Frequency Therapeutics — Hearing Loss Regeneration
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HootOwl
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- Feb 14, 2020
- 1,630
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- 1-2019
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- 20+ Years of Live Music, Motorcycles, and Power Tools
Very interesting... I need to get this done... just curious.. do you experience tinnitus that matches the ranges where the losses are present?
Thuan
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- Jul 5, 2020
- 221
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- Ear infection right ear 2018. Sound trauma left ear 2020.
@FGG and anyone else, https://www.cell.com/cell-reports/fulltext/S2211-1247(17)30136-5), under Results in section "Conversion of Lgr5+ Cells to Hair Cells" of the second paragraph:
"Expansion using EFICVP, followed by differentiation with LYC, produced the maximum number and purity of hair cells..."
I gather from that it means they needed to first establish a healthy population of support cells (because previous studies were unsuccessful when working with low population of support cells) and THEN induce them to differentiate to hair cells.
If that's the case, wouldn't a single intratympanic injection (with both medium in one shot) be ineffective? If they activate clonal expansion of support cells and differentiation at the same time, then it would not give enough time to establish a healthy support cell population to maximize hair cell regeneration. Anyone who studied biology knows that eukaryotic mammalian cells take around 24 hours to complete mitosis.
Shouldn't a first injection be given first to induced healthy support cell expansion and then a second injection at a later date to induce differentiation? That seems obvious, no? Or am I missing something while reading that article?
"Expansion using EFICVP, followed by differentiation with LYC, produced the maximum number and purity of hair cells..."
I gather from that it means they needed to first establish a healthy population of support cells (because previous studies were unsuccessful when working with low population of support cells) and THEN induce them to differentiate to hair cells.
If that's the case, wouldn't a single intratympanic injection (with both medium in one shot) be ineffective? If they activate clonal expansion of support cells and differentiation at the same time, then it would not give enough time to establish a healthy support cell population to maximize hair cell regeneration. Anyone who studied biology knows that eukaryotic mammalian cells take around 24 hours to complete mitosis.
Shouldn't a first injection be given first to induced healthy support cell expansion and then a second injection at a later date to induce differentiation? That seems obvious, no? Or am I missing something while reading that article?
- Feb 6, 2020
- 971
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- 11/2019
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- Noise
What are these results suggesting? Sorry, not really familiar with reading audiograms.
HootOwl
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One of my tones is a high frequency hiss, but interestingly enough it matches to around 13,200 Hz or so, not 16,000 Hz. When I sweep test that specific frequency completely dips out, and then starts back up again about 50 Hz later.
Also, despite acquiring many reactive tones, my audiogram has not changed at all. The notches for my reactivity (and normal tinnitus) only reveal themselves during sweeps.
I'm a firm believer that audiograms are wonderful tools for diagnosing widespread outer hair cell damage (for hearing aids), conductive loss, Meniere's, and flat epithelium - but are terrible for detecting mild to moderate damage at highly selective frequencies.
So when people say they have no hearing loss, I think they misunderstand how truly limited audiograms, even high frequency ones, really are for detecting damage at a specific tinnitus tone.
Isn't the multiple dosing theory being tested in the current trial phase?
Thus why are they examining the effect(s) of two or four injections as opposed to a single injection to understand how people respond to the treatment with multiple doses of the drug.
HootOwl
Member
The way I interpret it is that I don't have profound loss at any point in my ultra high frequencies, so if my hissing tones are due to OHC death, then FX-322 should be able to help me, since my support cells are still more or less intact.
HootOwl
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I suppose I can! Although past 16 kHz the sounds get kinda weird... instead of a pure tone you hear a static bssst. It's really easy to make out during the test.
Thuan
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- Jul 5, 2020
- 221
- Tinnitus Since
- 05/2018
- Cause of Tinnitus
- Ear infection right ear 2018. Sound trauma left ear 2020.
@HootOwl Those are very informative audiogram results. Thanks for posting it. Your overall hearing is so good at 0 dB, except for the ultra high frequencies. I'm at 10 dB for most frequency except 4 kHz and 8 kHz at 15 dB. I'm actually kind of scared to take an extended audiogram. If I am completely deaf at a certain frequency, then it's quite hopeless for me.
That flies in the face of most of what they teach about hearing, that's what impressed me. Well done on keeping good hearing, bad luck on the tinnitus bit.
Thuan
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- Jul 5, 2020
- 221
- Tinnitus Since
- 05/2018
- Cause of Tinnitus
- Ear infection right ear 2018. Sound trauma left ear 2020.
If you look at Figure 4a under the quoted paragraph, they're listing not by concentration but by different combination of grow factors (which affects mitosis of the support cells or differentiation to hair cells). They're including different factors and the order of it, such as using EFICVP to induce mitosis and LYC to induce differentiation from their sentence "Expansion with EFICVP and differentiation with LYC..."
Edit: In other words, the researchers were trying to find the optimal growth factors and by their description of their methods they established first a healthy amount of support cells starting from low count before they induce differentiation.
What I am confused about for the injection, for human trials, is that a single cocktail with both growth medium will start the process simultaneously without giving time to establish a healthy population of support cells. Perhaps there was something I'm missing in reading this article somewhere else?
HootOwl
Member
Don't be scared! I have 5-10 dB loss at many of my frequencies on my 8 kHz audiogram also.
It would be very unlikely that you would suddenly dip to profound at your UHF with mild lower frequency loss such as that.
HootOwl
Member
I got tinnitus at 18, so at a time when people were starting to party and club I was already in super-protective mode. Didn't stop the worsenings though
It really goes to show how ridiculous it is that we normalize losing these upper bands, though.I got tinnitus at 18, so at a time when people were starting to party and club I was already in super-protective mode. Didn't stop the worsenings though
This was in a Petri dish, where they were trying to get clonal expansion to study the regeneration. If you read the whole thing, you will see they removed cells from a mouse cochlea and put it in a Petri dish. In vivo there are limits to clonal expansion and that's good, otherwise this drug would cause cancer.
Thinking about the fact that their Cell paper was in 2017 and they have gone from Petri dish to human trials since, puts it in perspective for me. They are definitely interested in getting this to people as soon as possible.
Most ENT doctors do not treat tinnitus because this is not their area of expertise. They are physicians not tinnitus specialists. They treat underlying medical conditions within the auditory system and ear nose and throat that causes the tinnitus. They treat these conditions medically or surgically. Those that have knowledge of tinnitus is as you've found to be quite lacking. Some have more insight into tinnitus because they have it, but usually it's mild and nothing like you or other members in this forum experience.
When a patient's tinnitus is not caused by an underlying medical problem they should be referred from ENT to Audiology for treatment as is the current practice in the UK. Here, they will usually see an Audiologist sometimes a Hearing Therapist. The role of the Audiologist is to fit a patient with hearing aids, white noise generators and carry out hearing tests. They can also diagnose other problems affecting the ears and fit patients with cochlear implants and help with speech therapy. Some branch out and specialise in tinnitus and hyperacusis management and treatment. This can be particularly helpful when counselling is required which is often used in TRT and CBT. Usually these Audiologists will have tinnitus. They were either born with it or acquired it at some time in their life. Some also counsel people with phonophobia and misophonia. Both these conditions can affect a person that has tinnitus and hyperacusis.
The role of the Hearing Therapist is similar to an Audiologist. They counsel patients with hearing loss, tinnitus, hyperacusis and other problems affecting the auditory system. Many have tinnitus as does my hearing therapist who was born with it. I believe for an Audiologist or Hearing Therapist to give good quality counselling to a tinnitus patient, they have got to have tinnitus. Unless they have tinnitus they cannot understand or know how the condition affects a person's mental and emotional wellbeing. Therefore, at best the counselling will be unconvincing and mediocre something the patient will quickly realize.
For this reason I have no interest in attending tinnitus seminars and conferences, for they are often hosted by ENT doctors and Audiologists who are medically qualified and know about the anatomy of the ear and problems associated with it, but most have no understanding of tinnitus or hyperacusis because they have never experienced them. Through consultation with patients they can learn how these conditions can affect a person but their depth of knowledge and understanding will often leave a lot to be desired.
Michael
Thuan
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- Jul 5, 2020
- 221
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- 05/2018
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- Ear infection right ear 2018. Sound trauma left ear 2020.
I agree but I think only people with moderate tinnitus or worse can truly understand sufferers who visit this forum. I have seen GPs, ENTs, and emergency docs (basically crying for help when my tinnitus spiked so loud). Of all these doctors, only one has very mild tinnitus and he brushes off my suffering. All the doctors I have seen do not even consider moderate and severe tinnitus as a debilitating symptom akin to severe pain.
It is their low opinions on tinnitus that stalls any progress in tinnitus research and treatment. Even doctors in Tinnitus Talk (I highly respect your opinions and care in this forum) do not advocate for finding an effective treatment or even a path towards a cure, which is very discouraging and pessimistic. These are very educated and capable professionals and yet.. they have given up and just live by the day.
Like I have said before, if no one capable cares enough to find a cure, then we will never get one. The only people doing tinnitus research are academic professors and PhD students, which mostly focuses on understanding tinnitus. The only entities that try to find an effective treatment and cure are profit companies, like Frequency Therapeutics and Otonomy (and to a certain extent Hough). Overall, there are very few efforts put into tinnitus.
I also agree about your opinions on the various tinnitus associations. I have gone to one meeting with the American Tinnitus Association hoping for some understanding but the entire meeting was about acceptance, habituation and an emphasis that there will be no cure. WHAT THE EFFING #$%*. It's as if the entire association itself has give up on treating tinnitus! Yeah, their websites has these "research" aspects but their real feelings are the opposite.
But companies like Frequency Therapeutics and Otonomy at least are striving for some effective treatment. I applaud their goals even if it's non-altruistic.
/end rant
This is the analogy I gave to someone recently:
Imagine there was a disease that caused itching. It could cause anywhere from mild to severe, intense untreatable, unrelenting itching/burning.
Now imagine if current treatments for the moderate to severe types involved machines that helped you disguise the itch with artificial scratching (helped you scratch more places I guess, it's an imperfect analogy but just go with it...), drugs to sedate you or decrease anxiety about your itching or counseling centered around coping and habituating to your itch problem.
Now imagine the people with milder itching telling the more severe itchers they don't understand why they can't live normal lives or people telling them to be as positive about their itch situation as possible (which the severe itcher would love to be able to do but all they think about it the non stop itching).
To the moderate to severe itcher, only one thing would make life better and that's less itching but at the specialists' meetings they tell all the doctors to tell the itchers to try psychological treatments (where they say things like "the itching won't kill you! Imagine it's just a million feathers on you).
Anyway, I'm glad there are researchers who finally want to address the underlying causes of hearing disorders because that's what will ultimate save the millions who suffer.
@Thuan
Due to lack of manners and respect by certain members of this forum, I no longer engage in correspondence with them and have had to place persistent troublemakers on ignore. Their only agenda is to cause disharmony and discord and that's not the reason I visit here. In my first post the quote I highlighted, was to explain to anyone reading it, that might have the opinion, many ENT doctors and Audiologists lack knowledge and understanding of tinnitus.
Your post was respectful and for this reason I am replying to you. I will correspond with any member that is respectful and not trying to play one-upmanship with me. You have made some crucial and very valid points that I agree with. Tinnitus has been around for centuries and goes back to the Egyptians when the first medical account and treatment for it was recorded. They applied infused oil, frankincense and tree sap to the external part of the ear using a reed stalk to help those suffering with the condition. Today there are many treatments for tinnitus to enable people to have a better quality of life, some I've mentioned in my previous post.
Like most people with tinnitus I welcome a cure but at present there isn't one, so we just have to get along with life doing the best we can. I read a newspaper article many years ago when I first got tinnitus mentioning: Nineteen out of twenty medical conditions cannot be cured but many can be treated, to help people have a better quality of life.
I wish you well,
Michael
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
It's embarrassing that some people can't process this. Imagine thinking "ringing in the ears is ringing in the ears," with how complicated the brain and inner ear are. And WORSE, these people have advanced training on these systems. How is it that a bunch of lay people on an internet forum understand the inner ear enough to see that these conditions can vary just based on really simple things like hidden hearing loss?
A funny thing about CBT is that your brain has to actually be capable of learning that sounds are okay. If sounds are not okay, it will only keep learning that they are not. You can't always just will your way.
I realize we repeat a lot of the same rants, but this cannot be forgotten. Researchers need to see the sheer number of people saying the same thing.
Thuan
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- Jul 5, 2020
- 221
- Tinnitus Since
- 05/2018
- Cause of Tinnitus
- Ear infection right ear 2018. Sound trauma left ear 2020.
From the Tinnitus Talk Podcast transcript:
Under section "44:56 Stimulating progenitor cells – does it work for all?":
"And as you say, there could be certain conditions where those are damaged. Or they are no longer intact...So, we think yes, there may be a small percentage of individuals, their progenitor cells are no longer functional or intact, they may not be candidates for FX-322, but we think, the vast majority would [have some intact support cells]."
Take it with a grain of salt since he's only basing it on a some donated cochlear organs and their audiograms. We all just have to see how their phase 2 performs.
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
"Some" donated cochleas were actually "hundreds" - Source from the JP Morgan recording in January.
Thuan
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- Jul 5, 2020
- 221
- Tinnitus Since
- 05/2018
- Cause of Tinnitus
- Ear infection right ear 2018. Sound trauma left ear 2020.
Nice! I hope then we'll all have enough support cells. Do you have a link to the JP Morgan source? Is there anything else interesting that they mention?
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
I wish I did! They keep past events on their website, but only for a certain timeframe. I believe it was Lucchino or Loose who mentioned sourcing hundreds of cochleas for testing/verification in the lab prior to filing the IND. It was in response to a question re: how they knew FX-322 actually grew hair cells.
It may have been highlighted here in this thread around that time. This thread is like a rolling history of developments as they occur... almost a second-hand source.
On a hypothetical basis, let's say Phase 2a results are announced during the spring of 2021. Let's also say the data shows that the drug is highly effective in meeting many primary and secondary outcome measures.
If the company's compassionate use/expanded access policy is revisited and granted as a result, how long does everyone think it will be until we can obtain access?
If the company's compassionate use/expanded access policy is revisited and granted as a result, how long does everyone think it will be until we can obtain access?
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
It will depend on how quickly the drug can be readily made available. I'd say 6 months to a year.
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