Does anyone know if cochlear implants can help tinnitus? Also how would you compare them to normal hearing? How long would you guys wait before getting cochlear implants?
Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
- Start date
How likely is it that FX-322 is going to do something for mild ultra high-frequency hearing loss (I mean the roll-off being at around 16-17 kHz)?
Is it possible that someone on the edge of normal hearing can take FX-322 treatment and restore their hearing to the perfect state of a newborn?
Or is FX-322 rather meant for severe hearing loss cases?
I feel really sorry to ask it here, please report if it breaks any rules.
Is it possible that someone on the edge of normal hearing can take FX-322 treatment and restore their hearing to the perfect state of a newborn?
Or is FX-322 rather meant for severe hearing loss cases?
I feel really sorry to ask it here, please report if it breaks any rules.
Member@RB2014 Sorry to hear about your situation, it really shows how different our genetics and how different our individual make-ups are.
I'm only a couple of years behind you age wise, but my teens and music life sounds the same as yours. Teens I spent going to gigs / concerts with bass heavy music (in fact it went well beyond my teens) and never had a big car system (until now).
Here's my audiogram to contrast with yours. I've had four done over the last 3 years all showing the same thing. I'm the total opposite from deaf, I can hear things other people can't and bird song can be so painful some days, even inside with all doors and windows shut I can still hear it, and more importantly I feel it triggering my hyperacusis.
FX-322 should deal with cases like the one you mentioned. In fact we don't know yet how well FX-322 will work although we do know it will work.
It is definitely designed to deal with very high frequency cases and will theoretically work with more significant cases as well.
The simple story is nobody knows at this time how well it will work with limited information around dosing outcomes, considering we only saw some limited testing outcomes in the initial trial.
All we know with certainty is that FX-322 works and that we have seen everything from improvement in the first trial to complete regrowth in a lab rat. Therefore how well FX-322 will work will be answered definitively in the clinical trials, though there might be some playing around with dosing to actually get it working the best.
If you look at the audiogram, the brackets indicate the hearing threshold when bone conducting devices were used vs "air" (standard headphones).
This indicates there is some component of loss due to sound not traveling into the cochlea correctly (i.e. ossicle or other middle ear disease, sometimes hydrops can cause a conductive loss too due to the stapes not functioning correctly in a hydropic ear).
In both those audiograms, if you took out the conductive component they'd be in the severe rather than profound range which is more what Frequency Therapeutics is testing for.
Cochlear implants do help most people greatly with tinnitus:
Can Cochlear Implants be a Tinnitus Cure?
As long as your tinnitus is in the range the cochlear implant covers (i.e. they don't put electrodes over 12000 Hz), they should make a difference.
Current cochlear implant hearing is usable but crude. It's generally good for speech but has problems with music and background noise.
They are working on an optical light based (vs. electrodes which are only as good as the amount of electrodes you can implant) cochlear implants. These will span the cochlea and provide much more natural hearing, however optic genes need to be inserted to read these signals.
It's really an interesting, multi disciplinary approach:
Towards the optical cochlear implant: optogenetic approaches for hearing restoration
Unfortunately, that also means they are a few years away.
How long you would wait depends on the individual. Maybe start a thread discussing this with other cochlear implant candidates.
I'm sorry about your hearing loss. Ototoxic medication is life destroying.
With what we know right now, I'd say you have a good shot at not only benefitting from FX-322 but also getting rid of tinnitus as a side bonus. My anxiety and fear gave me hyperacusis. A deaf person with hyperacusis... Crazy, right!!!! I could barely drive for a year because the low frequency road noise was unbearable. Once I got over it and just accepted where I'm at, the hyperacusis went away.
Thank you FGG for all of the information you provide to the thread! It is greatly appreciated!
The vast majority of your loss is SNHL but especially at 4000 Hz you have a significant air bone gap. If you read your audiologist's notes it even says "mainly SNHL."
Is this not yours?
Your audiologist described an air bone gap at 4000 Hz (they abbreviated it ABG) and described your audiogram as "mainly" SNHL.
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
@FGG I believe this quote from @RB2014 is crucial here. He states that 10 dB changes are easy to miss and he gets better at word scores the more they are read to him.
This was exactly what I was talking about in my earlier posts. This is what concerns me. This is why we cannot conclusively say that this works.
Not being negative as there are many reasons for excitement, I am both emotionally and financially invested in Frequency Therapeutics, but this is exactly what we need to consider and debate. It's a possibility despite Carl LeBel's quote of we can't strain our ears to hear more.
I'll also mention my hearing tests, where I have had differences of around 10 dB as well between tests that I think are attributed to my tinnitus levels at the time of testing.
I also wish I had thought about this to offer to Tinnitus Talk Podcast to ask Frequency Therapeutics about this in the interview, it does concern me.
@RB2014, my own audiologist said doubling word scores was unheard of. Do you feel like you could have doubled yours in a few months' period by them getting easier as @Paulmanlike is suggesting?
Basically the "air" part refers to the normal audiogram through a headphone. Do you remember them putting something next to your head at one point instead of playing sound through your ears?
That was the measure if you got a better audiogram directly through bone conduction vs passing through the middle ear.
If there is a difference it is known as an "air bone gap" and it's a sign of conductive hearing loss. That means your hearing loss is mixed (conductive and SNHL) but it is really only significant at 4000 Hz in your left ear and the vast majority of your hearing loss is SNHL.
It probably doesn't affect you too much but is a definite exclusion for FX-322 trials (it doesn't at all mean you couldn't benefit from the drug later though).
I really hope you're right man. This hearing loss is really taking a toll on me. I do not know how much longer I can do it. I don't have any kind of life anymore. I also just moved to the Keys so there isn't a lot of people here that have hearing loss. It's so hard to meet new people and make friends when you don't understand what's being said to you.
I am almost completely isolated, too. I can understand speech in person but have severe distortions that make life really hard to the point that I can't relate to people much anymore.
Hearing loss is absolutely devastating on its own but the loneliness just adds to it. ((Hug)).
Don't worry. Double blind placebo studies' very purpose is to eliminate this kind of problem.
Once again, of all the people who saw "statistically significant benefits", it was ONLY the people who received FX-322. Even the people with more minor benefits were given the drug. Placebo group remained essentially unchanged.
Plus the 21 month follow up basically showed that very little changed after almost 2 years. This only further rules out your fear.
Can you get better at speech or even an audiogram after some practice? Sure, but for that to be the reason why FX-322 saw success would be the GREATEST consistent coincidence in medical research history.
This isn't something that is up for debate. It's grade 9 science intro into testing. Don't worry and be happy and confident that FX-322 fixed hearing to a certain extent. Maybe that's the pinnacle of its power but unlikely... it's even more unlikely that the Phase 1 results were simply placebo.
Was it the same person giving the test? I learn how people talk and I get better the more I talk with them. If it was the same person that administered the test then it is possible that the person had a better shot at getting the words the second time around. Also it is possible that the second time they got better in general at deciphering the words because they had done it once before. I'm assuming the person giving the test had their mouth covered both times as well... because I can read lips like nobody's business. It is possible... maybe not probable, but possible.
Yes, Paulmanlike. I had read your post and you brought up some good points. I agree with them. When you are down 50 dB, 70 dB, 110 dB, the difference between negative 100 dB and 90 dB isn't that much. Tinnitus makes it even harder because sometimes I can hear the beep over tinnitus and sometimes I can't. A good or bad tinnitus day could sway it even further. Did the person play the tone again and say did you hear that? I might get it if someone did that... Did the second test replicate the first, or did the person doing the second test have the data from the first test and use that as starting points... There are so many variables and 10 dB is just not enough and it can easily be a margin of error as you have stated.
I'm not saying either of these things happened, but yes it is a possibility. Maybe the person gained 5 dB, not 10 dB... Maybe it was a combination of the person getting better and a very very small gain in frequencies above 8 kHz... Maybe some people that didn't show improvement in the audiogram actually gained 10 dB. Again many of us were hoping for better results. They should have already had an idea of what the proper dosing was for the trials.
I personally think FX-322 worked and the data somewhat supports that. These are however, valid concerns. Some people didn't improve on their audiograms... How well it worked and can additional doses replicate the results is to me the next question. If we end up with 5 dB to 10 dB at 8 kHz being the extent of the gains, I don't think it gets approved.
I've been dealing with this for a long time now. I keep going. Agreed, it's hard. I keep to myself a lot and I'm not as social as I was before. I let people know about my condition and it helps a bit. Learn to read lips... You probably never needed to do that before, but it helps a lot. Your accuracy will improve quite a bit. Stay away from noisy places if possible... that makes it more difficult if not impossible to hear what people are saying. Keep busy. Don't have anxiety over this, or your tinnitus just gets worse.
If multiple injections are effective in larger, somewhat deeper areas, I suspect they have the following advantages over single injections:
1) The appropriate effect can be adjusted with each injection.
2) Multiple injections, or annual or biennial injections, will be of economic benefit to Frequency Therapeutics.
For example, the hepatitis C drug Harvoni has provided enormous financial benefits to Gilead Sciences, but the benefits have only lasted for a few years as many patients have been completely cured.
In addition, the rheumatism drug Humira will provide AbbVie with financial benefits until 2023, when the patent expires, as it requires continuous dosing.
Of course, gel improvements to FX-322 will be made to reach deeper into the ear and to have greater therapeutic effects.
I think the gel improvement will be a special card when drugs with similar effects come out and compete in the market, but Frequency Therapeutics will balance the increased effectiveness of the drug with its economic benefits.
1) The appropriate effect can be adjusted with each injection.
2) Multiple injections, or annual or biennial injections, will be of economic benefit to Frequency Therapeutics.
For example, the hepatitis C drug Harvoni has provided enormous financial benefits to Gilead Sciences, but the benefits have only lasted for a few years as many patients have been completely cured.
In addition, the rheumatism drug Humira will provide AbbVie with financial benefits until 2023, when the patent expires, as it requires continuous dosing.
Of course, gel improvements to FX-322 will be made to reach deeper into the ear and to have greater therapeutic effects.
I think the gel improvement will be a special card when drugs with similar effects come out and compete in the market, but Frequency Therapeutics will balance the increased effectiveness of the drug with its economic benefits.
Well said.
It is one thing to go to the same audiologist over time and improve "your skills" at word recognition scores and make light of 10 dB alterations and another to immerse yourself in a Frequency Therapeutics 21-month clinical trial. For the closest to true accuracy, I'd place my bet on the latter.
Thanks for sharing excellent information about the other drugs. I definitely think that the economic considerations will come into it when determining what happens with Frequency Therapeutics' FX-322 andI also think that the two points that you have put forward are accurate.
Another thing that I would suggest is that there's probably no consideration given to redosing right now due to economic benefit. I think that there won't be any consideration into looking at redosing until they know that it is firstly a viable option and secondly that it is worth investing the money into. Therefore I don't think that there will be any investment into redosing by Frequency Therapeutics until they know that this is a wholly worthwhile investment that will pay dividends if they spend the money on it.
You'd hope it wasn't and you'd hope that the lists were randomised and given in a very controlled and standardised way. My memory of the graphs is that there was a small training effect for the placebo group. But that's why you have a control group. The effects you're speculating about would apply equally to both groups. You let the maths sort out the differences between the groups which should be due to whatever you're doing differently to the experimental group.
If the tests weren't applied carefully and systematically, you'd see a lot more variability which would make it less likely that you'd see a statistically significant effect.
Unlike @FGG's audiologist, the one I've run this by doesn't have much faith in word recognition scores. Thinks they're too variable and unreliable. If that's true though and they're still getting a statistically significant effect, that speaks for the magnitude of the effect they're getting.
Btw, if I were you I'd be cheering for gene therapy solutions more than FX-322. I note that the scientists who developed CRISP-R gene editing just got awarded a Nobel Prize. All the best.
Michael01
Member
I just received an e-mail stating when the results of the FX-322 trial will be released, if it's of any interest to anyone.
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
Word score tests are performed in the sound-proof booth. They're a randomized, 25 or 50 word set of pre-recorded prompts. They're played through headphones at roughly 50 dB. The patient is supposed to repeat what words they've heard.
Typically it's a voice saying, "Say the word 'crash'" for example.
There's no way to read lips, because there isn't a person telling you what to repeat. You're in the sound booth with no visual cues.
It's normal for patients to be +/- 3 words (a 6-word spread) if they retake the test on a regular basis. So, over the course of a year, you could have scores of 20, 23, 26, and 24, and that would be normal.
Patients that did not receive FX-322 in the Phase 1/2 stayed within this normal range across the 90-day testing window. Those with more to gain (the group of 5) saw their scores improve significantly higher than the normal 6-word variance.
Since the p-value on the word score chart in the frequency presentation is 0.010 for word score, we know that the others who received FX-322 also saw an improvement, although not statistically significant. Likely do to a ceiling effect.
My guess is that they saw 10-20% improvements on average in word score consistently within the +/- 3 range. This would help explain why the p-value is showing significance, and further reinforcing that it was FX-322 providing the benefit and nothing else.
For example: A mild patient may have been at 40 words at the start of the trial (+/- 3 giving them a range of 37-43 words). At the end of the trial they probably consistently scored 45 words (42-48 correct word range). These types of results will drive that p-value down, but not be very "groundbreaking" from a clinical or investor standpoint.
Typically it's a voice saying, "Say the word 'crash'" for example.
There's no way to read lips, because there isn't a person telling you what to repeat. You're in the sound booth with no visual cues.
It's normal for patients to be +/- 3 words (a 6-word spread) if they retake the test on a regular basis. So, over the course of a year, you could have scores of 20, 23, 26, and 24, and that would be normal.
Patients that did not receive FX-322 in the Phase 1/2 stayed within this normal range across the 90-day testing window. Those with more to gain (the group of 5) saw their scores improve significantly higher than the normal 6-word variance.
Since the p-value on the word score chart in the frequency presentation is 0.010 for word score, we know that the others who received FX-322 also saw an improvement, although not statistically significant. Likely do to a ceiling effect.
My guess is that they saw 10-20% improvements on average in word score consistently within the +/- 3 range. This would help explain why the p-value is showing significance, and further reinforcing that it was FX-322 providing the benefit and nothing else.
For example: A mild patient may have been at 40 words at the start of the trial (+/- 3 giving them a range of 37-43 words). At the end of the trial they probably consistently scored 45 words (42-48 correct word range). These types of results will drive that p-value down, but not be very "groundbreaking" from a clinical or investor standpoint.
Thank you for your evaluation.
That's right, I think Frequency Therapeutics wants to run straight to the market with its current specifications.
Therefore, I hope the Phase2a results are effective in the deeper low frequency range with multiple injections.
If this is demonstrated, I think it will have a great effect, for example, repeating a set of four injections at intervals of several months.
If the therapeutic effect reaches up to,it's the original goal,3500Hz
more patients will expect the effect, and more patients will need to inject that many times, so the unit price of the drug will be able to be set at a more accessible price.
They will be able to reduce the profit margin of the drug for a single injection.
I may be too optimistic.
Gene therapy solutions for hearing loss have, thus far, been formulated for genetic deafness. There is a place for it in those conditions which would not simply be a hair cell issue.
Novartis had an AAV therapy but there is a huge disadvantage with needing surgical insertion vs IT injection. It has potential, but there is so far a reason they only have tried this on very advanced cases (because if how destructive the particular surgery they used is).
I cheer on both personally because eventually companies hope to use genetic editing to transduce non hearing tissue (e.g.. fibroblast) in the very serious to profound cases where there could be notches of scaring but there are a lot of people that doesn't apply to and it seems a bit apples and orangey to compare the two.
I guess everyone does the tests differently.
My experience has been the opposite of what you mentioned. You are in a soundproof booth, sometimes they are there with you, sometimes they are on the other side of a clear glass. I've always been able to see the person administering the test while they are giving it and I have quite a few hearing tests under my belt...
I was following CRISPR for a while but from what I read you have to do it before you lose your hearing to rewrite the faulty gene that causes hearing loss. Once you've lost your hearing it is too late.
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