Frequency Therapeutics — Hearing Loss Regeneration

So, if FX-322 shows similar successful results as it did in the recent single dose study, is it likely to go to market?

 

Cochlear hydrops only affects the auditory system and not the semi-circular canals for balancing, correct? Maybe after FX-322 hits (and FX-345 after that), Frequency Therapeutics would come out with a FX-368 (? - I don't know their naming nomenclature) for full cochlear coverage. To be honest, I have more lower frequency hearing loss than higher based on my audiogram, and do have dizzy spells so I'm probably early onset Menière's.

A hypothetical is using the location of the ultra frequency hearing cells (16 kHz to 20 kHz) for lower frequency hearing by adjusting the length of the stereocilia - 10 to 50 micrometers (μm), maybe like a wind chime or xylophone that produces different pitches based on the length of the bars. I think a lot of the reasoning for FX-322 is also based on the brain's ability to receive and process ultra frequencies which through natural aging and neuroplasticity has "forgotten" how to. It can't comprehend why it would be receiving this input which goes against evolution. I think some FX-322 trial enrollees have better brains to handle this newfound input whereas others, the brain's thinking "What in the... is this ish?"

Sadly we're likely a long time off from doing specialized treatments like this, focus now is just being able to regenerate hair cells with PCA and orphaned ribbon synapse reconnections with BDNF/NT-3.

@Jelonek - I do love these speculative ideas, keeps my mind of my tinnitus.

 

Yes.

 

I would only trade FREQ on news, not on a single word written on this thread. Volume trading is linked to this thread. A few front load shares - post and then later dump. Pump and dump.

 

I've been reading a lot about hidden hearing loss / cochlear synaptopathy over the last few days. This has led me to wonder about if/how the Frequency Therapeutics drugs are supposed to be able to treat nerve degeneration in the inner ear. If FX-322 is able to regenerate hair cells, but not the correct nerve connections to the brain from the ear and vice versa, how can it improve hearing?

 

Sounds like a question for @Chad Lawton.

 

I'm almost convinced that the synaptic ribbons within the inner ear will be easier to regenerate. Regenerative medicine like PRP and stem cells are already used to regenerate nerves even years after the damage on other nerves, and studies show that the synaptic ribbons do partially regenerate on their own for a short time, so some limited form of regeneration already exists somehow. I often wonder why the regeneration can happen partially after injury, but cannot continue. Insufficient supply of healing properties? Scarring?

Can we really overcome this difference from intratympanic injections? I think it's possible, but there probably needs to either be some form of compound that can encourage a significant amount of regeneration within a short amount of time, or one that works, but has to be used a lot to reverse the damage.

Also, I could have sworn I saw a study where someone restored the hair cells through a gene therapy, and managed to fix the synapse by accident, but I cannot find it. Hope I wasn't imagining things.

 

If you regenerate the hair cell, the synapse restores on its own.

Stanford's Initiative to Cure Hearing Loss

Around the 29:00 mark.

 

Amazing. Thank you for this. But what about the (still present) damaged hair cells? Would they need to be destroyed before they could be replaced by functional ones?

 

This was exactly what I was thinking about. Thank you!

Probably. Makes me wonder what would be considered "gone" to the body before they get replaced. However, the question remains on whether or not damaged hair cells that are still (barely) functioning can be repaired. I'm hoping they can be, through some form of intervention.

 

Otonomoy's OTO-6XX is aimed at hair cell "repair" instead of regeneration. Unfortunately the company is in a really bad shape so I don't know if the drug will ever get released.

 

That's unfortunate. Well, if Frequency Therapeutics is as successful as they seem to be heading, maybe they could buy off the research, if they deem its existence valid.

 

Not likely. Their research is positioned to activate progenitor cells throughout the body. After focusing on the ear with FX-322 / FX-345, they're working on applying the same for cells relating to MS.

 

From what I understood reading the OTO-X13 threads, one of Otonomy's main assets is the delivery method they developed for their drugs. Maybe that could be of interest to Frequency Therapeutics?

 

How can we know whether FX-322 would be suitable for our hearing issues? I have no hearing loss on an audiogram but I can definitely say that I hear worse after the trauma. Is there a way to check who would gain something positive out of the drug? Is audiogram the only indicator?

 

Do you know that an audiogram measures pitches only at discrete frequencies? The tiny strips of frequencies that you've lost, which contribute to your tinnitus, are so scarcely distributed in your hearing range that you'd need a far more accurate test to detect them. This was mentioned on a video here, maybe the latest one in the Michigan Tinnitus Discovery thread. (Yes, I also scored immaculate on an audiogram.)

 

FREQ is regenerating hair cells from progenitor cells with FX-322, they are not targeting the nerve with their compound. In their pre-clinical work, they have shown that the newly generated hair cells produce synaptic proteins that allow it to connect to the nerve. See slide 37 of their current investor slide deck for this:

https://investors.frequencytx.com/static-files/a2bd4cb7-38f3-49cc-902a-bb7129ef3ecd

What you're referencing is more in line with OTO-413 which attempts to re-connect nerve synapses to the hair cells that are already in place. FREQ is just growing new hair cells that connect themselves during or after mitotic process.

 

Thanks for the information Chad. I'm not a doctor or neuroscientist but it appears to me that regrowing hair cells, while an impressive feat, would then be unlikely to solve most hearing problems if Liberman's model of hidden hearing loss is accurate.

As I understand it, hearing loss results from both synaptopathy and hair cell death, with the former often happening first. Fixing the second problem without the first thus appears like a suboptimal strategy, unless I'm getting this all wrong. I imagine an ear treated with FX-322, growing some new hair cells replacing the dead ones, but with its remaining damaged hair cells and synapses unchanged.

Surely the career scientists at FREQ have considered this though? I'm hoping there's something I'm not getting right.

 

It means nothing, just that they recruited more than originally planned.

 

Considering that new hair cells that grow can take root almost like a plant with the synaptic connections, I am optimistic that we won't have to worry about that too much. If they take root in the right spot and at the right size, then hopefully that means that they could fully compensate for the task of the dead hair cell connections, to the point where the faulty synaptic wiring that presumably causes tinnitus is no longer relevant due to the new hair cells absorbing the sound.

As for the old synaptic connections themselves, I think that as long as the hair cells are still present, they can be regenerated too, in some way.

Honestly, synaptic connections have proven to be capable of regeneration in other parts of the body, from what I read in the past, and we just haven't developed to a point where we can regenerate what's in the inner ear... yet. I think that, conceptually, the synaptic ribbons are probably easier to regenerate than the hair cells themselves because of this, and if Frequency Therapeutics' treatment works as is intended, spawning new hair cells with the support cells, then hopefully it will be nothing but good news from here on out.

 

I can't say I have much interest in discussing if their strategy is suboptimal or not. You have to be able to walk before you can run. We could sit and discuss hypotheticals and theory all day long here but seeing that there are no current pharmaceutical options for hearing loss, it doesn't do us much good to debate theories on what the perfect end solution will be when we don't even have a beginning solution. FREQ has a sound strategy in my opinion and seeing that they are farthest along in clinical trials out of anyone out there, I eagerly await their upcoming trial results.

As a tinnitus sufferer with mild high frequency hearing loss, I will gladly take growing new hair cells mixed in with the old damaged ones over not being able to grow any new hair cells at all.

 

Same here! I didn't mean to come across as overly pessimistic or dismissive of Frequency Therapeutics' approach. I guess I'm just curious about the dynamics between hair cell damage and synapse damage in an ear with noise-induced hearing loss. I also hope with all my heart that their approach is successful and paves the way for treatment for our conditions.

 

Frequency Therapeutics will be holding a virtual investor event on December 13th, where they are set to review the FX-322-208 study design, among other things. Could be interesting. Is anyone on here eligible to attend?

Frequency Therapeutics to Host Virtual Investor Event, Highlighting Hearing Restoration Candidate FX-322 in Advance of Q1 Clinical Results

 

Well, they've got all their heavy hitters on the card. But what I really want to know is when is the FX-345 trial going to start. Because I don't know why else they would hold a conference now before the results of the current trial are known.

 

It's fallen.

 

I will be watching it. Anyone can register to watch. When filling out the form, just say "Retail Investor" for the company you are with.

 

Not having a command of the English language, I cannot participate. I would be very grateful if you could provide a summary. Thank you.

 

What if only synapses are damaged?

 

Then nothing happens with this drug. OTO-413 is there for that.

 

@Nobody19, but OTO-413 failed.