Frequency Therapeutics — Hearing Loss Regeneration

Nightmare isn't it.

 

Stay safe! South Korea has likely seen the worst of COVID-19 in their country because their private sector was permitted to develop tests months ago.

In the United States, our FDA has tighter regulations and the private sector is only just now allowed to take action.

I understand that things can get worse. I'm only saying that as of now, the death toll here is pretty low and there's no reason to prematurely fear the death of top researchers!

 

That does make sense.

I have no clue, but I'm going to pretend it's likely that synapse damage without corresponding hair cell damage will be minimal.

I've also been taking Lion's Mane (Hericium erinaceus) mushroom capsules daily for a while, which according to science can help repair nerve damage for the duration that you take it. So fingers crossed that will help any synapse issues.

 

They have said in their JP Morgan Q and A that the synapses are repaired *only* in places where hair cells are regenerated. Ie: if you have cochlear synaptopathy without hair cell loss in a location, the drug won't work.

 

I always had it mild since I was 10 but made it a lot worse with hearing damage after a loud concert.

 

Thanks that makes perfect sense!

I wonder how common cochlear synaptopathy without hair cell loss is? Especially with noise-induced hearing loss?

 

I don't think anyone knows for sure but I believe synapses are generally more prone to being damaged and can be damaged with more mild insults.

 

I'm pretty sure this has been the focus of much of Charles Liberman's work on hidden hearing loss - that the nerve connections are far more vulnerable to damage and that this type of damage can be widespread even with a normal audiogram. Don't have the specific journal articles on hand but there's an interview with him here where he talks more about it.

https://www.entandaudiologynews.com...-conversation-with-professor-charles-liberman

But idk I guess it's difficult to know for sure given it's impossible to go in and image a living person's ear.

 

How do you cope with it? And do you think FX-322 will work for us noise induced hearing lost and tinnitus folks?

 

Still trying to figure out how to cope with it and all the shame and regret for causing it. It's a daily struggle.

I do think FX-322 will help, but those of us with low frequency damage will have to wait for another formulation that can penetrate below 3500 Hz. We will also need an effective synaptopathy drug to touch up remaining hair cells with damaged synapses.

 

This is correct, I've read it too.

Decibel Therapeutics' approach may be better for those with tinnitus and normal audiograms (like myself).

 

Thank you for responding. Try using white noise. And how long do you think it will take until they come up with another formulation for us?

 

So were they.

 

From the article: "As soon as we got the new staining techniques working, we saw that noise exposures caused dramatic loss of synapses on surviving inner hair cells, even in ears where thresholds had completely recovered."

Yeah, this doesn't sound like good news for FX-322. He also goes on to say it's likely that disconnected synapses could be a cause for tinnitus... damn. I guess I have to find another drug to watch alongside FX-322?

 

We don't know, but that was one of my questions for the podcast. Frequency needs to reformulate first, which could theoretically begin soon considering @FGG pointed out they had a job posting for some kind of formulation specialist on their website. Then there's the question of whether or not the reformulation would require a whole new batch of clinical trials.

 

Decibel dropped their cochlear neuropathy drug. I believe their focus is now only on preventing Cisplatin toxicity, congenital deafness, and a hair cell regenerative compound that is still in preclinicals.

 

Decibel isn't developing a synaptopathy drug anymore. They have switched gears to develop other parts of their pipeline (including genetic hearing loss and balance orders). They haven't completely abandoned acquired hearing loss, though, as they just bought the rights to the LATS inhibitors being researched at The Rockefeller University.

Otonomy has a synaptopathy drug in phase 2 and Pipeline has one about to start phase 1, though.

 

The new hair cell makes the necessary synaptic connections, otherwise they’d be non-functional. If you have synaptic damage with no hair cell loss in the area, it won’t fix that.

However, I don’t think many people's problems are primarily derived from auditory nerve damage. I’m only guessing, but I think hair cell damage is much more common and a more typical source of tinnitus.

 

Yeah it's a bit confusing but didn't Frequency say in one of their presentations that like 90% of hearing loss is due to hair cell loss?

 

How come Decibel dropped their synaptopathy drug?

 

OTO-413 and PIPE-515. They've each got their own thread in the Research News section.

 

Hopefully they don’t do clinical trials but at the same time I understand the reason for people's safety but seriously it’s hard to wait.

 

Ya this is kinda irking me, too. I hope it signals that they have complete confidence in the other players to fulfill the need.

 

But at least they didn't drop anything while in clinical trials. That would have been much worse news imo. It seems like just a reprioritizing.

 

I hope you're right! I certainly hope that FX-322 will fix my noise-induced issues. I unquestionably have hair cell loss (I've had countless acoustic traumas) and expect Frequency's drug to help there.

What has me concerned is Charles Liberman's take on it, but I might be misunderstanding things...

He used the word "dramatic" when describing the level of synapse loss concerning still intact hair cells in ears that suffered acoustic trauma... but maybe you've already considered this?

I am working from a very limited understanding here!

 

Imagine if Frequency Therapeutics were to drop FX-322 and focus on something else. Likelihood of that happening is 0.01% since they got a lot of funding from Astellas which to me suggests FX-322 helps with hearing loss but whether it helps with tinnitus and hyperacusis we are not too sure on.

Good thing the podcast with Frequency Therapeutics is happening next month. I was not expecting to hear from them anytime soon so I would like to say thank you to the guys that got this interview to happen. When I first saw that the interview was happening I had an OMG reaction lol.

 

This is what the synaptopathy drugs will be for. If you've had multiple acoustic traumas (concerts etc.) then chances are you have widespread synaptic damage, too. FX-322 is one piece to the puzzle, it's a big one, but it may not be everything you need.

 

Here we go again.. getting back on the synaptopathy or hair cell damage research/article swap carousel again!

I for one am looking forward to what Carl LeBel from Frequency Therapeutics will be discussing on the upcoming Tinnitus Talk Podcast. Perhaps that will put a lot of these revolving discussions to bed.

@FGG, @mrbrightside614, would you be interested or able to provide this discussion with any updates/reminders on a regular basis to keep the upcoming Tinnitus Talk Podcast at "top of mind?" It's already buried a few pages back.

 

Imo, there is a 0% chance that they would drop a drug in phase 2 just to "work on something else." The only way they would drop it is if something negative and completely unforeseen happens in phase 2 with safety or results. The phase 1 results make that seem really unlikely to me.

Decibel's synapse drug never even filed an IND. Big difference.

 

I'm currently working with @Candy on making a "laymen's guide to regenerative drugs in clinical trial". Or I should say I have just started! The goal will be something simplified and accessible stickied at the top with the basic info about each drug that could of course be edited as new info comes out.