Hmm... Maybe.
Yeah, the brain isn't damaged due to noise-induced or sudden sensorineural hearing loss and therefore doesn't need restored.
A hum in a mixer/sound system can be caused by many things, but if it's caused by a faulty microphone cable, and you replace the cable, the hum won't be "stuck in the mixer", it will stop.
I like the analogies, but they are of course naive and inaccurate. The brain is arguebly one of the most complex things in the universe. The understanding of tinnitus is mostly based around theories, so only the future will tell what actually happens when you restore hearing.
You're right, the comparison is ridiculous, the brain is not a microphone. If it were that simple, Alzheimer's would have been cured for centuries.
Although it's a good analogy, you can't compare tinnitus to a microphone cable and a mixer, lol. That's far too simplistic and shortsighted. Are mixers capable of processing emotions, intellectual thought, or are they self-aware? Do they get depressed, anxious, or obsessed?
The problem with analogies is sometimes people draw the wrong conclusions. Anyone who's ever disconnected a guitar from the cable without turning the volume down on the amplifier first has heard that distinct buzzing sound. It could very well be that the nerves (cable) have been disconnected from the cochlear (guitar) therefore producing tinnitus due to the nerves propagating stray signals. A damaged guitar (cochlear) will also produce buzzing for the same underlying reason - lack of connection to, or damaged pickups (stereocilia). Until there is solid proof otherwise I believe this is plausible reasoning.
I'm not sure how emotions got mixed into this? A cochlea is typically damaged by noise, aging, infection, medication. This is reinforced in academics and commercially. Reversing the damage in this peripheral sensory organ is what FX-345 and many of the other locally administered drugs are designed to do.
Because our emotions directly affect so many biological processes in our body, from our endocrine system, brain chemistry, limbic system, etc. This all has an impact on how our brains react to various stimuli because our bodies are always attempting to return to a state of homeostasis.
I would argue that this is an extremely simplified reasoning that only looks at one subset of sufferers, and even then, it doesn't completely explain what is happening. There are too many unexplained variables and not enough evidence, either way, to make any meaningful conclusions (at this point). Let me be clear here, I'm not saying that by resolving hearing loss we couldn't expect to see tinnitus abate in various individuals. It absolutely could, and there are reasons to believe this would be the case. Would this work for everyone? I'd say not, and I'd go further and say that it would likely only work on a subset of those who have tinnitus caused by sensorineural hearing loss.
This does happen. High levels of cortisol that are sustained can wreak havoc on the body, and this includes the auditory system. It can affect blood flow into the inner ear by restricting the tiny capillaries, which in turn can restrict oxygen to the cells. It can affect glutamate transmission, and it can even shrink one's brain. Stress is often seen as a precursor to tinnitus; it's so common that it's become a highly studied area. Anecdotally, you hear so many stories about people experiencing the onset of their tinnitus during stressful events, such as during pregnancy, with burnout syndrome, depression, anxiety, etc. The idea that it's just because of a faulty cable, in all cases, seems highly suspect to me. That's just my opinion, though.
I have no problem with the idea that the brain is plastic enough to remodel itself and reverse the tinnitus based upon the root cause being fixed. I'm saying there are too many root causes and likely complex interactions within the brain that span beyond the initial cause in many individuals. We need to better understand the heterogeneity of this condition.
I'm not sure you understand what I meant and also what @dbeats says, but you address me anyway.
They won't. The first one won't be for another year, in late 2022. It will probably take almost another year to run the trial and release the results, sometime in late 2023.
And yet when we dream we don't have tinnitus. Even though our ears are still damaged when we are dreaming. I've always been fascinated by that. There exists some state in which altering the brain stops tinnitus.
Even for people with sensorineural hearing loss, the aetiology of their tinnitus is likely to be varied. The pathophysiological mechanisms are still not fully understood, but we know that it is a very heterogeneous condition, so it's a bit of a minefield. It's likely that fixing one's hearing loss will only work for a subset of people, and that's if it works at all. I think there's also an argument to be made about the period of time that one has had chronic tinnitus and what can be expected as an outcome.
This is something else that cannot be explained by hearing loss alone. Many people have tinnitus that fluctuates quite considerably based upon their emotional state, sleep hygiene, jaw tension, neck tension, etc. You also have to remember that hearing loss doesn't always lead to tinnitus, so the faulty cable to the mixer analogy is flawed in this regard as it's a bit too selective and convenient, in my opinion. What we have to ask ourselves is what's different about the brains where tinnitus emerges as a symptom and the ones where it doesn't.
You could be absolutely spot on with your assertion. All I'm saying is that there isn't much to go by in order to predict what would happen with any kind of certainty, and we haven't regenerated anyone's hearing yet, so our current knowledge base is limited.
Frequency Therapeutics cites the research/publications behind PCA (Progenitor Cell Activation) and FX-322 on their website:
That is, do I understand correctly that Frequency Therapeutics conducted the testing themselves, and summed up the results and results themselves? Do you trust this company? Why can we trust that their goals are honest? What is your position on this issue? It is very likely that their goal is to make money not so much by creating a medicine as by deceiving the trust of investors.
The early published work was conducted by the founders prior to forming the company, under a lab operated by the highly-respected Robert Langer (also, the founder of Moderna, and others). Langer is also a co-founder.That is, do I understand correctly that Frequency Therapeutics conducted the testing themselves, and summed up the results and results themselves? Do you trust this company? Why can we trust that their goals are honest? What is your position on this issue? It is very likely that their goal is to make money not so much by creating a medicine as by deceiving the trust of investors.
...and probably almost all people devolop (more or less serious) hearing loss during their life span (mostly, at older age, but with a generation growing up with AirPods in their ears more and more), but still the question is why in some people the neurons go bonkers and other just get worse hearing but no tinnitus. Not that I understand it, but comparing these group might be an interesting approach to understand tinnitus:
I personally suspect that genetics are what causes that discrepancy. Maybe some people's brains are "wired"/predisposed through genetics to develop tinnitus while others are not. I'll just say that my case is clearly noise induced, and tinnitus is present 3 generations back on my mother's side, while my father can seemingly hunt repeatedly without hearing protection and not get tinnitus. In my case, I've clearly inherited the predisposition to develop tinnitus.
Thank you very much for the detailed answer.
Very encouraging. 
To my knowledge, Frequency Therapeutics is the first clinical stage biotech company to activate progenitor cells in the body using small molecules. FX-322 is their first attempt at a drug that causes temporary progenitor activation.Thank you very much for the detailed answer.
It's great that Frequency Therapeutics does not give up and announces the development of a new generation drug FX-345. This cannot but rejoice us.
What are the medical achievements of Frequency Therapeutics? Didn't the second phase of trials of the previous generation drug FX-322 fail? FX-345 is its continuation and inherits the technology. Investors now want to file a class action lawsuit against the Frequency Therapeutics director.
Sincerely,
Artem
I am certainly not a bioengineer and very far from science. But why not use the subjects' audiogram as a control, if there really is an interest in the objectivity of the results?
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