Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus
- Thread starter attheedgeofscience
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Well, well, well. We are all suffering with Tinnitus, to my mind it does't matter what we do it's there and we don't want it. What we all want is silence, so we can get on with life as I guess we all did before we were burdened with this appaling affliction. If they find an effective cure in the next twelve months we will all be celebrating! But finding an effective cure has been going on for a very long time, so for one I'm not very oppimistic for an across the counter cure. Sorry if I sound negative but just being a realist.
MemberAgreed, but I think maybe stem cells research and the like might help in a longer perspective
I doubt in 20 years we will know as little as now. And Autifony might still turn out to treat the condition quite effectively giving people with loud tinnitus a better quality of life. But yes, I agree with the cautious optimsm point of view.
does anyone think that we are looking at a cure with autifony do u guys think that Aut00068 is a cure since it removed tinnitus from rats?
I highly doubt that AUT00063 will be a cure. A cure implies that if you take it for a certain amount of time, your tinnitus is gone. I would bet my next paycheck that if AUT00063 is approved, you will have to take it for the rest of your life, and it most likely will diminish or greatly diminish tinnitus, but not make it completely disappear. However, since we know that quieter tinnitus is almost always more easy to habituate to, this is a very acceptable result in and of itself. Cures in medicine are far and few between. What is much more common are successful treatments.
There's not enough data either way, but papers from Autifony's scientists have suggested that they hope the effect could be permanent. They are seeking to induce adaptations in the brain, and it is known that the brain sometimes perpetuates conditions that are forced on it from outside. This is what they mean by "neural plasticity".
The theory is that "permanent" tinnitus comes from bad plasticity - something bad happens that causes fleeting tinnitus and the brain for whatever reason adopts this as the normal state and perpetuates it. It's important to realize that the brain is doing this on a deep, subconscious level. It's not deciding it likes the crazy noises in your head, rather it's going, "Hmm, this chemical is at a higher dose than it should be. I better release some of that other chemical to level it out. Okay, that worked. I'll do that from now on." What AUT-00063 does (if it works) is force a change to that behavior. It forces your neurons to act differently, and the hope is that if they act differently for long enough, they'll keep acting differently when the drug is withdrawn.
But it is all theoretical. So far Mpt over on the retigabine thread was able to reduce his dosage of that drug from 900 to 800mg/day without recurrence of tinnitus. Since then he's been on vacation and hasn't posted on whether he was able to scale back further. He should be back sometime in the next ten days and hopefully will have good news about continued reductions.
For what it's worth, if AUT-00063 doesn't induce a permanent change but needs to be taken long-term, that's probably okay. It's highly unlikely to have the downsides of long-term retigabine or other such drugs.
The theory is that "permanent" tinnitus comes from bad plasticity - something bad happens that causes fleeting tinnitus and the brain for whatever reason adopts this as the normal state and perpetuates it. It's important to realize that the brain is doing this on a deep, subconscious level. It's not deciding it likes the crazy noises in your head, rather it's going, "Hmm, this chemical is at a higher dose than it should be. I better release some of that other chemical to level it out. Okay, that worked. I'll do that from now on." What AUT-00063 does (if it works) is force a change to that behavior. It forces your neurons to act differently, and the hope is that if they act differently for long enough, they'll keep acting differently when the drug is withdrawn.
But it is all theoretical. So far Mpt over on the retigabine thread was able to reduce his dosage of that drug from 900 to 800mg/day without recurrence of tinnitus. Since then he's been on vacation and hasn't posted on whether he was able to scale back further. He should be back sometime in the next ten days and hopefully will have good news about continued reductions.
For what it's worth, if AUT-00063 doesn't induce a permanent change but needs to be taken long-term, that's probably okay. It's highly unlikely to have the downsides of long-term retigabine or other such drugs.
I'd rather not but If it helps I'd take it everyday. .......of course need to know what the side effects are of course. If acceptable.....sign me up.
Everyone looks at a cure a different way.. A biological cure which will eventually happen.. Honestly maybe not for another 15-50 years but who knows i could be wrong cause im not a scientist or researcher.. But autifonys deff a start with a treatment cure if it works(fingers crossed) if we gotta take a pill for the rest of our life to control the noise then to me thats a cure. Is it gonna totally take the noise down? Idk maybe or maybe not. It may have mixed reviews like potiga did.. But maybe not since autifonys targetting the right channel thats invovled with T so theres a reason we should at least have some hope of it workin better then potiga. Its all a waiting game tho.. No matter what though theres people out there workin on figuring this shit out so whoever comes up with a stabilized efficiant treatment worldwide will be richhhh $$$$$$ but i have high hopes in autifony until proven otherwise
Hope is really all we have to keep us going....in many things in life. But from what I am reading and understanding autifony definitely seems to be on the right track. If this is a pill to take everyday like a blood pressure pill then I'm taking it......again let's pray there aren't serious side effects.Everyone looks at a cure a different way.. A biological cure which will eventually happen.. Honestly maybe not for another 15-50 years but who knows i could be wrong cause im not a scientist or researcher.. But autifonys deff a start with a treatment cure if it works(fingers crossed) if we gotta take a pill for the rest of our life to control the noise then to me thats a cure. Is it gonna totally take the noise down? Idk maybe or maybe not. It may have mixed reviews like potiga did.. But maybe not since autifonys targetting the right channel thats invovled with T so theres a reason we should at least have some hope of it workin better then potiga. Its all a waiting game tho.. No matter what though theres people out there workin on figuring this shit out so whoever comes up with a stabilized efficiant treatment worldwide will be richhhh $$$$$$ but i have high hopes in autifony until proven otherwise
And yes I'm sure autifony has their eyes on the billions the VA is spending annually on T disabilities and treatments.Everyone looks at a cure a different way.. A biological cure which will eventually happen.. Honestly maybe not for another 15-50 years but who knows i could be wrong cause im not a scientist or researcher.. But autifonys deff a start with a treatment cure if it works(fingers crossed) if we gotta take a pill for the rest of our life to control the noise then to me thats a cure. Is it gonna totally take the noise down? Idk maybe or maybe not. It may have mixed reviews like potiga did.. But maybe not since autifonys targetting the right channel thats invovled with T so theres a reason we should at least have some hope of it workin better then potiga. Its all a waiting game tho.. No matter what though theres people out there workin on figuring this shit out so whoever comes up with a stabilized efficiant treatment worldwide will be richhhh $$$$$$ but i have high hopes in autifony until proven otherwise
Exactly! My mind is thinking far away from a cure.. Cause like others said thats just like very few.. But like you said with blood pressure and diabetes or any other illness/symtom most can all be controlled and thats what we need a controlled substance to get this thing on a leash so we can control it!! And if we have to take a pill for the rest of our life to keep the noise down then so be it thats a cure too me until they biologically figure it out to prevent/or cure it without having to take anything. Everything is pharmaseuticals these days with any condition so autifonys drug could be the FIRST to control tinnitus. Fingers crossed!!!
I believe that it will vary person to person, perhaps there will be people that meets permanent relief, while others feel temporary relief of their condition so they will have to stay on it for a long time, and for some this drug will have no positive effects. I also believe that the degree of effectiveness will also vary individually, some people will have complete cessation of T sounds, while others will have moderate to high decrease in T volume. This seems to be the case with many psychoactive substances, everyone is wired differently and the complexity of psychoactive substances are huge, especially between individuals, see Retigabine thread for instance - AUT00063 will have less side effects I'm assuming, but the degree of effectiveness will widely vary. However, I am almost positive that drugs like AUT00063 will open the door to vast varieties of drugs that can help cure/treat tinnitus psychoactively, soon there will be dozens of different psychoactive substances working through different mechanisms which one can try for their tinnitus.
Pessimism is unscientific. If the hypothesis about the creation of tinnitus by inactivation of voltage gated potassium channels is correct, then it follows that activation of those channels with eliminate tinnitus. If the further hypothesis that potassium channel inactivation is a learned response due to neural plasticity, it follows that countering this inactivation will lead to opposite plastic adaptations.
I think the only complication will be for people who have a persistent condition that perpetuates the tinnitus besides plasticity, which is why I'm looking to get my TMJ checked by a really good dentist.
I think the only complication will be for people who have a persistent condition that perpetuates the tinnitus besides plasticity, which is why I'm looking to get my TMJ checked by a really good dentist.
SoulStation
Member
Yea... Like am102... Which could also be a potassium channel modulator. I am on Retigabine and although it doesn't give me full cessation, it works. I am as sure about that as someone can be after being on a med for a month
That makes me happy cause you have chronic T and it has an impact on you.. So with autifony you could bennefit even greater.
This is a very hopeful sign that you as an individual reacts very well to potassium channel modulators for your tinnitus. Hopefully all of us can get the same positive reaction, but the realist in me knows that's probably not likely. There will be an unfortunate number of us that will just have to pass on Retigabine and AUT00063 due to no effects, or bad side effects.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495050/figure/F1/ This isn't really tinnitus related, but as an example for psychoactive drug development, this is the progression of effective anti-depressants. One thing leads to another, and now there's a whole array of things for patients to try if one type doesn't bode well.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176700/figure/F1/ Another example using anti-anxiety medication progression and research.
My point is, we have yet to even enter the "Golden Age" of tinnitus research, but we're getting there, where this condition is becoming more researched and experimented. This is why I am excited about AUT00063 it's like the catalyst of tinnitus specific psychoactive medication. Following this drug there will be other more refined drugs based on the same mechanism, while also leading to other novel mechanisms which hasn't been discovered yet. This is generally the nature of psychoactive drug progression. This whole thing is also excluding advances regenerative medicine and whole other avenues, so there's a lot going for us.
Look At the End of the freaking day. They just need to hurry up. yes im happy with the little progress researchers are making, YAY WIPTY DOO, but I GOT A LIFE TO LIVE, and IM not tryna live most of my life with T. i mean how screwed would yall feel if you had to endure constant loud tinnitus all your life. only for a breakthrough to happen when your on your death bed.
I know Im not a doctor but i really feel that no one is really trying. Your not gonna tell me that if Obama or Bill gates had this that this wouldnt have been cured already. and if not cured controlled. we can treat headaches but not harmless tinnitus?
anyways back to the topic sorry for the rant,
BUT YOU GUYS DONT KNOW HOW BAD IM DEPENDING ON THIS AUT00063.
I really hope it works for my noise induced NON HEARING LOSS TINNITUS!!.
does it work as in Reducing T or work as in helps you not care about it and fall asleep.
Oh n see your from NY.............
C'mon Mr. Gustavo Fring, don't tell me you don't have 30 million buried in the desert somewhere
Hudson, read Benryu's posts on the long Retigabine thread re potassium channel modulators. Very cool stuff. He backs up that this would not be needed as long term medication to work, like benzos. Plus AUT00063 targets specific potassium channels to t. He also says that this drug could target many etiologies of t, both acute and chronic, and gives evidence to back up these theories.
This was posted in another thread but fits better here:
http://journals.lww.com/thehearingj...g_Pours_in_for_Investigational_Hearing.1.aspx
http://journals.lww.com/thehearingj...g_Pours_in_for_Investigational_Hearing.1.aspx
SteveToHeal
Member
Interesting...."This first-in-class Kv3 potassium channel modulator, in the form of a once-per-day oral tablet, is also in development for the treatment of age-related hearing loss."
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Sorry, kinda late to the game here as have been too wrapped up in Retigabine to do much else. However, seeing as this thread is about Autifony, etc. and the Phase II trial criteria is/was a hot button issue...am I just "isolated" in regard to T and hearing loss frequency ranges???
I have talked to a lot of people with tinnitus over my lifetime (including my dad and brother), and it has always appeared to me that the vast majority of us (me included) have a high pitched version of "ringing", somewhere up in the 6,000 Hz and above range. The hearing loss tracks that in same zones...as expected.
So Autifony's hearing loss frequencies requirements strike me as being somewhat bizarre, to say the least.
I guess my question is...Is low frequency hearing loss (and T presumably) a helluva lot more common than I realized???
Presumably though, if AUT00063 works, and the Kv channels hypothesis pans out, it will not really matter what the frequency is.
Oh, and I am definitely more in the "kick down the doors" camp of the "K gates" with shock and awe doses, v. the slow build-up. The 800 mg once a day smacko dose in Autifony's Phase II description kinda gives that a bit more traction IMHO. Pity we can't do it with Retigabine right off as it is too risky. A blunt instrument v. the precision of AUT00063! (Let alone Retig. is not even targeting Kv3 channels).
Sigh...It could be along wait to try this stuff. *[No need to speculate about timing, but for sure I would prefer to be trailing AUT00063 right now than Retigabine!].
best, Zimichael
I have talked to a lot of people with tinnitus over my lifetime (including my dad and brother), and it has always appeared to me that the vast majority of us (me included) have a high pitched version of "ringing", somewhere up in the 6,000 Hz and above range. The hearing loss tracks that in same zones...as expected.
So Autifony's hearing loss frequencies requirements strike me as being somewhat bizarre, to say the least.
I guess my question is...Is low frequency hearing loss (and T presumably) a helluva lot more common than I realized???
Presumably though, if AUT00063 works, and the Kv channels hypothesis pans out, it will not really matter what the frequency is.
Oh, and I am definitely more in the "kick down the doors" camp of the "K gates" with shock and awe doses, v. the slow build-up. The 800 mg once a day smacko dose in Autifony's Phase II description kinda gives that a bit more traction IMHO. Pity we can't do it with Retigabine right off as it is too risky. A blunt instrument v. the precision of AUT00063! (Let alone Retig. is not even targeting Kv3 channels).
Sigh...It could be along wait to try this stuff. *[No need to speculate about timing, but for sure I would prefer to be trailing AUT00063 right now than Retigabine!].
best, Zimichael
SoulStation
Member
It's all your perception at the end of the day. But yes it has helped reduce the sounds. But I'm on a really low dose so it only works at a low level when it's in my blood stream....for me now though it has provided some very good moments for me in the last few weeks. I feel like it may be losing it's potency but Im also being hyper critical and vigilant these days.does it work as in Reducing T or work as in helps you not care about it and fall asleep.
SoulStation
Member
@Zimichael, from everything I've read, high pitched tinnitus is the norm. I am an exception, with a droning hum just a bit above 1000Hz.
However, the reason Autifony picked that range was information from their "expert advisors", who are probably ENTs and audiologists. Audiologists check that range (and typically only that range) for two reasons. First, most voices fall into the range. Second, even the most sophisticated hearing aids are absolutely limited to amplifying sounds up to 10,000Hz. An aid must have twice the bandwidth it can usefully play for sampling purposes, and 20,000Hz is the most any behind-the-ear device is capable of sampling, due (IIRC) to the output of the battery. In fact I don't think any 10,000Hz aids actually exist outside experimental labs.
Audiologists test for hearing aids, and Autifony is being advised, most likely, by audiologists. It's worth noting that none of the management team at Autifony are hearing specialists. Dr Large is a molecular biologist and neuroscientist who studied Retigabine among other drugs, Dr Alvaro is a neuro chemist, and Dr Harris, who answered my emails, is an oncologist and nephrologist. They are all incredibly well qualified R&D experts, but the particular line of research they are on seems to have come out of the blue.
That might seem discouraging at first glance, but it is actually one of the reasons I'm most optimistic about AUT-00063. The only narrative I can imagine leading to Autifony's formation is the semi-accidental discovery that potassium channel modulation can be used as an effective treatment for tinnitus. Dr Large was in the perfect position to make such an observation, and was writing about Retigabine at around the same time U. of Pittsburgh docs were testing it as a protective drug against noise exposure.
I think they already know AUT-00063 works on tinnitus and they are doing the clinical trials half to prove it and half to test if the drug is also effective for hearing loss. I don't think they expect any trouble getting it to market as a tinnitus treatment, maybe cure, and are emphasizing the hearing loss requirement in the hopes that it can do even more.
However, the reason Autifony picked that range was information from their "expert advisors", who are probably ENTs and audiologists. Audiologists check that range (and typically only that range) for two reasons. First, most voices fall into the range. Second, even the most sophisticated hearing aids are absolutely limited to amplifying sounds up to 10,000Hz. An aid must have twice the bandwidth it can usefully play for sampling purposes, and 20,000Hz is the most any behind-the-ear device is capable of sampling, due (IIRC) to the output of the battery. In fact I don't think any 10,000Hz aids actually exist outside experimental labs.
Audiologists test for hearing aids, and Autifony is being advised, most likely, by audiologists. It's worth noting that none of the management team at Autifony are hearing specialists. Dr Large is a molecular biologist and neuroscientist who studied Retigabine among other drugs, Dr Alvaro is a neuro chemist, and Dr Harris, who answered my emails, is an oncologist and nephrologist. They are all incredibly well qualified R&D experts, but the particular line of research they are on seems to have come out of the blue.
That might seem discouraging at first glance, but it is actually one of the reasons I'm most optimistic about AUT-00063. The only narrative I can imagine leading to Autifony's formation is the semi-accidental discovery that potassium channel modulation can be used as an effective treatment for tinnitus. Dr Large was in the perfect position to make such an observation, and was writing about Retigabine at around the same time U. of Pittsburgh docs were testing it as a protective drug against noise exposure.
I think they already know AUT-00063 works on tinnitus and they are doing the clinical trials half to prove it and half to test if the drug is also effective for hearing loss. I don't think they expect any trouble getting it to market as a tinnitus treatment, maybe cure, and are emphasizing the hearing loss requirement in the hopes that it can do even more.
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