I didn't think of it that way. At the same time, I feel like all sorts of psychiatric medication is fast-tracked without too much intensive oversight and approved for use quickly, at least in the US. That's at least how it seems sometimes. And the people at autifony are essentially psychiatric pharmacologists by training. Who knows
Autifony Therapeutics Phase I Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus
- Thread starter Hudson
- Start date
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bill 112
Member
Yaaaaaaaaaaay!!!!!!!!!!!!!!Great news from Autifony yes I am most willing to participate but I first have to attend a neurologist as the UCL professor I am seeing is concerned about excess spinal fluid or something.Once that investigation is over he said he would happily help me sign up for this.Nice find Dan well done.
I could take philosophy in the UK so I can participate I suppose... Hmm
But I have a full time job now and finally getting my life back on track. Yesterday was 1 year anniversiry for my T. Im very happy these days. Dont feel the need to move in order to get a drug that will work in 7 years anyways.
Will see what I do!
But I have a full time job now and finally getting my life back on track. Yesterday was 1 year anniversiry for my T. Im very happy these days. Dont feel the need to move in order to get a drug that will work in 7 years anyways.
Will see what I do!
I think the efficacy is the 100% rat success rate. I don't think any other drug had such extreme rat model success. Can you find such results on say Neramexane? Otherwise, no I don't know what all the fuss is about really. Probably I'm over reacting. Just stupid rats I guess.
So should I be excited if phase 2 is successful, at what point do we get excited?
So should I be excited if phase 2 is successful, at what point do we get excited?
bill 112
Member
I think its ok to be excited as the drug that shows the most promise as a cure has been deemed safe for human use which a lot of new medication never does.If this drug had failed stage1 trials it would have been devastating and pretty much would have gone back to the drawing board for who knows how long.Everytime a drug like this passes they are a step closer to a cure and with a 100% success in the rat model its hard not to get excited about stage2.
Yes it probably will. The assumption is that the source of all types of Tinnitus are hyper active neurons firing signals in the brain. Other treatments in the works like Hair Cell Regeneration have requirements like non mechanical damage etc. because these target the inner ear hair cells and if someone has experienced mechanical damage (baratrauma) then there won't be anything wrong with the hair cells, where as AUT00063 will target the brain and like others say it will stop Tinnitus at the source. This is all if it actually ends up working out, and I'm really hoping this treatment will.
I hate to be a Debby Downer but as I've said before we need to exercise some caution. Many drugs fail in clinical trials, especially drugs that are "novel' such as the AUT000063 compound. We have no idea what the efficacy data looks like, and they really haven't published a whole lot of data even regarding what they did with the rats in question. It will be interesting to see. I am definitely hopeful it will be an effective treatment, but I am not going to hold my breath. Keep in mind that "cures" in the medical field are far and few between. What is much more likely is an effective treatment. That means we would probably have to keep taking this pill for life, or our tinnitus would return. As with any psychoactive compound, I can't imagine that it will be side effect free either. I'm also going to go out on a limb and wager that the pill will not make tinnitus disappear totally either, but reduce or greatly reduce it instead. All of that aside, I definitely would line up and take part in a trial if they would let me.
I feel like if autifony doesn't work for anyone or if it gets discontinued for safety reasons, i will likely descend into abject hopelessness. It feels like i have my whole life riding on this, because habituation isn't happening and i've completely lost my ability to relax. I haven't felt rested in more than two years now, which is really bad if you have chronic mental illness. Autifony or bust. Im done coping, now its time to treat my illness which has needed to be treated since day one. Two years has taught me that im not gonna get anywhere if they can't make this shit any fucking quieter. I give up.
Ya man I agree unfortunately. They said on their website, "lots of people would pay big money to be able to get rid of tinnitus, or even reduce the loudness by 50% ." Even hair cell regeneration is said to be only partially effective. All we can do is hope.
Have you sought help from a psychiatrist or tinnitus specialist? There is no need to suffer while we wait for treatments to come along. There is help out there which can be more effective than you think.
@Hudson,
"We have no idea what the efficacy data looks like, and they really haven't published a whole lot of data even regarding what they did with the rats in question."
In the current study, 20 Long Evans rats (and 10 sham controls) were exposed to a unilateral 116 dB, 16 kHz octave-band noise for one hour in order to induce temporary hearing loss and chronic tinnitus. Thirty days after the noise exposure, a subset of approximately half of the noise-exposed rats demonstrated deficits in auditory gap processing, consistent with the presence of tinnitus. All 30 rats were administered 30 and 60 mg/kg of AUT3 (a Kv3.1 positive modulator) and vehicle in a counterbalanced order, with 48-hours washout between treatments. Both the 30 and 60 mg/kg doses of AUT3 abolished evidence of tinnitus, while the drug had no effect on the behavior of control animals or noise-exposed animals without tinnitus.
_________________________________
Not that it really matters, but I'm just curious - What kind of data do you think they haven't included?
Also, can you show me any published pre-clinical rat models (like this one) of any other previous tinnitus drug trial?
(ie.Neramexane, Campral, AM101, Caroverine, etc etc)
"We have no idea what the efficacy data looks like, and they really haven't published a whole lot of data even regarding what they did with the rats in question."
In the current study, 20 Long Evans rats (and 10 sham controls) were exposed to a unilateral 116 dB, 16 kHz octave-band noise for one hour in order to induce temporary hearing loss and chronic tinnitus. Thirty days after the noise exposure, a subset of approximately half of the noise-exposed rats demonstrated deficits in auditory gap processing, consistent with the presence of tinnitus. All 30 rats were administered 30 and 60 mg/kg of AUT3 (a Kv3.1 positive modulator) and vehicle in a counterbalanced order, with 48-hours washout between treatments. Both the 30 and 60 mg/kg doses of AUT3 abolished evidence of tinnitus, while the drug had no effect on the behavior of control animals or noise-exposed animals without tinnitus.
_________________________________
Not that it really matters, but I'm just curious - What kind of data do you think they haven't included?
Also, can you show me any published pre-clinical rat models (like this one) of any other previous tinnitus drug trial?
(ie.Neramexane, Campral, AM101, Caroverine, etc etc)
I knew about the rat trials published and shown at the 2013 TRI. My point was that we have no efficacy data regarding humans yet. Animal data is great, and it is a starting point to justify exploration of a compound in human safety trials, but Long Evans rats and people are very different. The behavioral models in animals that are used to establish the presence of tinnitus are not without skepticism in the research community. Subjective tinnitus is not something which is easily measured. We can't ask the rats if they have tinnitus, just train them not to respond to certain stimuli and then we record when they don't jump when that stimuli is stopped. There is a healthy amount of argument as to whether that actually is evidence of tinnitus, or behavioral differences in the animals.
I'm not attacking animal models of tinnitus. I think it's great that they have been developed, as it has enabled tinnitus research more in the last 10 years than anything before it. I just think that a paper like that is hardly solid evidence that the compound abolishes tinnitus.
I'm just trying to say that people should not get their hopes up. I am hopeful for this compound, as it theoretically addresses chronic tinnitus. We don't really have any human data yet, and that's where this thing will either be made or broken. Until then, I maintain guarded optimism.
I thought they had a pretty good methodology for feeling like they really had induced T effectively in rats? Obviously there's no way to ask them and to know for sure. And that's sort of what all the optimism is riding on. It sure would be a waste if they didn't even know that much halfway for sure. I guess have to try it and see.
Well, if those rats really did have T, and they were indeed cure completely.... That would be wonderful. I guess that's what the world will be waiting to see in these Phase II trials. But the months/years it will take for them to be finished is too long for anyone to hold their breath over anyway.
So if this does work, and the rats were cured, will it be instant relief for T humans? You take the pill, and it's gone? Or reduced - just like that?
Well, if those rats really did have T, and they were indeed cure completely.... That would be wonderful. I guess that's what the world will be waiting to see in these Phase II trials. But the months/years it will take for them to be finished is too long for anyone to hold their breath over anyway.
So if this does work, and the rats were cured, will it be instant relief for T humans? You take the pill, and it's gone? Or reduced - just like that?
I have a feeling that Autifony already knows if this thing can cure a human. I am a conspiracy theory fan.
I agree with hudson although im really excited to hear more bout the results on humans, but what im worried Bout is that rats are alot smaller then humans even there brains and i dont know if it matters like he said we cant ask the rats ourselves, but if it did "cure" the rats T, then say humans take it and since were bigger it would only have a partial or no effect on us. Guess will see! Wish theyd take prisoners on death row like few monthes or years before there execution and test it on them rather then rats.
bill 112
Member
Bit confused here but what do people mean by mechanical damage are they referring to middle ear damage??
I think so. Which is different I suppose than cochlear damage.
They'd have to give them T first. Which would constitute cruel and unusual punishment.
In any case, while it certainly remains quite unproven, I'd like to think the geniuses at Autifony are mainly confident on the theoretical level, and so while no one really knows for absolute sure if the rats had T or not, or if they were cured or not, the concept is hopefully as strong as ever. And the concept is what is driving their optimism.
From what leading researchers are saying - they are pretty damned sure that the rats had tinnitus.
Here is an article as an example: (by the way Autifony is a KCNQ potassium modulator)---
Hearing Journal:
June 2013 - Volume 66 - Issue 6 - [no page #]
doi: 10.1097/01.HJ.0000430896.05545.73
Article
Noise-Induced Tinnitus Linked to Lower Potassium Channel Activity
Hogan, Michelle
Free Access
New research has identified a particular cellular mechanism associated with the induction of tinnitus in an animal model, representing an important step forward in the effort to better understand and treat this common auditory disorder.
"What had been known from others and our work is that once mice are exposed to loud sounds, some of them develop tinnitus, and the ones that develop tinnitus have hyperactive auditory systems," said Thanos Tzounopoulos, PhD, senior author of the study, which was published in Proceedings of the National Academy of Sciences.
"We wanted to figure out the cellular mechanism that leads to this hyperactivity," said Dr. Tzounopoulos, who is associate professor of otolaryngology and neurobiology at the University of Pittsburgh.
In the study, 51.4 percent of 35 mice exposed to noise showed behavioral evidence of tinnitus. Using brain slices that contained the dorsal cochlear nucleus—an auditory brainstem nucleus previously implicated in tinnitus induction—Dr. Tzounopoulos and colleagues showed a reduction in KCNQ potassium channel activity in mice with tinnitus compared with control mice and mice who did not develop tinnitus after noise exposure. This decreased activity was restricted to the same regions that showed tinnitus-specific hyperactivity—those sensitive to high-frequency sounds.
Retigabine, which is approved as an antiseizure drug, enhances the activation of the KCNQ channel. When noise-exposed mice were injected with this agent 30 minutes after noise exposure and then twice a day for five days, the percentage that developed tinnitus went down to 18.8 percent.
IN VIVO TESTING
"I think it's a very good paper," said Susan Shore, PhD, when asked to comment on the study. Dr. Shore is professor in the departments of otolaryngology, molecular and integrative physiology, and biomedical engineering at the University of Michigan.
"It's very systematic, and it's exploring the possible underlying mechanism that may contribute to tinnitus in these mice," she added.
Dr. Shore noted the limitation inherent in drawing conclusions from experiments done in slices.
"This is a particular technique where just a little slice of the brain is taken away from the rest of the brain and put in a medium where they can block other neurotransmitters and modulators, for example, that you don't do when you're recording in a live preparation, so I think that it's essential for these results to be replicated in an in vivo preparation where normal neuroplasticity and synaptic inputs from many other places are interacting with these cells," she said.
WINDOW OF OPPORTUNITY
The finding that retigabine suppressed tinnitus-like behaviors in this animal model is very provocative, said Richard Salvi, PhD, when asked to comment on the research.
"It's a pretty important study because it identifies an ion channel that regulates neuronal excitability, and this channel can be modulated by drugs that might be able to suppress tinnitus," said Dr. Salvi, who is SUNY distinguished professor in the department of communicative disorders and sciences, as well as director of the Center for Hearing and Deafness, at the University at Buffalo, the State University of New York.
The research suggests areas for future investigation, Dr. Salvi added, such as whether the approach works in other animal models.
"Can you suppress tinnitus induced by ototoxic drugs that induce hearing loss, for example? Are there other behavioral models that really confirm these results? Does this drug retigabine or analogs of this drug suppress tinnitus in humans?
"One of the issues that comes up in the tinnitus literature is whether tinnitus is one unitary phenomenon or whether there are many different types of tinnitus. We used to think at one time there was just one type of cancer, but now we know there are many different types of cancer, and drugs that might be effective in treating one type of cancer might not be effective in treating another type.
"Is this mechanism that they identified common to all forms of tinnitus, or just noise-induced tinnitus?"
There's also a matter of timing.
"Something you would wonder about is, if somebody's had tinnitus for a year or two, or if an animal's had tinnitus for one or two years, can the drug still suppress tinnitus, or is it no longer effective?" Dr. Salvi said. "That would be a future study."
Dr. Tzounopoulos and colleagues plan to address another question related to timing.
"There's a tiny window in which you can manipulate the channel and prevent the development of tinnitus," Dr. Tzounopoulos said. "We want to determine this window; we want to see how much time we have to interfere before tinnitus becomes permanent."
The researchers also plan to collaborate with chemists on developing more specific compounds that affect only the subunits of the KCNQ channel implicated in tinnitus, he said.
"About 50 percent of the mice who are exposed to a loud sound develop tinnitus and this downregulation in the channel. The question is, what determines which ones get it and which ones don't? We want to figure out if there is any protection to the ones that don't get it, or if there's some compensation that occurs there. These are the immediate things we're looking at right now."
HJ Return to thehearingjournal.com
© 2013 Lippincott Williams & Wilkins, Inc.
Article Outline
Here is an article as an example: (by the way Autifony is a KCNQ potassium modulator)---
Hearing Journal:
June 2013 - Volume 66 - Issue 6 - [no page #]
doi: 10.1097/01.HJ.0000430896.05545.73
Article
Noise-Induced Tinnitus Linked to Lower Potassium Channel Activity
Hogan, Michelle
Free Access
New research has identified a particular cellular mechanism associated with the induction of tinnitus in an animal model, representing an important step forward in the effort to better understand and treat this common auditory disorder.
"What had been known from others and our work is that once mice are exposed to loud sounds, some of them develop tinnitus, and the ones that develop tinnitus have hyperactive auditory systems," said Thanos Tzounopoulos, PhD, senior author of the study, which was published in Proceedings of the National Academy of Sciences.
"We wanted to figure out the cellular mechanism that leads to this hyperactivity," said Dr. Tzounopoulos, who is associate professor of otolaryngology and neurobiology at the University of Pittsburgh.
In the study, 51.4 percent of 35 mice exposed to noise showed behavioral evidence of tinnitus. Using brain slices that contained the dorsal cochlear nucleus—an auditory brainstem nucleus previously implicated in tinnitus induction—Dr. Tzounopoulos and colleagues showed a reduction in KCNQ potassium channel activity in mice with tinnitus compared with control mice and mice who did not develop tinnitus after noise exposure. This decreased activity was restricted to the same regions that showed tinnitus-specific hyperactivity—those sensitive to high-frequency sounds.
Retigabine, which is approved as an antiseizure drug, enhances the activation of the KCNQ channel. When noise-exposed mice were injected with this agent 30 minutes after noise exposure and then twice a day for five days, the percentage that developed tinnitus went down to 18.8 percent.
IN VIVO TESTING
"I think it's a very good paper," said Susan Shore, PhD, when asked to comment on the study. Dr. Shore is professor in the departments of otolaryngology, molecular and integrative physiology, and biomedical engineering at the University of Michigan.
"It's very systematic, and it's exploring the possible underlying mechanism that may contribute to tinnitus in these mice," she added.
Dr. Shore noted the limitation inherent in drawing conclusions from experiments done in slices.
"This is a particular technique where just a little slice of the brain is taken away from the rest of the brain and put in a medium where they can block other neurotransmitters and modulators, for example, that you don't do when you're recording in a live preparation, so I think that it's essential for these results to be replicated in an in vivo preparation where normal neuroplasticity and synaptic inputs from many other places are interacting with these cells," she said.
WINDOW OF OPPORTUNITY
The finding that retigabine suppressed tinnitus-like behaviors in this animal model is very provocative, said Richard Salvi, PhD, when asked to comment on the research.
"It's a pretty important study because it identifies an ion channel that regulates neuronal excitability, and this channel can be modulated by drugs that might be able to suppress tinnitus," said Dr. Salvi, who is SUNY distinguished professor in the department of communicative disorders and sciences, as well as director of the Center for Hearing and Deafness, at the University at Buffalo, the State University of New York.
The research suggests areas for future investigation, Dr. Salvi added, such as whether the approach works in other animal models.
"Can you suppress tinnitus induced by ototoxic drugs that induce hearing loss, for example? Are there other behavioral models that really confirm these results? Does this drug retigabine or analogs of this drug suppress tinnitus in humans?
"One of the issues that comes up in the tinnitus literature is whether tinnitus is one unitary phenomenon or whether there are many different types of tinnitus. We used to think at one time there was just one type of cancer, but now we know there are many different types of cancer, and drugs that might be effective in treating one type of cancer might not be effective in treating another type.
"Is this mechanism that they identified common to all forms of tinnitus, or just noise-induced tinnitus?"
There's also a matter of timing.
"Something you would wonder about is, if somebody's had tinnitus for a year or two, or if an animal's had tinnitus for one or two years, can the drug still suppress tinnitus, or is it no longer effective?" Dr. Salvi said. "That would be a future study."
Dr. Tzounopoulos and colleagues plan to address another question related to timing.
"There's a tiny window in which you can manipulate the channel and prevent the development of tinnitus," Dr. Tzounopoulos said. "We want to determine this window; we want to see how much time we have to interfere before tinnitus becomes permanent."
The researchers also plan to collaborate with chemists on developing more specific compounds that affect only the subunits of the KCNQ channel implicated in tinnitus, he said.
"About 50 percent of the mice who are exposed to a loud sound develop tinnitus and this downregulation in the channel. The question is, what determines which ones get it and which ones don't? We want to figure out if there is any protection to the ones that don't get it, or if there's some compensation that occurs there. These are the immediate things we're looking at right now."
HJ Return to thehearingjournal.com
© 2013 Lippincott Williams & Wilkins, Inc.
Article Outline
Retigabine hey? They're saying there's only a small window of opportunity. I really hope this isn't true but this seems to be well known by many scientists, so waiting around doesn't seem to be an option anymore. Is this the drug that was tested in phase 1?
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