Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus
- Thread starter attheedgeofscience
- Start date
Member
I beg to differ, one of the chief architects of TRT, maintained that TRT cured tinnitus, and of course this claim was taken up by the TRT lobby. Of course they are more modest in their claims now. Then the TRT people used to say there is no need for a cure. Of course they might say now they 'want to see a cure or an effective treatment but there will never be one.'
Anyway I dont want to pollute this thread any more with discussion of TRT.
Suffice to say this initiative by AOHL and Autifony and Newcastle Uni is a great one.
I can completely understand how anyone with moderate/severe tinnitus can be annoyed by suggestions that TRT can help them - when all they want is to get rid of sound instead of getting used to it.
I think even in world where we get something that lowers volume for lets say 75% (like in Corrine case) or even modest 30% - there still will be place for TRT and other developed therapies as I think people that lived with severe tinnitus (or moderate but had trouble handling it) - can suffer from some sort of lets call it ptsd (will T come back, i hope this med wont stop working after month, what if T volume increases anyway etc.) and what we have now will be very helpful in psychological component of T suffering to completely remove any shackles we've been put by circumstances that led to T.
jeannie
Member
- Nov 2, 2013
- 429
- Tinnitus Since
- 2013
- Cause of Tinnitus
- Noise-induced, Ear Infection, Medication... Who knows?
Chelles, I think he just gave her a quick kiss which im sure its happened to a lot of people, and it just happened to damage her ear, ive had it done to me before..
Why would anyone want to kiss your ear canal? Call me old fashion but making out with ears isn't cute!
I think I saw that on family guy haha.
But then you ended up with tinnitus down the line??!?
Kiss on the ear generates enough of a pressure gradient to move the stapes with a much bigger amplitude than it does for regular sound waves. The stapes effectively ''stabs'' the oval window creating a disturbance in the cochlear fluid as @dan mentioned.
Last time I checked air pressure related injuries are called barotrauma. I'm not sure who's trying to spread misinformation here, trying to claim kisses on the ear are completely harmless by anecdotal evidence. By all means then, carry on with your ear kissing. I sure as hell won't.
Why is it so important? We know that people without hearing damage acquire tinnitus and others not. I understand that we want to know the cause, so we'd know if the pill is effective for noise induced T, but even if that's not the reason, a good result is still s good one....
This is really getting silly. Stop littering the thread with garbage about "Can you get tinnitus from a kiss on the ear."
People get tinnitus from the weirdest things. Someone got it from blowing their nose to hard, someone got it from having a cold, someone got it from having their skull fractured in a car accident (yeah I met a guy that had the left side of his skull bashed in, had some big scars too. He couldn't hear a thing on his left ear except a tinnitus made straight from Hell however he was a pretty happy dude anyway).
What we have here is ONE anecdotal testimony of an experimental drug. It's just the one. Not one million, ONE!
So just take it for what it is. It's good news of course and it certainly brings hope, however it's not proof that the drug works. How she got the tinnitus is of little importance at this point. And now I'm sure some people will reply to me and say: "Well, sure it matters, I want to know if it will work for my tinnitus."
That you might find out if you get into the phase III or when the drug eventually enters the market. Because once again, it is one testimony. ONE! If we had 100 testimonials then it might be of importance as to how those people got their tinnitus and what category they might belong to. But for now. IT DOES NOT MATTER!
People get tinnitus from the weirdest things. Someone got it from blowing their nose to hard, someone got it from having a cold, someone got it from having their skull fractured in a car accident (yeah I met a guy that had the left side of his skull bashed in, had some big scars too. He couldn't hear a thing on his left ear except a tinnitus made straight from Hell however he was a pretty happy dude anyway).
What we have here is ONE anecdotal testimony of an experimental drug. It's just the one. Not one million, ONE!
So just take it for what it is. It's good news of course and it certainly brings hope, however it's not proof that the drug works. How she got the tinnitus is of little importance at this point. And now I'm sure some people will reply to me and say: "Well, sure it matters, I want to know if it will work for my tinnitus."
That you might find out if you get into the phase III or when the drug eventually enters the market. Because once again, it is one testimony. ONE! If we had 100 testimonials then it might be of importance as to how those people got their tinnitus and what category they might belong to. But for now. IT DOES NOT MATTER!
Sadly, we won't get many testimonials as their strict requirements impede us tt members from getting on. I know I can't go on, I would've loved to have mixed trobalt with Autifony's drug, to see what would've happened...Damn them.
We better hope Autifony pulls through as trobalt is far from safe and people are taking risks, I know I am, from taking this monster. I just hope this drug does pull through, as there isn't much else.
You would NOT be allowed to mix Aut063 with Trobalt during the trial because that would taint the experiment by introducing another variable.
Why would you want to do such a thing? If the drug is ever released it will mean it works... Unless we talk about another maybe, "works for some not for others"or "Tinnitus is complicated" that kind of thing...
Getting really tired of all these. Why would anybody want to keep on trying such cocktails? It will only mean these drugs don't work.
We need a cure, not a temporary drug that may help. If these trials end up to that kind of "maybe", AUT00063 will never hit the market, naturally. And if that is the case, perhaps it shouldn't. It wil be a sad, but simple conclusion one should come up with, if Trobalt is still used for T 5 years from now. Really really sad!
http://www.investopedia.com/articles/investing/060215/top-10-pfizer-venture-investments.asp
CytomX is a San Francisco-based biotechnology company engaged in creating Probody therapeutics for cancer treatment. Probodies are recombinant antibodies designed to focus on diseased tissue but remain inert in healthy tissues in the body. CytomX is seeking to develop new immunotherapies.
2. Ablexis
Ablexis is one of Pfizer Venture Investments' early-stage major investments. The company, located in San Francisco, California, is developing a transgenic mouse platform, AlivaMab Mouse, for use in discovering and developing therapeutic antibodies to treat a wide variety of diseases.
3. Autifony
Headquartered in London in the United Kingdom, Autifony is one of Pfizer Venture Investments' few major investments in non-U.S. based firms. Autifony is devoted to developing new medicines to treat hearing disorders. The company's current lead project undergoing testing is a new drug that targets basic auditory processing in the brain.
Autifony recently bagged a £5 million investment from Pfizer Venture Investments as well as funding from the International Biotechnology Trust, to join existing investors SV Life Sciences, Imperial Innovations plc and UCL Business plc in the Series A financing round, bringing the total raised to date to £15.75 million.
CytomX is a San Francisco-based biotechnology company engaged in creating Probody therapeutics for cancer treatment. Probodies are recombinant antibodies designed to focus on diseased tissue but remain inert in healthy tissues in the body. CytomX is seeking to develop new immunotherapies.
2. Ablexis
Ablexis is one of Pfizer Venture Investments' early-stage major investments. The company, located in San Francisco, California, is developing a transgenic mouse platform, AlivaMab Mouse, for use in discovering and developing therapeutic antibodies to treat a wide variety of diseases.
3. Autifony
Headquartered in London in the United Kingdom, Autifony is one of Pfizer Venture Investments' few major investments in non-U.S. based firms. Autifony is devoted to developing new medicines to treat hearing disorders. The company's current lead project undergoing testing is a new drug that targets basic auditory processing in the brain.
Autifony recently bagged a £5 million investment from Pfizer Venture Investments as well as funding from the International Biotechnology Trust, to join existing investors SV Life Sciences, Imperial Innovations plc and UCL Business plc in the Series A financing round, bringing the total raised to date to £15.75 million.
Noise trauma from a tinny stereo in a small room after the third time over three Saturdays.
That's fine @Nucleo , I didn't say you were wrong with the ear kisses, I asked for evidence which you have given me, I can live with that and was nothing much to do with the crux of my reply to you anyway!
Your statement that I took issue with was, and I quote."Suctioning causes barotrauma." I have exposed that as wrong, and I notice you haven't retracted it or bothered to even touch the subject in your answering post, stating your opinions like they are fact is damaging, not helpful and a little irresponsible and could even stop someone from getting the medical help that they may need.
That is all I have to say on this as it is derailing this thread!
Good to see Autifony is getting increased funding.
I am very keen on the objective measure being developed with AOHL Newcatle Uni etc, athough that is not a prerequisite for the trials. The objective measure will be universally beneficial once developed.
A few questions:
When au0063 was first evaluated in rodents, did they used gap detection as a means of showing that it worked. How reliable is this in rodents? What are the reasons this does not work in humans?
Why does it take from July to the end of the year to evaluate the results. Why can this not be expedited?
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
Consider posting your questions in the Q&A-session thread before the deadline passes in two days:
www.tinnitustalk.com/threads/autifony-q-a.8331
This is easy to read article about K channels and relevance to tinnitus:
http://www.medicalnewstoday.com/articles/245357.php
http://www.medicalnewstoday.com/articles/245357.php
I have dual citizenship. US and EU. I live in the US but have means of setting up shop in the UK if need be. If I establish residency in the UK and get a GP I believe I could qualify and participate in this trial. Does this sound correct to you all?
I meet all other criteria. Thoughts?
I meet all other criteria. Thoughts?
Bear in mind,you could do all that,and still have a 50 per cent chance of getting the placebo!Might be easier to hold on a little while longer and wait for results to be published
Somewhere in the other Autifony thread I guess. This thread is the second one about phase 2. Here's the first one:
https://www.tinnitustalk.com/thread...-treatment-of-hearing-loss-and-tinnitus.1607/
umm, yes its pretty reliabe on rodents but because humans dont need water licking gap detection tests, we can just say if we hear T or not, it does not work on humans
umm, yes its pretty reliabe on rodents but because humans dont need water licking gap detection tests, we can just say if we hear T or not, it does not work on humans
I believe there has been some recent papers on the differences between rodents and human regading perception of tinnitus based on gap detection, just wanted to know a bit more about this and implications.
I wasnt aware of that
I dont want to startle reflex you: , but there is a lot of gaps to be filled here. The paper below is from 2014, I saw a couple of papers from this year
http://www.hindawi.com/journals/np/2014/741452/
The ultimate benchmark for any animal model measuring subjective tinnitus is comparability to the human patient. Any researcher starting to model tinnitus in laboratory animals has to make a decision regarding the species, the method of tinnitus induction, and the behavioral test. The current review provides an overview over the most commonly used methods and approaches.
The most important criteria for choosing a certain species is its hearing range, its aptitude for behavioral studies and the availability of genetically modified strains. These strains allow the recording and manipulation of specific types of neurons revealing their role in tinnitus. The behavioral differences between the commonly used species are a source of uncertainty. The majority of studies discussed here were done in rats, considered to be well suited for behavioral testing even with more difficult sensory decision making paradigms [130]. Another advantage of the rat as an experimental model for studying the neuronal circuitry underlying tinnitus is the possibility to implant electrode arrays with high channel counts and perform chronic recordings in awake [131] and behaving animals (e.g., Otazu and Zador [132]). The disadvantage of the rat as a model is its high-frequency hearing range, which differs significantly from the human one. Still, it remains unclear so far if these differences in hearing rage are significant for the pathogenesis, perception, and potential therapy of tinnitus. Additionally, there are only a limited number of genetically modified rat strains available. However, this last factor is certainly changing in the future as more and more recombinase-driver rat lines are developed (e.g., [133]) and the establishment of the potentially universally applicable CRISPR genome-editing technique [134], which has already been applied successfully in cynomolgus monkey (Macaca fascicularis) [135].
The tinnitus induction protocol should model the human pathogenesis. For the majority of human cases, an acoustic trauma-induced hearing loss is suspected. This favors a tinnitus induction through acoustic trauma over a pharmacological induction. On the other hand, an induction through salicylate has the advantage of fast onset of tinnitus and its reversibility. This allows a behavioral setting that can be controlled for tinnitus related behavioral peculiarities of individual animals. Furthermore, salicylate can be applied locally which allows to study tinnitus-related changes at different stages of the auditory processing hierarchy. Whichever method is used, the accompanying hearing loss and hyperacusis have to be taken into account for interpreting the results. However, to disentangle tinnitus and hyperacusis is very challenging as they are comorbid. Very recently, it has been demonstrated that mice exposed to "neuropathic" noise displayed a hyperresponsivity to acoustic startle stimuli. At the same time the gap detection deficits (measured as prepulse inhibition of the startle response) were limited to certain gap-stimulus latencies which cannot be explained by the presence of a phantom sound which should fill the gap for all latencies [107] and which therefore has be interpreted as a potential indicator of hyperacusis.
The behavioral approaches testing for subjective tinnitus presented here include paradigms using reflexes, Pavlovian conditioning, and operant conditioning. Tinnitus in humans is a conscious percept which involves the auditory cortex [120]. It is usually measured through sensory decision making tests which can be applied over extended periods. A behavioral test for laboratory animals should be shaped along these aspects, in particular the cortical involvement and extended testing period. Additionally, such a test should only require limited training periods in order to achieve a high throughput. For conditioned responses the auditory cortex is not essential, as a cortical ablation does not prevent an animal from a classical conditioning response to simple tones [105]. However, more complex tones (e.g., frequency modulated tones) necessarily require a functional auditory cortex for discrimination [136]. More complex operant conditioning tasks most likely rely on an intact auditory cortex [105]. This has to be balanced with the usually more time consuming training protocols required for operant conditioning paradigms. For the conditioning paradigms introduced here, an involvement of the auditory cortex has not been shown yet, leaving an explanatory gap between the observed behavior and its neuronal substrate. Furthermore, modulation of the tinnitus percept through higher cognitive functions as demonstrated in humans (e.g., attention [137]) has been ignored in animal studies so far, most likely due to a lack of behavioral paradigms allowing the manipulation of these functions. However, a comprehensive animal model should ideally take this factor into account as well.
http://www.hindawi.com/journals/np/2014/741452/
The ultimate benchmark for any animal model measuring subjective tinnitus is comparability to the human patient. Any researcher starting to model tinnitus in laboratory animals has to make a decision regarding the species, the method of tinnitus induction, and the behavioral test. The current review provides an overview over the most commonly used methods and approaches.
The most important criteria for choosing a certain species is its hearing range, its aptitude for behavioral studies and the availability of genetically modified strains. These strains allow the recording and manipulation of specific types of neurons revealing their role in tinnitus. The behavioral differences between the commonly used species are a source of uncertainty. The majority of studies discussed here were done in rats, considered to be well suited for behavioral testing even with more difficult sensory decision making paradigms [130]. Another advantage of the rat as an experimental model for studying the neuronal circuitry underlying tinnitus is the possibility to implant electrode arrays with high channel counts and perform chronic recordings in awake [131] and behaving animals (e.g., Otazu and Zador [132]). The disadvantage of the rat as a model is its high-frequency hearing range, which differs significantly from the human one. Still, it remains unclear so far if these differences in hearing rage are significant for the pathogenesis, perception, and potential therapy of tinnitus. Additionally, there are only a limited number of genetically modified rat strains available. However, this last factor is certainly changing in the future as more and more recombinase-driver rat lines are developed (e.g., [133]) and the establishment of the potentially universally applicable CRISPR genome-editing technique [134], which has already been applied successfully in cynomolgus monkey (Macaca fascicularis) [135].
The tinnitus induction protocol should model the human pathogenesis. For the majority of human cases, an acoustic trauma-induced hearing loss is suspected. This favors a tinnitus induction through acoustic trauma over a pharmacological induction. On the other hand, an induction through salicylate has the advantage of fast onset of tinnitus and its reversibility. This allows a behavioral setting that can be controlled for tinnitus related behavioral peculiarities of individual animals. Furthermore, salicylate can be applied locally which allows to study tinnitus-related changes at different stages of the auditory processing hierarchy. Whichever method is used, the accompanying hearing loss and hyperacusis have to be taken into account for interpreting the results. However, to disentangle tinnitus and hyperacusis is very challenging as they are comorbid. Very recently, it has been demonstrated that mice exposed to "neuropathic" noise displayed a hyperresponsivity to acoustic startle stimuli. At the same time the gap detection deficits (measured as prepulse inhibition of the startle response) were limited to certain gap-stimulus latencies which cannot be explained by the presence of a phantom sound which should fill the gap for all latencies [107] and which therefore has be interpreted as a potential indicator of hyperacusis.
The behavioral approaches testing for subjective tinnitus presented here include paradigms using reflexes, Pavlovian conditioning, and operant conditioning. Tinnitus in humans is a conscious percept which involves the auditory cortex [120]. It is usually measured through sensory decision making tests which can be applied over extended periods. A behavioral test for laboratory animals should be shaped along these aspects, in particular the cortical involvement and extended testing period. Additionally, such a test should only require limited training periods in order to achieve a high throughput. For conditioned responses the auditory cortex is not essential, as a cortical ablation does not prevent an animal from a classical conditioning response to simple tones [105]. However, more complex tones (e.g., frequency modulated tones) necessarily require a functional auditory cortex for discrimination [136]. More complex operant conditioning tasks most likely rely on an intact auditory cortex [105]. This has to be balanced with the usually more time consuming training protocols required for operant conditioning paradigms. For the conditioning paradigms introduced here, an involvement of the auditory cortex has not been shown yet, leaving an explanatory gap between the observed behavior and its neuronal substrate. Furthermore, modulation of the tinnitus percept through higher cognitive functions as demonstrated in humans (e.g., attention [137]) has been ignored in animal studies so far, most likely due to a lack of behavioral paradigms allowing the manipulation of these functions. However, a comprehensive animal model should ideally take this factor into account as well.
But I meant that they maybe are linked somewhere in the thread. Phase 1 was just for safety and tested on people without T. There arent any "results" to talk about anyway other than that the drug was considered safe enough to go through to phase 2.
Phase I trial only tests healthy volounteers for safety, dosage and side effect assessment of the drugs.
That is crazy if they test the drug with healty volounteers maybe they become tinnitus sufferes !
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