Frequency Therapeutics — Hearing Loss Regeneration

I wonder if getting treated with say Audion's REGAIN first, alters the inner ear in such a way, that you're not able to have FX-322 afterwards? And vice versa.

 

That's what I'm worried about.

 

I have a feeling that REGAIN will make their announcement first. Hopefully, it will be what we all want to hear. However, before REGAIN's meds hit the open market, FX-322 will probably have made their announcement. My plan is make the decision once I hear the results of both.

 

I hope they will tell us more about the improvements in hearing that they mentioned in April!

 

I'm speaking on as to how their respective drugs worked in the lab. Frequency Therapeutics is trying to expand the number of LGR+ progenitor cells and then converting those to hearing cells using additional drugs in their cocktail. Regain is not doing any sort of expansion. Both utilize a gamma secretase inhibitor, although different formulations, to cause the conversion to hair cells. Thus why I stated they are different and I suspect FX-322 should yield better results based on their research noted in their paper due to them being able to increase the population of LGR+ progenitor cells to convert. Time will tell...

https://www.cell.com/cell-reports/fulltext/S2211-1247(17)30136-5

 

Do any of these drugs work for hidden hearing loss?

It seems that OTO-413 targets hidden hearing loss.

 

Do any of you sign up to get email updates from Frequency Therapeutics?

 

I think we should not be worried. It will be pioneering in either case, any big improvement will be welcome. I think seeking perfection in the beginning of the regeneration movement may be asking too much. Let's say we recover enough hearing to notice it significantly and we enjoy a reduction in tinnitus that's significant... that would be so much to be thankful for.

If I regained some hearing and had a quieter and more manageable tinnitus I'd be overjoyed. By more manageable, I mean not notice for long periods of time, the kind that is fairly easy to habituate to and is not nasty, loud, and intrusive. More hearing would hopefully reduce tinnitus, but would also make life more enjoyable for obvious reasons. Conversation, listening to the world, music, nature.

Let's not fret too much about perfection, let's have lower expectations and assume same stringent rules about protection and preservation. This is all new, no guarantees or even knowledge of what would happen to a patient in ten years after therapy. It's never been done before.

Fingers crossed these confident scientists have got this... and the coming trials reap good news. We are not out of the woods yet... inside I fervently pray in my own way for what would be a modern miracle - hearing regeneration... it's a big ask... but science has and will do things inconceivable... there are many examples of this in our daily lives, be it flight, computers, telecommunications, modern surgical techniques... etc...

Hope we get lucky, and greed and good will motivates these companies to move fast.

 

They will have to move fast because REGAIN and Frequency Therapeutics are in Phase 2. There will definitely be competition between the two on who releases the drug first. If they both release it around the same time price will definitely be a factor.

 

Wrong, American regulators won't allow Frequency Therapeutics to launch it first. Bet your money on REGAIN.

 

Any idea about whether this might help tinnitus in cases where there's no measurable hearing loss?

My right ear has substantial hearing loss and can probably benefit from FX-322 but my left ear likely has hidden hearing loss or whatever but it still has tinnitus...

If it does come to market, hopefully I can convince an ENT that I need it in both ears lol.

 

I'm not an expert on this but I would assume both ears would have some level of hearing loss since not many places test above 8 kHz, so I reckon both ears will benefit from FX-322.

 

Hopefully (optimistic) it will be available in 5 years or so.

What do others here think?

 

Given the risk profile of such medication, I imagine people wouldn't inflict it to an ear that has no indication of being unhealthy.

Many of us live with imperfect ears, and in fact, all of those we think of as people with "healthy ears" do have some amount of hearing degradation as they've aged. That doesn't mean they should go and get treatment to "recover heir hearing": for them, the risk is likely to dwarf the reward.

My philosophy is: "If it ain't broke, don't fix it!"

 

Understood. Still even if the people in the studies all had hearing loss below 8 kHz it would be useful if Frequency measured the before and after hearing both above and below 8 kHz.

 

A hair cell is a hair cell and there is no fundamental frequency response difference between cells. However, the location within the cochlea determines its frequency response. The outermost cells being the highest frequency and the most inner being the lowest. I don't think there is any reason to not believe there wouldn't be a high frequency improvement if it really causes hair cells to regenerate as long as there are LGR+ support cells still intact.

 

Could this potentially make hyperacusis patients worse or better?

 

We are assuming it would make them better, but more hair cells means more sound so it could make it worse. No one really knows.

 

Potentially, better. But all we can do now is speculate. We don't even know if the drug works at all as it's intended. And even if it does we still don't know if it will help people with tinnitus and/or hyperacusis. But restoring damaged hearing should potentially help with both tinnitus and hyperacusis.

 

That's what I was thinking. The more hair cells you have, the louder it will be but then what happens if those hair cells that get regenerated somehow get reconnected to the synapses which therefore does cure hyperacusis, tinnitus and hearing loss.

 

I don’t think that more hair cells make sound LOUDER.

I suspect more (connected) hair cells produce a more nuanced, more detailed sound. For the simple fact that you get input from all the frequencies.

My gut feeling (no more than that) tells me that hyperacusis has more to do with nerve damage... (did you ever get an exposed nerve in a tooth cavity?)... or with the brain turning up the volume, looking for a signal.

Reconnecting the nerve may or may not fix it. Restoring input of a signal may or may not fix it. We will have to wait to know for sure.

 

New hair cells make external sounds louder. Hearing loss is measured in dB. We lose dB. New hair cells will get you more dB in whatever frequency it is restoring.

The problem is that tinnitus and hyperacusis are more complex than we all realize. I've learned through the forums that not everyone that has hyperacusis has it for the same reasons. Same goes for tinnitus. I guess we will see what happens as we progress in the trials and it is possible that some people might be helped while others aren't.

 

Perhaps something else will happen. I read that most prone to damage are outer hair-cells. Outer hair cells "regulate" dynamics of the sound as I understand. Perhaps therefore regenerating that damaged part will give back the dynamics?

 

Healthy hair cells = no hyperausis.
Damaged hair cells = hyperacusis and tinnitus.
Regrown hair cells = less hyperacusis and tinnitus.

 

Why wouldn't regrown hair cells completely eliminate tinnitus?

 

We don't know for sure but I really hope it cures tinnitus, hyperacusis and hearing loss.

 

There is still a question as to how effective this treatment is going to be. It's my opinion that you need to get back to baseline or very close to it for the tinnitus to go away. Regrowing hair cells should make it quieter. They haven't discussed how effective the treatment is but they have discussed multiple doses which means that a single dose regrew hair cells but not enough to get the subjects back to perfect hearing.

It is possible. If this is true then it could help. So we are saying that improving hearing would make sounds softer since hyperacusis is amplifying them in an unnatural way...

 

It's possible that regrown cells don't attach to a nerve and if they do regrown cells might perform worse than cells you're born with. Yes birds and zebra fish regrow hair cells but for them it's a normal mechanism. In mammals when hair cells die off there is scarring forming in those areas which could make regenerated cells less functional.

 

Thanks for the optimism... that really helps... cheers Silvio.

 

We know that for at least two out of a small number of participants in the last FX-322 trial, at least some regrown hair cells were bound to the neural pathway. That's something.

He answered Street Novelist's question. That's all. There's nothing in his answer that should kill anyone's optimism.