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Fully agree on that. Expected more discussion after I dropped the transcription on here.

Just look at the mess damage creates: Even the “healthy” hair cells are no longer properly aligned.

Isn’t the deal with Astellas for FX-322 alone?

I hear what you’re saying and both of you could be right, but at the moment I don’t want to draw any speculative conclusions beyond the actual facts. This might create high expectations amongst some people here who don’t look at the actual statement done by Chris Loose. Some people could be...

I cannot tell with absolute certainty from that text if the epithelial scarring would affect hair cell regeneration, but the text confirms my earlier statement that supporting cells move in place where the hair cell is lost. Looking at the images of noise induced damage for example does reveal...

Transcription: https://www.tinnitustalk.com/threads/frequency-therapeutics-—-hearing-loss-regeneration.18889/page-216 Audience: Besides the word score in phase 1/2, did you look at any other secondary end-points that would give you any indication of <inaudible>? Christopher Robert Loose (Chief...

In regards to epithelial scarring: Cochlear pathology, sensory cell death and regeneration https://academic.oup.com/bmb/article/63/1/25/377504 Contains a section on: Cell elimination and scar formation “... The term ‘scar’ is used to describe replacement of the original cell type (hair cell)...

@FGG should send her personal letter as she pleases. Entirely her effort and her decision. Tinnitus Hub and the community can send an additional separate and more formal letter. Though it’s probably best to wait for promising results in regards to tinnitus (e.g. after FX-322 phase 2a) as this...

Hi @Jorge P. Simoes, It is really great that researchers are reaching out to the biggest tinnitus patient community. Thank you so much for doing so. It is truly the right mindset to understand the need to engage with patients who actually have the condition. This is really positive. I very much...

As far as I know when a hair cell is removed from the epithelium, a supporting cell will move into that position to ensure structural integrity of the epithelium.

Completely different. People need to keep in mind that FX-322 only regenerates hair cells. So it can only resolve tinnitus for people whose tinnitus is the direct result of hair cell loss. If tinnitus is the result of cochlear synaptopathy you will need a solution like PIPE-505 or OTO-403...

I remember vaguely this has been discussed long ago, but I don’t know anything about this. What exactly leads to epithelial scarring? Why did @FGG and/or others not consider this a problem?

I don’t think lack of supporting cells is going to be a problem for the majority of us. I wouldn’t even disregard Audion’s solution because they don’t duplicate supporting cells. If Audion goes to market sooner they are certainly a worthy option to consider. I’m surprised to learn though that...

As far as I know it was never confirmed that his tinnitus and hyperacusis improved.

Do you have some good sources on this?

It seems odd to me that companies can buy the rights to a cellular pathway. So this means that other biochemical companies can not use that pathway, even if they could have or work out a better solution? Am I understanding that correctly? I already had this thought with Frequency Therapeutics...

It’s because the whole concept was born out of looking at regeneration in animals and the gastrointestinal system in humans. They discovered progenitor cells that regenerate the entire intestine every 2 weeks or so. When studying the body they found very similar progenitor cells in the cochlea...

Hi @brownbear, Nice to have an ENT with chronic tinnitus on Tinnitus Talk. It’s very nice to see you trying to help some people out by answering their questions, while you are clearly also impacted by your tinnitus severity. I was wondering if you are following up on hearing regeneration...

Very interesting publication on ototoxic damage to the inner ear which touches on intercellular connectivity, communication, collaboration, dependency, et cetera. Several worrying statements though like SGNs depending on neurotrophic factors of supporting cells to survive and so on. Good find...

Tinnitus has been described as a thalamocortical dysrhythmia of the auditory pathway. Visual Snow Syndrome has been described as a thalamocortical dysrhythmia of the visual pathway, but this syndrome usually includes tinnitus as well for most people with VSS, so in reality it’s a...

“No matter which part of the cochlea is addressed by an investigational drug: Outer hair cells, inner hair cells, cochlear synapse etc (I would be happy to discuss with you the drugs I am most optimistic about if you would like). I ask that, if any of these medications show efficacy in an...

Did Dr. De Ridder tell you that you have thalamocortical dysrhythmia?

Just want to add that it also included functional connectivity results (brain regions that communicate which each other). It’s the test which shows red lines for communicating regions. The report also contained signal generation by several brain regions (don’t recall what it is called) and this...

I expect them to be competitive enough to want the jackpot and the hiring information you posted proves that they are looking for a better “carrier/transporter” for their small molecules that can actually reach all the way down to the apex. It’s a matter of time.

I just went to Brai3n (Dr. De Ridder) and they did a Loretta qEEG test (with eyes closed and ear protection). Afterwards they showed me the results and it contained a brain image with 1) hyperactive auditory cortices and 2) another zone that was underactive. It also confirmed brain wave...

Just confirming that my Loretta qEEG indeed also demonstrated hyperactivity in my auditory cortices. It’s a strong indicator of tinnitus. Researchers say that we need objective biomarkers, but there must be something that can already be used today to demonstrate efficacy during clinical trials...

FX-322 will improve your hearing. Both IHC and OHC will be regenerated at the cochlear base. We already have proof that it works. I suspect there will already be a significant improvement for you. Hopefully that improvement can give you the energy to hold on for the other or improved solutions...

About the study, I see, that is a very important viewpoint and not something I’ve heard before and clearly misunderstood that this was the intention of the study. Let’s hope this becomes more common. As you say it’s usually the other way around. So that is a good point indeed. About the data...

It seems that many people think it will. If tinnitus is generated as a consequence of cochlear damage leading to maladaptive neuroplasticity, then it will likely reverse the maladaptive neuroplasticity as soon as the missing frequencies are present again. If this hypothesis is correct of course.

I have read your thread to have a better understanding of your hearing loss symptoms (how exactly music is distorted for you). My knowledge is not advanced enough to give you any decent or reliable input on your specific (complex) case, other than you certainly have a mix of issues going on. I...

My country has euthanasia laws. It’s not easy though to be approved for the procedure. Your family needs to support your request as well iirc. It’s not just up to you and you need to undergo an extensive evaluation by several doctors and psychiatrists. The most difficult part is convincing them...

@Hazel and @Markku, Tinnitus Talk provides better content than the American Tinnitus Association and British Tinnitus Association combined! Wonderful work and highly appreciated. Thanks to @Justin De Moss and Dr Kopke (HEI) for agreeing with the interview. Hope to see good results in the future!

It was a very difficult choice between 13 and 14. Research #13 is definitely a great choice as well.

I think the triggers are reasonably well known. Question is what the exact physical damage is (in the ear or even the brain) that creates tinnitus. That is still not clear today as far as I know. I have read that some people speculate that some people with tinnitus are picking up somatic brain...

That would actually be great news. Do you remember where they stated this?

Absolutely, but these would be the main individual components. Anyone surely has a combination of different scenarios. It is even possible that it is due to the mix of different issues that the brain reacts erroneously.

It’s just speculation on my part. I cannot imagine this having no effect. I suspect it would be most noticeable when your hearing is challenged and this will happen more likely with music as it’s a complex mix of different frequencies and loudness and requires your hearing to work harder. So...

Research needs to focus on hard science. Tinnitus researchers need to do deep physiological, biological, otological and neurological research and so on, but this obviously depends heavily on research into technological advancements as well (imaging techniques for example). These fields need to...

I still need to have a deeper look at the current theories for tinnitus and hyperacusis and how exactly it relates to cochlear physiology and beyond. I have hyperacusis too, but it’s not my primary concern. I suspect it would still be scenario 1-7 that is primarily involved in the pathogenesis...

Small adjustment: Most common cochlear damage I suspect is: 1. OHC synapse reduction (synaptopathy) 2. IHC synapse reduction (synaptopathy) 3. OHC stereocilia damage 4. IHC stereocilia damage 5. OHC death (apoptosis) 6. IHC death (apoptosis) 7. Auditory nerve damage 8. Supporting cells 9. Stria...

No sources for the impact of stria vascularis damage on hearing, pure speculation on my part based on my current understanding of cochlear physiology. I just want to point out that most people likely think that sound waves make the stereocilia vibrate and this produces a signal towards the...

I see dynamic dots all the time across my entire field of vision. The dynamic of the visual snow creates a heat wave like vision. It’s very visible even during the day, but in the dark it seems even more intense. Unfortunately I see a lot more than just visual snow and it all compounds on each...

I can only speculate on what the exact impact is of damage to the stria vascularis. I know it is an essential supporting function required to make hair cells function. Hair cells can be perfectly intact, but will do nothing if the stria vascularis doesn’t work. They will simply not generate the...

I believe tinnitus can arise anywhere along the auditory pathway where there is abnormal neuronal activity that is interpreted by the brain as an auditory signal. Best example is neck injuries causing tinnitus. It’s because of physical pressure on the intermediary nuclei in the auditory pathway...

I wish there was something I could do for you. I think I understand the pain well of losing so much. I’ve basically lost everything I worked for my entire life. Past few days I’ve been going through so many emotions, I thought I would finally break down and end it. I still cannot accept that I...

If the tinnitus is generated due to basic cochlear damage resulting in some form of maladaptive neuroplasticity, then it’s very plausible in my opinion that this neuroplasticity will be reversed when the damaged frequencies are restored. Nobody is sure however until we get there. If there is no...

Sorry to hear this. Really would have been awesome to have an insider. I’m disappointed you tried so hard on the word recognition test. :p All you had to do was miss at least 15% of the words to get the magic candy. How hard can that be? :D Doesn’t make much sense though that you had 100%, but...

You’re absolutely right and even then it is still an inadequate test. In my opinion all hearing tests are archaic and insufficient. By the time something shows up on an audiogram there is probably already extensive damage. It’s kinda sad to see people say they have perfect hearing, because their...

IHCs (about 3500) are the primary hair cells responsible for transmitting the auditory signal to the brain. They are mainly afferent and take up to 90/95% of the spiral ganglion cells in the auditory nerve. Sound is primarily transmitted to the brain by IHCs, not by OHCs. OHCs (about 12000) on...

People with noised induced damage likely have less cochlear damage; primarily IHC, OHC and synapses. IHCs and OHCs may be damaged or may have died. IHCs and OHCs can still be present and function, but with decreased synapses. Loud sound waves probably only affect these structures directly. I...

Wouldn’t Frequency Therapeutics be capable of making a supporting cell “multiplicator” rather easily? If they can divide supporting cells into a supporting cell that transdifferentiates into a hair cell and leaves a copy behind, surely they’re capable of making a solution that just divides...

I don’t think damage to the stria vascularis will affect the efficacy of FX-322 in any way, but damage to the stria vascularis will continue to affect your hearing after hair cell regeneration and resynapsing though. I also don’t see a way though that this could create or contribute to...

I’ve done atlas reflex therapy and was told that my C1 and C2 were not well aligned. I’ve done two sessions where I was ‘cracked’ in several ways as well as in my back somewhere along my vertebrae. Aside from some temporary physical relief it did not affect my VSS symptoms in any way. I try to...

Why would the small molecules get deeper into the cochlea for IHCs than for OHCs? I don’t see why it would be any different for IHCs. They emphasise clarity in regards to the >8kHz region, because their solution is limited in the sense that it does not get beyond the base of the cochlea. In...

Awesome. Rooting for you. Do we agree on some secret language now or do we work that out later? Maybe post some rocking banana emoticons if your tinnitus improves? :rockingbanana: What category of hearing loss do you have?

I’m puzzled by this. Why do audiograms (and OAE tests as well in fact) only test OHCs? If that’s true then ENTs are even more full of **** than I already thought when they say that your hearing is fine after an audiogram.

ENTs knowledge is outdated. Extended audiograms must become standard. Ignore the ENT and go for it. Remember you may have lost lots of synapse ribbons per hair cell and that will not be clear from an audiogram, but will affect your hearing capabilities. You have not lost most of the UHF...

It’s sad to say this, but this condition has made me no longer fear death. Suffering is all that is left and the only thing I can do is to stretch the suffering as long as I can. It’s pointless and I only go on because I see the pain in my mother’s eyes when I try to express my true feelings...

In my opinion the current state of imaging technology is the main reason why we can’t figure out tinnitus, hyperacusis, visual snow and so many other neurological disorders and conditions. We are simply not capable of seeing what happens in the brain on the neuronal level. We just can’t see...