At least we create a competition between Chinese labs and autifony in order to have this drug on the market as soon as possible.
Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus
- Thread starter attheedgeofscience
- Start date
At least we create a competition between Chinese labs and autifony in order to have this drug on the market as soon as possible.
Member
This is why medicine took huge leaps in the second world war. The german mad doctors and scientists had plenty of subjects and no regulation.
Yeah, they were mental! Although, hitler's personal doctor was just bat mad.
Here is a bit from the patent on tinnitus
Hearing loss represents an epidemic that affects approximately 16% of the population in Europe and the US (Goldman and Holme, 2010, Drug Discovery Today 15, 253-255), with a prevalence estimated at 250 million people worldwide (B. Shield, 2006, Evaluation of the social and economic costs of hearing impairment. A report for Hear-It AISBL: www.hear-it.org/multimedia/Hear It Report October 2006.pdf). As life expectancy continues to increase, so too will the number of people suffering from hearing disorders. Furthermore, it is believed that modern lifestyles may exacerbate this burden as the younger generation ages. Hearing conditions, including tinnitus have a profound effect on the quality of life, causing social isolation, depression, work and relationship difficulties, low self-esteem, and prejudice. Voltage-gated ion channels of the Kv3 family are expressed at high levels in auditory brainstem nuclei (Li et al., 2001, J. Comp. Neurol. 437, 196-218) where they permit the fast firing of neurons that transmit auditory information from the cochlear to higher brain regions. Loss of Kv3.1 channel expression in central auditory neurons is observed in hearing impaired mice (von Hehn et al., 2004, J. Neurosci. 24, 1936-1940), and a decline in Kv3.1 expression may be associated with loss of hearing in aged mice (Jung et al. 2005 Neurol. Res. 27, 436-440). Furthermore, pathological plasticity of auditory brainstem networks is likely to contribute to symptoms of tinnitus that are experienced by many people suffering from hearing loss of different types. Recent studies have shown that regulation of Kv3.1 channel function and expression has a major role in controlling auditory neuron excitability (Kaczmarek et al., 2005, Hearing Res. 206, 133-145), suggesting that this mechanism could account for some of the plastic changes that give rise to tinnitus.
Hearing loss represents an epidemic that affects approximately 16% of the population in Europe and the US (Goldman and Holme, 2010, Drug Discovery Today 15, 253-255), with a prevalence estimated at 250 million people worldwide (B. Shield, 2006, Evaluation of the social and economic costs of hearing impairment. A report for Hear-It AISBL: www.hear-it.org/multimedia/Hear It Report October 2006.pdf). As life expectancy continues to increase, so too will the number of people suffering from hearing disorders. Furthermore, it is believed that modern lifestyles may exacerbate this burden as the younger generation ages. Hearing conditions, including tinnitus have a profound effect on the quality of life, causing social isolation, depression, work and relationship difficulties, low self-esteem, and prejudice. Voltage-gated ion channels of the Kv3 family are expressed at high levels in auditory brainstem nuclei (Li et al., 2001, J. Comp. Neurol. 437, 196-218) where they permit the fast firing of neurons that transmit auditory information from the cochlear to higher brain regions. Loss of Kv3.1 channel expression in central auditory neurons is observed in hearing impaired mice (von Hehn et al., 2004, J. Neurosci. 24, 1936-1940), and a decline in Kv3.1 expression may be associated with loss of hearing in aged mice (Jung et al. 2005 Neurol. Res. 27, 436-440). Furthermore, pathological plasticity of auditory brainstem networks is likely to contribute to symptoms of tinnitus that are experienced by many people suffering from hearing loss of different types. Recent studies have shown that regulation of Kv3.1 channel function and expression has a major role in controlling auditory neuron excitability (Kaczmarek et al., 2005, Hearing Res. 206, 133-145), suggesting that this mechanism could account for some of the plastic changes that give rise to tinnitus.
I found this-
Pharmacological modulation of Kv3.1 potassium currents Maile R. Brown1, Charles H. Large2, Giuseppe Alvaro2, Leonard K. Kaczmarek1 1Department of Pharmacology, Yale School of Medicine, New Haven, CT 2Autifony Therapeutics Ltd., Via Fleming 4, Verona, Italy Kv3-family potassium channels such as Kv3.1 are typically expressed in rapidly spiking neurons and in brain regions such as the auditory brainstem, where firing at high rates with high temporal accuracy is absolutely required for sensory processing. One characteristic that distinguishes these channels from other voltage-dependent potassium channels is their very rapid rate of activation and deactivation in response to transient depolarization. In addition, Kv3 channels typically activate only at positive potentials (>- 10mV). These features allow neurons to fire at high frequencies (up to ~800 Hz). Until now, manipulations of levels of Kv3 currents in neurons have required genetic manipulations or use of the non-specific potassium channel blocker tetraethylammonium ions (TEA). We now report that two imidazolidinedione derivatives, Compound 1 and Compound 2, specifically increase and decrease Kv3.1 currents respectively. Using CHO cells stably transfected with Kv3.1, we have found that 10μM Compound 1 shifts the voltage of activation of Kv3.1 currents towards negative potentials, producing as much as a 131.3% increase in current at membrane potentials close to -10mV. Numerical simulations of the firing properties of auditory brainstem neurons, predict that increasing concentrations of Compound 1 would be expected to decrease firing rate in response to high frequency stimulation (400 Hz), but to increase the temporal accuracy with which actions potentials are phase-locked to the stimuli. In contrast, the compound Compound 2 produced a sustained shift in voltage-dependence of inactivation to more negative potentials, as well as altering voltage-dependence of activation. Although Kv3.1 channels usually inactivate only very slowly during sustained depolarization, the rate of channel inactivation is also markedly increased in the presence of Compound 2. Thus the net effect of this compound is to suppress Kv3.1 currents in the physiological range of membrane potentials. In numerical simulations, Compound 2 had a biphasic effect on excitability. Low concentrations increased the rate of firing in response to 400 Hz stimulation whereas higher concentrations prevented neurons from responding to highfrequency stimulation, as is found in mice in which Kv3.1 has been deleted. Modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability. Theme and Topic: Potassium channels: Physiology Keyword: Kv3.1 POTASSIUM CHANNEL, excitability Support : Yes Grant/Other Support: Autifony Therapeutics Limited
Pharmacological modulation of Kv3.1 potassium currents Maile R. Brown1, Charles H. Large2, Giuseppe Alvaro2, Leonard K. Kaczmarek1 1Department of Pharmacology, Yale School of Medicine, New Haven, CT 2Autifony Therapeutics Ltd., Via Fleming 4, Verona, Italy Kv3-family potassium channels such as Kv3.1 are typically expressed in rapidly spiking neurons and in brain regions such as the auditory brainstem, where firing at high rates with high temporal accuracy is absolutely required for sensory processing. One characteristic that distinguishes these channels from other voltage-dependent potassium channels is their very rapid rate of activation and deactivation in response to transient depolarization. In addition, Kv3 channels typically activate only at positive potentials (>- 10mV). These features allow neurons to fire at high frequencies (up to ~800 Hz). Until now, manipulations of levels of Kv3 currents in neurons have required genetic manipulations or use of the non-specific potassium channel blocker tetraethylammonium ions (TEA). We now report that two imidazolidinedione derivatives, Compound 1 and Compound 2, specifically increase and decrease Kv3.1 currents respectively. Using CHO cells stably transfected with Kv3.1, we have found that 10μM Compound 1 shifts the voltage of activation of Kv3.1 currents towards negative potentials, producing as much as a 131.3% increase in current at membrane potentials close to -10mV. Numerical simulations of the firing properties of auditory brainstem neurons, predict that increasing concentrations of Compound 1 would be expected to decrease firing rate in response to high frequency stimulation (400 Hz), but to increase the temporal accuracy with which actions potentials are phase-locked to the stimuli. In contrast, the compound Compound 2 produced a sustained shift in voltage-dependence of inactivation to more negative potentials, as well as altering voltage-dependence of activation. Although Kv3.1 channels usually inactivate only very slowly during sustained depolarization, the rate of channel inactivation is also markedly increased in the presence of Compound 2. Thus the net effect of this compound is to suppress Kv3.1 currents in the physiological range of membrane potentials. In numerical simulations, Compound 2 had a biphasic effect on excitability. Low concentrations increased the rate of firing in response to 400 Hz stimulation whereas higher concentrations prevented neurons from responding to highfrequency stimulation, as is found in mice in which Kv3.1 has been deleted. Modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability. Theme and Topic: Potassium channels: Physiology Keyword: Kv3.1 POTASSIUM CHANNEL, excitability Support : Yes Grant/Other Support: Autifony Therapeutics Limited
- Aug 21, 2014
- 5,049
- Tinnitus Since
- 1999
- Cause of Tinnitus
- karma
I thought about this because I had a friend who did just this with the sleeping drug suvorexant, to get his hands on some before it hit the market.
I looked at the synthesis details in the patent, though -- this stuff (AUT0063) appears to be very difficult to make. I don't think I'd trust a chinese lab to get it right, and I don't know how one would verify their work without a sample of the real thing to do a mass spec comparison on.
- Aug 21, 2014
- 5,049
- Tinnitus Since
- 1999
- Cause of Tinnitus
- karma
No, it's not. It's not a GABAergenic, and I think it works on a receptor system that's not targeted by many/any other drugs. Check Wikipedia, I guess.
Oh, that's awesome! Does it work well for sleep? When will it come out in the UK?
Autifony have started recruting in Florida and Utah for their US trial of AUT00063. But the american trial is, as we know, mainly for hearing loss.
https://clinicaltrials.gov/ct2/show/NCT02345031
https://clinicaltrials.gov/ct2/show/NCT02345031
Age-Related Hearing Loss to be precise.
Which can only mean one thing: The drug is definitely suitable for chronic cases!
I disagree, after reading their -short-term study & it's purpose. "Reduced activity at certain sites in the brain (called "voltage-gated potassium channels") has been linked to hearing problems, like age-related loss of hearing or tinnitus (a 'ringing' or buzzing noise in the ears)."
It indicates for Comorbidity reasons/using chemicals for Mental illnesses; reduce anxiety.
Criteria is only for those with age-related hearing loss/T ONLY, whose T "existed for not less than 6 months, and not more than 18 months."
Ten Non-criterias: Example: Does not work for those (not-limited to) whose T is:
1. "...a concomitant symptom of a known otological condition (including but not limited to otitis externa, otitis media, otosclerosis, cholesteatoma, Ménière's disease or other vestibular problems, acoustic neuroma, or temporo-mandibular joint disorder)..." and
2. "Intermittent tinnitus (comes and goes from one day to the next".
3. ..."History of important cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases deemed clinically significant."
4. "Surgery or medical condition that might would be expected to significantly affect absorption of medicines"
etc etc etc.
Consequently, this rules out ANYONE with "chronic" T or cases.
FLA, the Senior State = age-related subjects are being recruited to ingest "Happy" brain-altering meds.
They set the criteria of no more than 18 months for trial purposes only. It is well established in their interviews, they want to limit the range of patients. It is my opinion once the drug hits the market it will do for all tinnitus sufferers.
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
I leave it as an exercise...
www.tinnitustalk.com/threads/autifony-therapeutics-phase-ii-study-for-aut00063-for-the-treatment-of-hearing-loss-and-tinnitus.6516/page-30#post-90363
[The answer is 1 - (1/2)^3 = 87,5% = 12,5% ("odds", or likelihood of all three getting the placebo - if indeed the split between placebo/drug is 50% to 50% which I believe it is for this trial).]
Still "3" is a low, low number (for other reasons, besides the "odds").
Interesting. And unusual, I believe. Never heard of that before with any trial, actually.
@attheedgeofscience I thought there were some people from the AM-101 phase 2 trials that were told *after* the trial concluded and results published.
I was told that if I inquire, that I'll probably find out *after* phase 3 is complete and the results are published.
I was told that if I inquire, that I'll probably find out *after* phase 3 is complete and the results are published.
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
Noted. Perhaps I read the line too literally i.e. "We may now be told..."
It sounded (to me) as if they would release the information while the trial was on-going. "That's what I meant..."
I know it's been commented on before, but quite unbelievable that 5 months into the trial and a potential 150 participants, only a couple have reported on this forum.
If I were selected and knew nothing about the background to the trial, I'd Google and find my way here and want to say something.
Entering 'Autifony clinical trial' into Google brings this thread up on page 2.
Maybe the strict selection criteria has excluded almost all potential participants.
If I were selected and knew nothing about the background to the trial, I'd Google and find my way here and want to say something.
Entering 'Autifony clinical trial' into Google brings this thread up on page 2.
Maybe the strict selection criteria has excluded almost all potential participants.
Well...They are finally doing a trial in America for hearing loss..http://www.autifony.com/autifony-age-related-hearing-loss-clinical-trial-sites.asp
So why do they still insist on this hearing loss component!?
I could not understand why the hearing loss component was included in the UK trial. According to Dr Roland Schaette, he seems to consider we all have "hidden" hearing loss
Well, because Autifony don't know how to conduct a proper trial lol I mean, they still haven't got all the people they need.
It would be great if they expand this to the quiet-1 trial, I could walk 5 minutes to one of the hospitals!
I emailed both hospitals near me and one doctor said yes the trials would be expanded to tinnitus and the other doctor said no......so it seems either they're guessing, making it up as they go along or just don't have all the information yet.
Well, I don't have a clue what they are doing...I think they believe their drug is a jack of all trades.
Log in or register to get the full forum benefits!
Similar threads
