Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[tomytl]

According to this page:

"Anticipating 85% Reduction in Government Grants
Grants from the National Institutes of Health, the Office of Navel Research, and Oklahoma Center for the Advancement of Science and Technology made seven years of pre-clinical studies possible, and until now, HEI has had little need for traditional fundraising or donor-based programs to support the research.

We are experiencing a major paradigm shift in our revenue and expense model and are planning on an 85% reduction in grants available for research from the federal government.

As a result, we are now seeking grants from private foundations, companies, and private donors to support critical research."

But I still agree that 900k shouldn't be too difficult to obtain if their research results honestly hold "the potential to restore hearing function or reverse tinnitus disorders".

Yes it's a little strange to claim to have a cure try to raise money online whilr having licensed the technology to a pharma company. Why isn't the pharma company or Accele Bio invest if they are so certain about?
Probably someone else could write them to ask the status of development maybe they answer if it's proper English.

Hopefully I'm wrong and they handle things differently. I don't want to degrade their work or enthusiasm, but it's just my picture with the info I have.

"Otologic Pharma is pursuing additional preclinical testing of this approach in preparation for the initiation of clinical trials in humans in late 2017."

Hmmm, I can't even find this technology in the pipeline of the Otologic Pharma page.
And how is it possible, that a non profit organisation like HEI can license the technology to a company which is led by the same person?

 

[tomytl]

Hi,
here is some more informati about the REGAIN (I guess AudionTherapeutics) Trial which is starting shortly.

https://www.actiononhearingloss.org...rtunity-to-take-part-in-a-clinical-trial.aspx

 

[acufenero]

Hi,
here is some more informati about the REGAIN (I guess AudionTherapeutics) Trial which is starting shortly.

https://www.actiononhearingloss.org...rtunity-to-take-part-in-a-clinical-trial.aspx

Summary:

• Phase 1 (safety, no efficacy) starts en August. Phase 2 (efficacy) later this year in UK, Germany and Greece.
• Looking for 24 participantes aged 18-80 years with mild to moderate hearing loss (less than 10 years) who are either using or have been previously offered a hearing aid. They can have tinnitus but it can't be their main complaint.
• Treatment lasts 14 weeks: three visits, one week apart, for administration of the drug plus follow up visits to continue assessing the safety of the drug.

 

[RODRIGO]

It gives the feeling that there are many more companies about to take medications for the reversal of hearing loss and hopefully also for tinnitus. Perhaps therapeutics has much publicity to attract investment in a more competitive market than we think.It is also interesting to think that there are different drugs that can act against hearing loss, increase the likelihood of success and possibly mean that there are quite a few paths with the same result. 3 years ago it seemed much more far away ..

 

[tomytl]

I couldn't follow all comments concerning this trial. But isn't there a big unknown how this drug is working in adult cochlea? I guess, this is still the point to crack.

I just hope it does enhance soemthing even it's in a let's say 20% increase of hearing.

 

[acufenero]

I couldn't follow all comments concerning this trial. But isn't there a big unknown how this drug is working in adult cochlea? I guess, this is still the point to crack.

I just hope it does enhance soemthing even it's in a let's say 20% increase of hearing.

Yeah, their approach isn't as public as Frequency's (at least not that I'm aware of).

 

[Reinier]

I wrote them many times to ask some question considering their regeneration program but never got an answer.

I asked them about a secure way to donate (https and not http). Also no answer.
They don't seem to be very communicative.

 

[tomytl]

I asked them about a secure way to donate (https and not http). Also no answer.
They don't seem to be very communicative.

It's strange then and at least not very professional not supply https.
Anyway, I hope we are all very wrong and they have a already working solution in their lab.

 

[Coleoptere]

Does anyone know how many support cells a human has per ear?

 

[Flamingo1]

Yeah, their approach isn't as public as Frequency's (at least not that I'm aware of).

It's right there in their announcement!

The project is called REGAIN, and the drug is a Gamma Secretase Inhibitor (GSI). The REGAIN group has shown in animal studies that this class of drugs is able to turn on a chemical 'switch' to produce new hair cells from other cells in the inner ear, called 'supporting cells', and improve hearing of these animals. https://www.actiononhearingloss.org...rtunity-to-take-part-in-a-clinical-trial.aspx

 

[VRZ78]

I just hope that they will easily find participants so that they can stick with the schedule...

 

[tomytl]

I just hope that they will easily find participants so that they can stick with the schedule...

I guess yes, it shouldn't be a problem, far more common than inclusion criterias of Novartis GeneTherapy Trial.
Also the procedure seems to be standard.
Just hope for some hearing enhancement and safety....

 

[Aaron123]

You might want to look at this thread for information about the trial: https://www.tinnitustalk.com/threads/audion-therapeutics-trial.21830/ For detailed information, look at the trial registry entry http://www.isrctn.com/ISRCTN59733689

The basic approach as been discussed here countless times. Notch inhibition alone (if it works) will directly convert Lgr5+ supporting cells to hair cells.

 

[RODRIGO]

What is the difference between the audion therapeutics approach and the frecuency approach?For the human trial, Audion would use compounds developed by pharmaceutical giant Eli Lilly and with Frequency Therapeutics which would develop the treatment – using a tube or piece of foam in the middle ear to stimulate regrowth of hair cells damaged by sound

 

[tomytl]

What is the difference between the audion therapeutics approach and the frecuency approach?For the human trial, Audion would use compounds developed by pharmaceutical giant Eli Lilly and with Frequency Therapeutics which would develop the treatment – using a tube or piece of foam in the middle ear to stimulate regrowth of hair cells damaged by sound

I know it has been discussed here too, but I can't find it right now. I guess one of the main differences is that Frequemcy TX first generate supporting cell and then grow to hair cells while Audion directly convert supporting cells in hair cells.

I just concern in both methods that the position of the newly generated hair cell won't exactly be the same.

Do you guys think it's more a concept of proof trial? Or is there information about beeing able to grow hair cells in the adult mammalian inner ear?

 

[attheedgeofscience]

By not being a regular contributor anymore, I guess I am "late to the party" (re: "Frequency Therapeutics"). But for what it is worth, I am siding with the good professor (@HomeoHebbian) on this one (and hence the least popular opinion as regards companies developing inner ear restoration therapies and their potential utility towards chronic tinnitus).

As for what concerns Frequency Therapeutics, I am not sure why the general consensus seems to be that they are somehow the leading pharma company out there. For other reasons, I was asked to have a look at their pipeline just recently. Maybe I missed something during that quick review, but, as far as I could tell from their homepage (and latest publication from 2017), they only have preclinical in vitro studies to base their results on so far. Otonomy has already tested their preclinical trial compounds via an animal model and demonstrated efficacy (specifically with regards to inner ear hair cell restoration and the ribbon synapses). Here is the transcript from a conference call I attended a while back (in 2017):

Attached is also the latest presentation from Otonomy (see pages 19 & 20 for the status on OTO-4xx).

I remain skeptical regarding Frequency Therapeutics in relation to their earlier stated 18-month time frame until commencement of clinical trials. I don't see how an in vitro based discovery can advance to clinical trials (in humans) in 18 months. I also see no mention with regards to their intended delivery mechanism (i.e. how to get drug into the inner ear).

Lastly, while it is believed that the inner ear may be involved in chronic tinnitus (i.e. due to nerve fibres attached to the inner ear hair cells, or IHCs, as opposed to the outer ear hair cells, or OHCs), chronic tinnitus is likely to extend well beyond the cochlea itself.

If I were you, I would focus on Otonomy rather than FT.

 

[acufenero]

Lol.

For other reasons, I was asked to have a look at their pipeline just recently. Maybe I missed something during that quick review, but, as far as I could tell from their homepage (and latest publication from 2017), they only have preclinical in vitro studies to base their results on so far.

You may want to take another look.

I remain skeptical regarding Frequency Therapeutics in relation to their earlier stated 18-month time frame until commencement of clinical trials. I don't see how an in vitro based discovery can advance to clinical trials (in humans) in 18 months.

First, you lie on purpose in order to discredit Frequency. Then, you share a pdf with 2 useless slides and expect people to believe you. Cool.

Frequency is already trialling a first compound in humans and, of course, they'll keep working on it. Actually, a second paper is expected later this year. But okay, you can remain skeptical.

I also see no mention with regards to their intended delivery mechanism (i.e. how to get drug into the inner ear).

Definitely, you may want to take another look.

If I were you, I would focus on Otonomy rather than FT.

You don't look like an Otonomy salesman AT ALL!

 

[grate_biff]

By not being a regular contributor anymore, I guess I am "late to the party" (re: "Frequency Therapeutics").

Indeed you are!

I also see no mention with regards to their intended delivery mechanism (i.e. how to get drug into the inner ear).

Have you even looked at their web- site? As we speak they are conducting a trial in Australia on humans to monitor the amount of round-window-diffusion of their compound within the cochlea. They are conducting it on patients going through a CI.

chronic tinnitus is likely to extend well beyond the cochlea itself.

Says the guy who claim to have 50% reduction in T after SC therapy!

Are you sponsored by Otonomy?

They have actually tried their drug on animals:

"Looking at Frequency's preclinical results, Cheng notes that the company's tests on young mice got a "very robust response" but weren't as successful with adults."

 

[attheedgeofscience]

Frequency is already trialling in humans a first compound and, of course, they'll keep working on it. Actually, a second paper is expected later this year. But okay, you can remain skeptical.

Well, all clinical trials are registered with www.clinicaltrials.gov and I don't believe it is registered (FX-322). So, why don't you show me instead? How hard can be it be to share a link with a clinical trial that has started?

In addition, I have checked with my sources and hence I have confirmation that FX-322 is still in preclincal trials:

 

[grate_biff]

How hard can be it be to share a link with a clinical trial that has started?

https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372587

 

[tomytl]

Hi,
good to know Otonomy TX is also watching the regenerative segment, I hope they will release soon something about their regeneration program.

So probably we can say, that Audion TX,Frequency TX and Otonomy are close to clinical trials, that's exciting.

Maybe Decibel TX, Acousia, "Hough Ear" (OtologicTX) and Sound Pharma will follow soon.

 

[VRZ78]

By not being a regular contributor anymore, I guess I am "late to the party" (re: "Frequency Therapeutics"). But for what it is worth, I am siding with the good professor (@HomeoHebbian) on this one (and hence the least popular opinion as regards companies developing inner ear restoration therapies and their potential utility towards chronic tinnitus).

As for what concerns Frequency Therapeutics, I am not sure why the general consensus seems to be that they are somehow the leading pharma company out there. For other reasons, I was asked to have a look at their pipeline just recently. Maybe I missed something during that quick review, but, as far as I could tell from their homepage (and latest publication from 2017), they only have preclinical in vitro studies to base their results on so far. Otonomy has already tested their preclinical trial compounds via an animal model and demonstrated efficacy (specifically with regards to inner ear hair cell restoration and the ribbon synapses). Here is the transcript from a conference call I attended a while back (in 2017):

View attachment 13315

Attached is also the latest presentation from Otonomy (see pages 19 & 20 for the status on OTO-4xx).

I remain skeptical regarding Frequency Therapeutics in relation to their earlier stated 18-month time frame until commencement of clinical trials. I don't see how an in vitro based discovery can advance to clinical trials (in humans) in 18 months. I also see no mention with regards to their intended delivery mechanism (i.e. how to get drug into the inner ear).

Lastly, while it is believed that the inner ear may be involved in chronic tinnitus (i.e. due to nerve fibres attached to the inner ear hair cells, or IHCs, as opposed to the outer ear hair cells, or OHCs), chronic tinnitus is likely to extend well beyond the cochlea itself.

If I were you, I would focus on Otonomy rather than FT.

According to one of the researcher of frequency tx (can't remember the name but the post is in frequency tx thread), they already have animal efficiency data which hasn't been published yet.
The delivery method is an injection through the eardrum (same as steroids injection).
The trial that they are conducting in Australia on people receiving cochlear implant will tell us how much of the drug goes to the inner ear and if the drug is well tolerated. It's sort of a phase 1 trial.

https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372587

I think both companies show promise and Otonomy will most likely help us with their ribbon synapse reconnection.

 

[Paulmanlike]

By not being a regular contributor anymore, I guess I am "late to the party" (re: "Frequency Therapeutics"). But for what it is worth, I am siding with the good professor (@HomeoHebbian) on this one (and hence the least popular opinion as regards companies developing inner ear restoration therapies and their potential utility towards chronic tinnitus).

As for what concerns Frequency Therapeutics, I am not sure why the general consensus seems to be that they are somehow the leading pharma company out there. For other reasons, I was asked to have a look at their pipeline just recently. Maybe I missed something during that quick review, but, as far as I could tell from their homepage (and latest publication from 2017), they only have preclinical in vitro studies to base their results on so far. Otonomy has already tested their preclinical trial compounds via an animal model and demonstrated efficacy (specifically with regards to inner ear hair cell restoration and the ribbon synapses). Here is the transcript from a conference call I attended a while back (in 2017):

View attachment 13315

Attached is also the latest presentation from Otonomy (see pages 19 & 20 for the status on OTO-4xx).

I remain skeptical regarding Frequency Therapeutics in relation to their earlier stated 18-month time frame until commencement of clinical trials. I don't see how an in vitro based discovery can advance to clinical trials (in humans) in 18 months. I also see no mention with regards to their intended delivery mechanism (i.e. how to get drug into the inner ear).

Lastly, while it is believed that the inner ear may be involved in chronic tinnitus (i.e. due to nerve fibres attached to the inner ear hair cells, or IHCs, as opposed to the outer ear hair cells, or OHCs), chronic tinnitus is likely to extend well beyond the cochlea itself.

If I were you, I would focus on Otonomy rather than FT.

Hi, do you know it this OTO-311 is targeted for chronic tinnitus or just acute? I know you had a call about AM-102 again only being for acute again...

 

[attheedgeofscience]

Have you even looked at their web- site? As we speak they are conducting a trial in Australia on humans to monitor the amount of round-window-diffusion of their compound within the cochlea. They are conducting it on patients going through a CI.

Well, according to that trial registry, it is not enrolling yet...

...and it was meant to have started enrollment already some two months ago. Actually, it is scheduled to finish in a month from now.

So... I will stand by the fact that I consider the trial to still be at the preclinical trial stage (but, I am happy to be proved wrong - in fact, I would love to...!).

I realize my opinion may not reflect the populist view, but, we are all different, right...? And, I would - for a number of reasons - still consider Otonomy to be the safer bet.

 

[FIGHT]

Hi. Assuming all the trials From Frequency therapeutics,audion and novartis are all successful. Do you think we can have a cure/help within five years? How much it will cost? I'm saving all my money for this.

 

[attheedgeofscience]

Hi, do you know it this OTO-311 is targeted for chronic tinnitus or just acute? I know you had a call about AM-102 again only being for acute again...

The only thing I know is that OTO-311 is expected to move ahead with a phase-II trial in the 2nd half of 2017. Otonomy decided to have a "pause" while figuring out the "collateral damage" (if any) from the AM-101 trial. But, they are confident with their programme (they have since stated).

There is the Wenzel study which used Gacyclidine in high doses under ideal conditions (direct access to the cochlea) but the outcome was not especially impressive (small scale study with high degrees of deafness - which may have contributed). So, I would expect Otonomy to play it safe and get good data from an acute-stage patient population (during phase-II), and if all goes well (which I think it will), then they will do some exploratory testing in phase-III.

My thoughts, at least.

 

[attheedgeofscience]

You don't look like an Otonomy salesman AT ALL!

Hmmm... do I look like an "Otonomy salesman" any more than the rest of you (especially yourself) look like "FT salesmen"?

Considering a certain background I have had with a particular liaison between TinnitusTalk and "some pharma company", the notion that I should be affiliated with Otonomy is hilarious. But you would have to know a little history of tinnitus to understand the underlying dynamics in that regard.

 

[Paulmanlike]

I thought that once the tinnitus passed acute stage - it was then established into the brain and blocking these NMDA receptors would be too late - I got this impression from the Auris trials and their website, stating a cure for chronic tinnitus does not seem likely.

And I think OTO's approach is again blocking NMDA receptors so I would have assumed it will only work for acute tinnitus (if it works at all)

 

[grate_biff]

for a number - of reasons still consider Otonomy to be the safer bet.

You are entitled, but I don´t see how Otonomy´s approach will differ from FTX regarding how "chronic tinnitus is likely to extend well beyond the cochlea itself."

Maybe Homohobbyist is right though, that a neuro-drug working more directly on the brain is the better approach and that the brain will have difficulties "unlearning" T even though input is restored.

I think that maybe electro-convulsive -treatment would be our best bet to jolt our brain back to scratch
Or a good nights sleep!

Kind of funny(in a good way) that we now are discussing who will supply us with the best treatment, rather than the same old bullshit.

Think we all can agree, this is a good sign!

 

[tomytl]

Salesman or not Salesman, doesn't matter, there is nothing to sale at the moment. I welcome all point of views and informations about running or ongoing trials. Everthing is speculative before tests show us positive results.