Episode 12: Hearing Lost and Found — Frequency Therapeutics

[serendipity1996]

The research is out there through PubMed and other medical research sources. I have neither the time, nor inclination, to chase it all down to present it. Feel free to accept it or not, but it's factual. It's only in the last several years as more data has been collated on the subject that the picture has become clearer that most people who suffer from tinnitus suffer from somatosensory tinnitus as related to the aforementioned issues - estimated now upward of 70% of all tinnitus sufferers.

And it doesn't matter if it's somatic tinnitus or not. Tinnitus is a neurological condition, period. It starts and stops because of confusion and resolution in the brain. It's not an ear condition.

Really? What about the research indicating that noise-induced tinnitus would be best alleviated by restoring hearing, as per the Hearing Health Foundation?

https://hearinghealthfoundation.org/blogs/tinnitus-and-noise-trauma-to-the-inner-ear

"Mounting evidence implicates tinnitus as an indicator of underlying auditory deficits, however mild these deficits might be, and including "hidden hearing loss" that isn't captured via the standard audiogram. This takes us from the former concept of "some form of hearing loss is associated with tinnitus" to a picture in which "tinnitus is a symptom of a form of hearing loss."

An early theory considers tinnitus to be a result of nerve hyperactivity that is overcompensating for the lack of neural input from the ear to the brain that would be occurring with a healthy inner ear. Even normal hearing volunteers who wore silicone earplugs for seven days to simulate a temporary hearing loss developed tinnitus in that short timescale, although the tinnitus resolved after removing the earplug.

In other words, a sudden reduction in cochlear output seems to cause increased spontaneous neural activity in reaction to the lack of signals. This leads to the perception of a continuous sound and may also underlie the hyperacusis, or a lowered threshold to discomfort from sound, often associated with chronic noise-induced tinnitus.

In conclusion, all indications are that tinnitus, when not caused directly by a central nervous system issue (e.g., stroke), is always associated with one or more forms of hearing loss. As a result, although a treatment of most forms of tinnitus will likely emerge in the years to come, curing tinnitus will first require curing hearing loss. It also points to tinnitus potentially being an early symptom of an underlying auditory injury before measurable audiometric changes."

 

[mrbrightside614]

It doesn't matter what the origin is. The condition itself is a neurological one, period. It's confusion in the brain that results in creating synaptic pathways that promote a self-reinforced negative feedback loop. The end result is the constant misfiring of the fusiform cells in the DCN. Most people that develop tinnitus already have a few other conditions that make them prime targets for. The final thing that actually sets it off is the straw that breaks the camel's back so to speak. And once it starts it's much more difficult to stop even if you resolve the physical issues that created it. That's because the condition represents a maladaptive plasticity in the brain. Most normal brains let those lost ranges go without a hitch - as they're supposed to. Ours don't. Lucky us.

This is why I have far more faith in neuromodulation devices to overcome this in the long run than chemical treatments. This is precisely what Susan Shore's work is about. Microshocks that interrupt the fusiform cells thereby resetting the DCN. That in turn should allow the brain the let those maladaptive pathways decay and there you have resolution of tinnitus regardless of its origin. Just like rebooting a PC.

Beyond the new neuroplasticity created by neuromodulation devices, they have a whole host of benefits, the most important being warding off memory loss and cognitive decline - actually reversing them in many cases.

I'm not interested in debating semantics here about the "true origin" of tinnitus because perhaps you're correct, but your order of events are off. Typically one has to have some kind of trauma to the ear to kickstart this cycle, so I would argue that it's still of physical origin.

Further, what can be inferred from your statement, you believe that your brain favors maladaptive plasticity, even in the event where the physical damage is corrected. This is both cynical and misleading, since the only information we have on this subject indicates that cochlear implants and regenerative technology has a positive impact on tinnitus.

 

[Tanni]

Typically one has to have some kind of trauma to the ear to kickstart this cycle, so I would argue that it's still of physical origin.

I don't know the answer either way -- (could you both be right, maybe?) -- but I also thought tinnitus was a neurological issue, ie in the brain, rather than in the ear, and therefore can be caused by both damage to the ear and damage to the brain. What about tinnitus caused by stress, for instance?

 

[Tanni]

I don't know the answer either way -- (could you both be right, maybe?) -- but I also thought tinnitus was a neurological issue, ie in the brain, rather than in the ear, and therefore can be caused by both damage to the ear and damage to the brain. What about tinnitus caused by stress, for instance?

I suppose this means that I don't think hearing regeneration will cure Tinnitus for everyone, as I think different origins need different cures, but this is just a layperson opinion. I know a lot less than most on here, who actually understand the science behind it.

 

[Keith Handy]

A wave of relief came over me when I heard that. The fact that patients told their ENTs - seemingly unprompted - that the drug improved their tinnitus is huge. I understand Carl pivoting away from this since it's unquantifiable at the moment, but this is a revelation. It's made me really excited about the coming Phase 2a results.

Imagine if someone from the Phase 2a studies came on this forum and said that FX-322 had improved their tinnitus, we'd all be going nuts. What Carl just said is that multiple people have experienced this. Now the big questions are how big an improvement they had and will we see the same thing in Phase 2a.

I'm wondering if this teaser of hopeful information (that we're all clinging to)—"some of them have offered that they have had improvements in tinnitus"—was publicly stated/known in some form at the time the interview was conducted and/or arranged?

Obviously, LeBel willingly did an interview for a tinnitus podcast; that in itself hints at a sliver of optimism. Is the context of the interview Frequency Therapeutics' first public mention of it, or were the anecdotes found buried deep in the research results somewhere, or previously mentioned elsewhere? Or was the pre-interview enthusiasm based only the fact that Frequency Therapeutics were adding tinnitus assessments to an upcoming (at the time) phase?

@mrbrightside614 @FGG @Hazel @Markku

 

[FGG]

I'm wondering if this teaser of hopeful information (that we're all clinging to)—"some of them have offered that they have had improvements in tinnitus"—was publicly stated/known in some form at the time the interview was conducted and/or arranged?

Obviously, LeBel willingly did an interview for a tinnitus podcast; that in itself hints at a sliver of optimism. Is the context of the interview Frequency Therapeutics' first public mention of it, or were the anecdotes found buried deep in the research results somewhere, or previously mentioned elsewhere? Or was the pre-interview enthusiasm based only the fact that Frequency Therapeutics were adding tinnitus assessments to an upcoming (at the time) phase?

@mrbrightside614 @FGG @Hazel @Markku

I can maybe answer this. @mrbrightside614 and I poured through all the known info and interviews we could find in preparation for this and couldn't find anything mentioned about tinnitus.

We submitted our questions in advance but were talking about how they would probably avoid the question since there was no data (at least publicly). I remember looking at him the night before and saying "if they dodge, ask them about anecdotes. Make them answer this!" And @mrbrightside614 was able to do it perfectly because he's awesome like that (and awesome in general, he's become almost a brother to me since the Tinnitus Talk Podcast).

 

[Keith Handy]

We submitted our questions in advance but were talking about how they would probably avoid the question since there was no data (at least publicly). I remember looking at him the night before and saying "if they dodge, ask them about anecdotes. Make them answer this!" And @mrbrightside614 was able to do it perfectly because he's awesome like that (and awesome in general, he's become almost a brother to me since the Tinnitus Talk Podcast).

That is so cool. "Make them answer this!" - I love it.

 

[Paulmanlike]

Anybody know or have a link to the presentation made today?

 

[ajc]

Anybody know or have a link to the presentation made today?

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