Frequency Therapeutics — Hearing Loss Regeneration

Well, the approach is different, and may I say more "promising" in this one. Unlike the Genvec method, the Frequency method tries to trigger and facilitate a natural process already present in the mammalian ear for regenerating the inner-ear cells. This process is the same process which formed your inner ear during the embryonic state, it just became dormant once the full inner-ear was formed. In birds, this process seems to stay active, giving them the ability to recover from hearing damage. This was an important discovery leading to this approach.

One could argue triggering this natural process again might also be safer than what Genvec did. Genvec's delivery method was invasive (making a hole in the cochlea) and they didn't make use of the natural process described above, which increases the chance of uncontrolled growth among other potential problems. The Frequency method appears to use round-window diffusion by tympanic injection. In my opinion it is preferable to stay close to what nature does and minimise invasiveness. Nature usually does these kind of things better than we can (at least currently).

We have to see how Frequency's method will turn out, but I have to say I am excited.

 

Exactly for that reason I have wondered if there is a possibility that correct hair cells (length/inner/outer hair cell) and their subsequent location in the cochlea is "taken care of" by this natural process. The supporting cells (was it supporting cells with LGR5 marker?) that are instructed to differentiate are already at the correct location. I wonder if the support cell will only differentiate if the adjacent hair cell is damaged/gone.
Is this process getting close to processes in inner ears of birds after damage?

 

I am one of the people that benefit greatly from HAs. As far as I know I only have hair cell damage due to genetic factors. I have posted many times, but I can take out my HA and within 5 minutes my T will go from a 1 to a 6. I put it back in and let natural sounds enter and its back to a 1. The brain is very plastic and assuming your T is due to hair cell death, I have a strong feeling hair cell regeneration will cure T or at least help it greatly.

I also have another theory on people that have hearing loss but no T. They have T, they just don't realize it, just like I didnt realize it today until I got on this forum. My HA's also kept it at bay all these years until I had anxiety and stress and it got loud. Once it found me the best I can do is get it to a 1 or 0 if I am not aware and my mind concentrates on something else.

I'm pretty excited that this would be a cure for T for people that just have hair cell damage, assuming you can get 100 percent of your hearing back. At a min it could take a 6 to a 1 or a 2. After you have had intrusive T (10), living with T at a level of 1 is like a vacation and I could be extremely happy with that.

 

Do your hearing aids reduce it from 6 to 1 even in a quiet environment e.g. In bed? Or do they just help when out and about as you are able to hear external sounds better?

 

It makes sense to start with the cochlea. One the cochlea and hearing is fairly self contained so a treatment to it wouldn't necessarily impact other parts of the body. That is not true for treatments to the brain and thus makes those drugs a lot hard to target.

I really hope Frequency has very clearly defined results (preferably in the positive) because very slight improvements to hearing (5-10 dB) might not be able to definitively confirm the link between hearing and tinnitus. A large improvement say 50 dB of gain in hearing threshold in the Frequency trial would put this question to bed.

 

Yeah I mean I have lower hearing loss noise notch and also have high frequency hearing loss due to ear infection. So hearing aid did not help me. My loss from ear infection is 30 db and noise notch is 25 db go figure right.

 

Let me get this right then, I will go for a hearing test (as still unaware if I have a hearing loss) but I have a low frequency tinnitus between 1000- 2000khz, and if I do have a mild loss because I would of noticed a moderate loss, a hearing aid might help my tinnitus?

And what do we mean by helping tinnitus? Does that mean by masking with external sources or would the reduction in volume also be present in quiet setting (in bed)?

Sure I heard something that not only a hearing aid helps u more aware of outside sound but it increases acoustic stimulation in the frequencies you lost and helps tinnitus reduce that way?

 

I think Frequency would know the answer to this question. I agree they likely can't control this process but they would have been able to view its effects.

 

Very good question. As far as I am informed at this point, Frequency's method aims to trigger the same natural cascade of events which happened during the embryonic stage. Whether this also acts favourably in case of a cochlea where only certain parts are damaged, remains to be seen. In birds, which apparently are able to recover from a partially damaged cochlea, this appears to be the case. This might indicate something positive, but it is yet to be determined in humans. You might find the following interesting though in relation to this.

Studies in 2014 found the molecule Bmp7 present in mammalian inner ears during development. This molecule seems to play a role in developing hair cells specialised in lower frequencies, because when exposed to this marker, both hair cells at low- and high frequency locations started showing characteristics of low-frequency hair cells. The concentration of bmp7 in the high-frequency locations of the cochlea appears lower than in the cochlear apex, where the lower frequencies reside. The expectation is that the gradual reduction of the concentration of Bmp7 plays a role in the frequency-tuning of the hair cells. The concentration appears highest near the hair cells responsible for the lower frequencies, as to be expected, and gradually becomes lower when the frequencies increase. Another signaling molecule, called "retinoic acid", appears to help with the correct tonotopical organisation and pattern of the hair cells. The studies are linked below.

Studies:
https://www.ncbi.nlm.nih.gov/pubmed/24845721
https://www.ncbi.nlm.nih.gov/pubmed/24845860

And a nice explaining article here:
https://www.nih.gov/news-events/nih-research-matters/hearing-different-frequencies

Surely there are more molecules involved for specific locations in the cochlea and hence for developing frequency-dependent types of hair cells with their own characteristics. It would be nice if Frequency's approach triggered the naturally present infrastructure of these molecules and replenished hair cells where needed, as this would prevent the need to specifically know each molecule individually and it's working before we can get to any reasonable treatment. It could provide a shortcut to something usable as a treatment while the rest of the molecules are being figured out (I believe Decibel Therapeutics aims to do this more thoroughly). Ultimately the better we know all the molecules involved, the more effective and targeted the treatments can become, of course.

Like @Samir said above, identifying the specific damaged frequencies, the specific molecules for treating them and escorting those to the right place (if this does not happen due to some natural process) in the cochlea is a much more advanced task at hand. Let's both hope Frequency's method is able to repair a partially damaged cochlea without malicious side-effects and that it's at least effective till some extend. It would make for a minimally invasive treatment requiring less knowledge. But let's not forget; during the embryonic state the cochlea is formed from scratch. The outcome with a partially damaged cochlea is perhaps different (short term or long term). There are still quite some uncertainties here.

 

The hearing aides help in quiet environments as well. It is never truly quiet though.

A hearing aide might help your tinnitus. It is not always the case though. By help, it actually lowers the volume of the tinnitus, it doesn't just mask it. Yes, by increasing volume of the lost frequencies it basically gives you normal hearing again and the brain senses this and cuts the sound. Once the cochlea is fixed, the brain no longer produces the phantom sound. In this case the hearing aides provide the missing frequencies.

If you had a bad stressful day, took some nicotine, caffeine, had some anxiety and maybe depression, the hearing aides won't do anything.

Agreed, there are some uncertainties, but as you mentioned previously, it works for the birds so there is hope that this can work for humans as well. I guess at this point we are hoping the cochlea just fixes what needs to be fixed, because if someone has 0 loss at 500hz and it boosts that level to plus 50db, then that would probably give you something similar to H at those frequencies which could be quite unpleasant.

 

Hey hate to be Debbie downer but spoke with heart transpalant resident and asked him about progenitors cells and heart repair he said hey are dangerous right now in studies they can't control them turn in to tumors. He said it would be really cool to heal your heart. He said 10 years. Never asked him about repairing a ear. Good news he thinks that treatment is hopeful for the heart. I am hopeful for the ear.

 

As I posted earlier, at least in the GI tract, lgr5+ cells serve as cancer stem cells: http://www.nature.com/nature/journal/vaap/ncurrent/full/nature22081.html

 

Interesting. Being somebody who suffers tinnitus with no noticeable loss of hearing, I'm curious if one may help me. I guess I'll see if I have a loss first, but I wonder if they would give me one if it's only minor as otherwise I hear fine?

On my research I was under the impression they only help by making you more aware of external sounds. However @carlover has noticed his tinnitus decrease in quiet settings as well.

I'm sure my audiologist has said that it can help too something about stimulating the lost frequencies.

I guess this will be next avenue in attempting to reduce it. It's night time that bothers me the most, any reduction would be a blessing.

 

I am talking about out of the range what they don't test on standered audiogram. Like around 16 hz I have 30 db loss hearing aids won't help.

 

"Here, we demonstrate that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues."

I think its actually referring to LGR5+ in already form colorectal cancer not the one present in normal colon and rectum tissue. Just my interpretetion.

 

Not sure if this has been posted sorry if it has been.

Trial to Reverse Deafness To Begin in 2019 -...

 

A bit more good news. I got in touch with Will McLean and asked him:

The findings that have been published so far involve cochleae removed from mice, primates and a human. I see that in 18 months there will be live human trials. Has there/will there be data from live animal experiments prior to that?

He answered:

We have promising animal data

 

Isn't this what all researchers say?

 

I'll take it lol

 

You know when noise damages our ears and we end up with tinnitus, the most delicate part are the nerve fibres, and are usually damaged before any hair cells (according to my research) this forms as "hidden hearing loss". So are frequency attempting to repair these nerve fibres and not just regenerate hair cells? Or would repairing hair cells go on to form healthy nerve fibres?

Not as up to date here so please shine some light.

 

http://www.businesswire.com/news/ho...am-Strengthened-Executive-Level-Hire-Internal

More news

 

Excellent. They're the real deal

 

You seem to know much about the reascerch scene in this so could I ask you how optimistic are you about a cure if I can call it that for hearing and maybe tinnitus. I got tinnitus in March and didn't think I had a hearing loss as time goes I have been suspecting that I may have it after all. So how long away if ever do you think a cure or something that will help is?