Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[IreneO]

Really informative. Thanks @Aaron123

 

[grate_biff]

Very informative and kind of hope-giving stuff you presented there. Thanks @Aaron123

Btw. The fact that you love/loved Ian C. also makes you very likable in my book

 

[jeff W]

Could you elaborate on that? Are you saying that companies like Frequency could apply for CIRM grants if they chose to move their business to California?

PLEASE LET US GIVE YOU MONEY SO THE STATE DOESN'T CUT OUR FUNDING!

 

[FIGHT]

An update on companies involved in HL research (not just regenerating hair cells): https://www.biocentury.com/biocentu...6-02/how-hearing-loss-became-investable-space I don't have a subscription so I haven't read the entire article. Of note is the graphic. What follows is a quote from Figure 1

"The majority of hearing loss programs have anti-inflammatory and/or anti-apoptotic properties that aim to prevent hearing loss or stop it from progressing. Some of these, such as brimapitide from Auris Medical Holding AG (NASDAQ:EARS) and Otividex dexamethasone otic gel from Otonomy Inc. (NASDAQ:OTIC), are exploiting advanced delivery technologies that should reduce treatment burden and improve efficacy over off-label steroids.

At least two in this category, SENS-401 from Sensorion S.A. (Euronext:ALSEN) and AF243 from Affichem S.A., may also promote repair of axons and synapses. Compounds in the otoprotective category below protect sensory neurons by other types of mechanisms.

At least nine companies aim to reverse hearing loss that has already occurred by regenerating lost hair cells or synapses. The only regenerative program in the clinic is CGF166, a gene therapy from Novartis AG (NYSE:NVS; SIX:NOVN) and GenVec Inc. (NASDAQ:GNVC) that uses a recombinant adenovirus 5 (Ad5) vector to deliver the atonal homolog 1 (ATOH1; HATH1) transcription factor. Acousia Therapeutics GmbH, Audion Therapeutics B.V., Decibel Therapeutics Inc., Inception 3 Inc., Otologic Pharmaceutics Inc. and Otonomy each have undisclosed regenerative therapies in preclinical development not shown below.

Autifony Therapeutics Ltd. is the only company targeting the CNS component of hearing. AUT00063 modulates potassium channels in the brain to enhance central auditory processing.

The chart includes lead indication for each program. Those not specifically noted with "prevent" are intended to treat their respective indications. (A) Spiral Therapeutics Inc. has an option to BN201 and BN119 for inner ear disorders and anticipates making a decision by 3Q17; (B) GenVec Inc. is being acquired by Intrexon Corp. (NYSE:XON); (C) Phase I/II ongoing; JNK = c-jun N-terminal kinase; LXR = liver X receptor; PGF2 alpha = prostaglandin F2 alpha receptor; NFE2L2 = nuclear factor (erythroid-derived 2)-like 2 (NRF2); PPAR = peroxisome proliferation activated receptor; KCNC1 = potassium channel Kv3.1; APAF1 = apoptotic peptidase activating factor 1 (APAF1); SGK2 = serum/glucocorticoid regulated kinase 2; CDKN1B = cyclin dependent kinase inhibitor 1B; Source: BCIQ: BioCentury Online Intelligence, company press releases, company interviews

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What if FDA pass new regulation for clinical trial. Can we expect novartis-genvec sooner?

 

[friend]

I have reliable information that Chloe Sohl who was treated by RNL Bio for hearing loss, also suffered from tinnitus. Both conditions were improved significantly in her case. She was treated using her own cultured stem cells. The youtube link can be found in my journal. There is no need to wait ten years for a cure.

If this forum requires proof that she also suffered from tinnitus (which is not described in the published RNL video on youtube), I can probably find a way to contact her or her parents (who are both doctors) via my "back office channels". But again, I have reliable information that this is the case...

There are also two MS patients who have cured of tinnitus (as a secondary symptom) using stem cells.

I had stem cells recently. With great disappointment and cost it didnt work on me.

 

[Tinker Bell]

I had stem cells recently. With great disappointment and cost it didnt work on me.

In the US through one of the rearch companies we have been discussing? Were they injected in your ear or via IV into your bloodstream?

 

[grate_biff]

I had stem cells recently. With great disappointment and cost it didnt work on me.

Got it!

 

[Aaron123]

What if FDA pass new regulation for clinical trial. Can we expect novartis-genvec sooner?

I'm not sure what regulation you are referring to. Whatever it is, I don't believe it will help Genvec. Their problems are with recruitment. Beyond that, if you read the Genvec thread, some of us, myself included, are skeptical that their approach is going to work.

 

[Mentos]

I'm not sure what regulation you are referring to. Whatever it is, I don't believe it will help Genvec. Their problems are with recruitment. Beyond that, if you read the Genvec thread, some of us, myself included, are skeptical that their approach is going to work.

@Aaron123 and in your view which approach has the biggest chance of success in treating T, Frequency TX or Decibel TX?

 

[Paulmanlike]

@Aaron123 and in your view which approach has the biggest chance of success in treating T, Frequency TX or Decibel TX?

I would of thought decibel - because they mention specifically about treating tinnitus and not just hearing loss. They are also focused on repairing the synapses - these are more vulnerable to damage caused by noise and should be easier to fix from what ive read.

 

[Rubenslash]

I would of thought decibel - because they mention specifically about treating tinnitus and not just hearing loss. They are also focused on repairing the synapses - these are more vulnerable to damage caused by noise and should be easier to fix from what ive read.

Those activated progenitor cells from Frequency also have synapses so they could compensate for the loss from your older hair cells, no?

 

[Aaron123]

Aaron123 and in your view which approach has the biggest chance of success in treating T, Frequency TX or Decibel TX?

Hmm. Good question.

We know more about what Frequency is up to. Given that some people who get hearing aids see a reduction in tinnitus, assuming Frequency's treatment "works", it seems likely that at least some people who receive treatment will see a reduction in tinnitus. I have no idea what fraction of people might be helped or how much they might be helped.

We know much less about what Decibel is working on specifically. My guess is that they are taking two broad approaches. One of these is similar to Frequency in the sense that they are taking existing science and attempting to develop treatments sooner rather than later. Seems likely that this involves neurotrophins to treat synapses, but I don't think we know this for certain. We also don't know with certainty that this will help tinnitus. Liberman and co-authors have shown increased firing rates for the surviving neurons/synapses and suggested this may be related to tinnitus. This seems to make sense, but it hasn't been proven. (The second part of their strategy - which is different than Frequency - is to start with the basic science and work from there. Not so relevant at this point as this will take a long time.)

So based what what we know I guess I give the near term edge to Frequency, but this is largely due to a bit better information and could change tomorrow with some new news from Decibel.

The bigger problem is the research that shows that tinnitus results in changes throughout the brain. I'm hopeful that plasticity works in reverse, but I am not aware of convincing evidence of this regarding tinnitus.

Probably not a very satisfying answer.....

 

[friend]

In the US through one of the rearch companies we have been discussing? Were they injected in your ear or via IV into your bloodstream?

US, thru IV.

 

[Paulmanlike]

Hmm. Good question.

We know more about what Frequency is up to. Given that some people who get hearing aids see a reduction in tinnitus, assuming Frequency's treatment "works", it seems likely that at least some people who receive treatment will see a reduction in tinnitus. I have no idea what fraction of people might be helped or how much they might be helped.

We know much less about what Decibel is working on specifically. My guess is that they are taking two broad approaches. One of these is similar to Frequency in the sense that they are taking existing science and attempting to develop treatments sooner rather than later. Seems likely that this involves neurotrophins to treat synapses, but I don't think we know this for certain. We also don't know with certainty that this will help tinnitus. Liberman and co-authors have shown increased firing rates for the surviving neurons/synapses and suggested this may be related to tinnitus. This seems to make sense, but it hasn't been proven. (The second part of their strategy - which is different than Frequency - is to start with the basic science and work from there. Not so relevant at this point as this will take a long time.)

So based what what we know I guess I give the near term edge to Frequency, but this is largely due to a bit better information and could change tomorrow with some new news from Decibel.

The bigger problem is the research that shows that tinnitus results in changes throughout the brain. I'm hopeful that plasticity works in reverse, but I am not aware of convincing evidence of this regarding tinnitus.

Probably not a very satisfying answer.....

"I'm hopeful that plasticity works in reverse..."

According to the work of ACRN therapy it is possible to change the brains plasticity reducing tinnitus. Again, whether that is true or there's been much evidence for this is another topic.

 

[Flamingo1]

Dr . Albert Edge, one of the founders of Decibel Therapeutics, demonstrated the regeneration of hair cells in 2013, so who knows what Decibel is up to.

www.medicalxpress.com/news/2013-01-sensory-hair-cells-regenerated-mammal.html

 

[Paulmanlike]

Dr . Albert Edge, one of the founders of Decibel Therapeutics, demonstrated the regeneration of hair cells in 2013, so who knows what Decibel is up to.

www.medicalxpress.com/news/2013-01-sensory-hair-cells-regenerated-mammal.html

Probably filing for bankruptcy

 

[jer]

Why would u say that?

 

[Paulmanlike]

I'm only joking (I hope not!)

 

[jer]

Ah, thank you! You gave me half a heart attack. Haha

 

[RODRIGO]

It is very possible that changes in the entrance of more sound implies diminution or disappearance of tinnitus, as it happens in many cochlear transplants.

 

[Mentos]

It is very possible that changes in the entrance of more sound implies diminution or disappearance of tinnitus, as it happens in many cochlear transplants.

On the other hand we know from some CI users that the implant can exacerbate tinnitus or induce tinnitus in the indvidiuals who were previously tinnitus free.

 

[Iliasp]

Off course because it is quite invasive uppon placing

 

[RODRIGO]

Cochlear transplants can seriously affect the auditory nerves. Most tinnitus improves, they may not be very well implanted ...

 

[RODRIGO]

I think there are tinnitus, although they are represented in the auditory cortex, are continually feeding on problems in the cochlea. There are studies in which once cut the auditory nerve 50% of tinnitus disappeared. It may not be the same as the tinnitus generated by ciliated cells in poor condition than the tinnitus generated by damaged auditory neurons

 

[FIGHT]

I had read news, It says that Pres. Trump wanted faster approval of drugs. I`m thinking if FDA will cut regulations. We can expect genvec product sooner.

I'm not sure what regulation you are referring to. Whatever it is, I don't believe it will help Genvec. Their problems are with recruitment. Beyond that, if you read the Genvec thread, some of us, myself included, are skeptical that their approach is going to work.

 

[Flamingo1]

Does anyone know about the Audion Therapeutics approach? Do you think that company's approach is as promising as Frequency's and Decibel's? I understand they are in or near clinical trials.

 

[VRZ78]

Does anyone know about the Audion Therapeutics approach? Do you think that company's approach is as promising as Frequency's and Decibel's? I understand they are in or near clinical trials.

They are in clinical trials, recruitment starts in September, check out the thread for details.

The main difference is that Audion approach directly converts supporting cels into hair cells, instead of making the supporting cells divide first and then make then turn into hair cells.

 

[Flamingo1]

The main difference is that Audion approach directly converts supporting cels into hair cells, instead of making the supporting cells divide first and then make then turn into hair cells.

This is great news! Audion's trial will potentially provide us with info as to whether Frequency's approach will work.

 

[Paulmanlike]

So we've got one company Genvec already in clinical trials and Audion to start in September with them publishing results in Jan 2020.

My hope is that these approaches will cure tinnitus regardless of hearing loss or not.

 

[Aaron123]

Does anyone know about the Audion Therapeutics approach? Do you think that company's approach is as promising as Frequency's and Decibel's? I understand they are in or near clinical trials.

There is a thread about their trial:
https://www.tinnitustalk.com/threads/audion-therapeutics-trial.21830/

Given what we know about their approach (only Notch inhibition), their approach is inferior to Frequency's approach. Notch inhibition alone causes supporting cells to directly differentiate resulting in the loss of supporting cells which may or may not be a problem. More concerning, following the initial positive results, later results have been more mixed in terms of the success of generating hair cells using Notch inhibition alone.

We don't know what Decibel's lead approach is going to be so there is no way to compare it.