of course), which might be a concern for those like myself who suspect they have mild/moderate OHC damage AND synaptopathy - which is also probably the case for a lot of us here.

Perhaps someone more informed than me could clarify. FX doesn't regenerate nerve fibers and synapses in isolation correct? They only saw outgrowth and reconnection of the peripheral axons once the missing IHC/OHC was regenerated? From what I understand FX is not treating synaptopathy at its source, but as a secondary result stemming from the newly regenerated hair cell.

 

[mrbrightside614]

Hm, good question. First is probably that an injection already feels more invasive than Lenire, which I completely get as someone who hates needles.

Second is probably how strict the criteria can be. You need a certain amount of loss to get in. In my case I had enough 15-30 dB dips within 13 kHz-16 kHz in both ears to do so but if you're flat across the board or don't hit enough "data points" than it would be a no go :/ you apparently can get away with a normal 8 kHz audiogram tho (like I did), which maybe people aren't aware of.

And still at the end of it all you might get the placebo. Which can be mentally taxing in its own way and I understand why someone might not want to go through that.

Where'd you get your high frequency audiogram? Did they conduct it themselves? I'm also guessing that you've been admitted into the trials?

Question: FX is expanding the population of LGR5+ supporting cells before turning them into hair cells correct? I was told by the CSO from Pipeline that LGR5+ cells exist in limited numbers to begin with and to get the amount of OHC regeneration you want you would need to proliferate them first - which is what FX is doing I think

You are correct. The supporting cell is reported to split into another supporting cell in addition to an active progenitor cell.