Autifony Therapeutics Phase I Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus

[Mpt]

I'm copying this one post over from the retigabine thread because I think its relevant, and its possible some people on this thread might not see it... as many of you know I am a frequent poster and have suffered greatly with tinnitus for the past 5 months, and I've seen an improvement that I almost know with a 99% certainty is idue to this drug which is similar to autifony...

I have had a massive improvement a few days after getting on retigabine, but I wanted to give it awhile before reporting anything to reduce the chance that I'm reporting on a placebo effect. I've been taking it exactly two weeks as of today, and I can pretty confidently say that the improvement that I've seen is not a placebo effect or habituation. My tinnitus is/was pretty loud. Before taking the drug I was starting to habituate, but the sound hadn't changed, if anything when I checked it by sticking my fingers in my ears, it sounded louder than it originally was 5 months ago when I got tinnitus, my reaction was just better. Now though, I literally don't hear the ringing, its still there, but I can't even hear it in quiet rooms—I literally have to be in a quiet space and plug my ears in order to hear it, if I plug my ears in a room with decent ambient sound… air conditioning, tv.. I can't even hear it in those environments with my ears plugged. A few weeks ago I could hear it driving down the interstate at 80mph with the radio on. Retigabine is a potassium channel modulator KV7, (Autofony is a KV3 modulator). The brand name is Potiga in the US and Trobalt in Europe. My father-in-law is a gp and prescribed it for me off label. Obviously I'm going to keep taking it if these results persist. Thought you guys would want to know.
Tinnitus probably has different etiologies like other brain diseases, epilepsy, etc--- and yes it a disease--- that's like saying epilepsy isn't a disease, seizures are just a symptom, just a semantics debate for authorities within the tinnitus community to spin their agendas with… if anyone can get a Dr to give them this off label I think its worth a shot—I'll keep everyone updated

 

[Grace]

I'm copying this one post over from the retigabine thread because I think its relevant, and its possible some people on this thread might not see it... as many of you know I am a frequent poster and have suffered greatly with tinnitus for the past 5 months, and I've seen an improvement that I almost know with a 99% certainty is idue to this drug which is similar to autifony...

I have had a massive improvement a few days after getting on retigabine, but I wanted to give it awhile before reporting anything to reduce the chance that I'm reporting on a placebo effect. I've been taking it exactly two weeks as of today, and I can pretty confidently say that the improvement that I've seen is not a placebo effect or habituation. My tinnitus is/was pretty loud. Before taking the drug I was starting to habituate, but the sound hadn't changed, if anything when I checked it by sticking my fingers in my ears, it sounded louder than it originally was 5 months ago when I got tinnitus, my reaction was just better. Now though, I literally don't hear the ringing, its still there, but I can't even hear it in quiet rooms—I literally have to be in a quiet space and plug my ears in order to hear it, if I plug my ears in a room with decent ambient sound… air conditioning, tv.. I can't even hear it in those environments with my ears plugged. A few weeks ago I could hear it driving down the interstate at 80mph with the radio on. Retigabine is a potassium channel modulator KV7, (Autofony is a KV3 modulator). The brand name is Potiga in the US and Trobalt in Europe. My father-in-law is a gp and prescribed it for me off label. Obviously I'm going to keep taking it if these results persist. Thought you guys would want to know.
Tinnitus probably has different etiologies like other brain diseases, epilepsy, etc--- and yes it a disease--- that's like saying epilepsy isn't a disease, seizures are just a symptom, just a semantics debate for authorities within the tinnitus community to spin their agendas with… if anyone can get a Dr to give them this off label I think its worth a shot—I'll keep everyone updated

Was your T noise induced?!!!---- im happy for you! I hope it stays that wway for you! No side effects?

 

[Mpt]

yes and no-- i had my ears syringed and a few hours later while standing in my very loud shower (90db) a siren went off in my ear that I could hear over the shower- so I believe it was an interplay of the two

 

[benryu]

I'm copying this one post over from the retigabine thread because I think its relevant, and its possible some people on this thread might not see it... as many of you know I am a frequent poster and have suffered greatly with tinnitus for the past 5 months, and I've seen an improvement that I almost know with a 99% certainty is idue to this drug which is similar to autifony...

I have had a massive improvement a few days after getting on retigabine, but I wanted to give it awhile before reporting anything to reduce the chance that I'm reporting on a placebo effect. I've been taking it exactly two weeks as of today, and I can pretty confidently say that the improvement that I've seen is not a placebo effect or habituation. My tinnitus is/was pretty loud. Before taking the drug I was starting to habituate, but the sound hadn't changed, if anything when I checked it by sticking my fingers in my ears, it sounded louder than it originally was 5 months ago when I got tinnitus, my reaction was just better. Now though, I literally don't hear the ringing, its still there, but I can't even hear it in quiet rooms—I literally have to be in a quiet space and plug my ears in order to hear it, if I plug my ears in a room with decent ambient sound… air conditioning, tv.. I can't even hear it in those environments with my ears plugged. A few weeks ago I could hear it driving down the interstate at 80mph with the radio on. Retigabine is a potassium channel modulator KV7, (Autofony is a KV3 modulator). The brand name is Potiga in the US and Trobalt in Europe. My father-in-law is a gp and prescribed it for me off label. Obviously I'm going to keep taking it if these results persist. Thought you guys would want to know.
Tinnitus probably has different etiologies like other brain diseases, epilepsy, etc--- and yes it a disease--- that's like saying epilepsy isn't a disease, seizures are just a symptom, just a semantics debate for authorities within the tinnitus community to spin their agendas with… if anyone can get a Dr to give them this off label I think its worth a shot—I'll keep everyone updated

What was your dosage, great news !

 

[Mpt]

im taking 300 mg 3 times a day... i gradually worked up to that dosage

 

[Johno]

And it still helps? Are you feeling some adverse effects?

 

[benryu]

im taking 300 mg 3 times a day... i gradually worked up to that dosage

Ok so the standard dose, when do you plan to reduce the dose?

 

[john2012]

Now though, I literally don't hear the ringing, its still there, but I can't even hear it in quiet rooms—I literally have to be in a quiet space and plug my ears in order to hear it, if I plug my ears in a room with decent ambient sound… air conditioning, tv.. I can't even hear it in those environments with my ears plugged. A few weeks ago I could hear it driving down the interstate at 80mph with the radio on. Retigabine is a potassium channel modulator KV7, (Autofony is a KV3 modulator). The brand name is Potiga in the US and Trobalt in Europe.

Thanks for the post Mpt.

I've often wondered about retigabine as its 'in-the-neighborhood'.

Since global tinnitus numbers are immense it's a shame we don't by now have a rich databank of off-label tinnitus drugs success stories like yours, especially from chronic patients.

Looking to the bright side, if Potiga works for some, this gives us even more hope for AUT00063.

So if anyone else has tried this, please let us know, thanks.

 

[lapidus]

Reading up a bit on retigabine and it's potential for treating T. All the articles I find only states that it can treat acute T and prevent chronic T. Getting so tired of this talk about acute T, sigh...

 

[Johno]

Reading up a bit on retigabine and it's potential for treating T. All the articles I find only states that it can treat acute T and prevent chronic T. Getting so tired of this talk about acute T, sigh...

Acute T, chronic T, in my opinion same thing, if its cochlea damage induced. I personally dont believe in T memorization . Just unproven theory, nothing else.

 

[Grace]

Uproven theory until proven. Now if someone with chronic T got relief from it i would be happy and more excited for autifony.. But 5 monthes is still acute i guess :-/ .. Just the fact that theres nothing anywhere on retigabine that helped someone with chronic T... Besides anything any drug experimenting that has helped someone with chronic T. Im sick of this acute shit too and im actually starting to believe it and dont want to unless they prove it to me that theres no difference.

 

[Telis]

If there is NO difference between acute and chronic, like a lot of you think, why recruit acute to pad your stats in the initial testing? They are recruiting acute, correct?

Would this not make sense that there would HAVE to be a difference? If they can better the results with acute tinnitus, that tells me there is definitely a difference. This is just my common sense thinking....There are people on this board that are way more up to speed and educated in this matter than I. I could be way way off here!

I'm definitely not saying that this drug is not designed for both groups, but if there is ZERO difference, why even bother putting certain parameters into the testing?

I'm not trying to be a downer here, I want this as bad as anyone! Tell me if I'm out to lunch .....please!

 

[Grace]

If there is NO difference between acute and chronic, like a lot of you think, why recruit acute to pad your stats in the initial testing? They are recruiting acute, correct?

Would this not make sense that there would HAVE to be a difference? If they can better the results with acute tinnitus, that tells me there is definitely a difference. This is just my common sense thinking....There are people on this board that are way more up to speed and educated in this matter than I. I could be way way off here!

I'm definitely not saying that this drug is not designed for both groups, but if there is ZERO difference, why even bother putting certain parameters into the testing?

I'm not trying to be a downer here, I want this as bad as anyone! Tell me if I'm out to lunch .....please!

Yeah im startin to think that too. Sounds like theres definally a difference. And great acute will be the first T cured and forget all about the people that need a treatment first (chronic). Why are our brains so damn difficult. ---- although bill on here talked about his theory on chronic T. A little while back and it made sense to me anyways... Gave me hope at least.

 

[Johno]

If there is NO difference between acute and chronic, like a lot of you think, why recruit acute to pad your stats in the initial testing? They are recruiting acute, correct?

Would this not make sense that there would HAVE to be a difference? If they can better the results with acute tinnitus, that tells me there is definitely a difference. This is just my common sense thinking....There are people on this board that are way more up to speed and educated in this matter than I. I could be way way off here!

I'm definitely not saying that this drug is not designed for both groups, but if there is ZERO difference, why even bother putting certain parameters into the testing?

I'm not trying to be a downer here, I want this as bad as anyone! Tell me if I'm out to lunch .....please!

I dont know. Only wrote, that I dont believe in T memorization, because WHY? Always in nature had some reason, but T memorisation dont. I dont believe, than mammals body is so "stupid".
If excitotoxicity causes T, than :
http://www.sciencedirect.com/science/article/pii/030439409090454H

 

[Jordan4]

I'm three and a half weeks in.. what should I get and how?

 

[LondonGirl]

Imagine you are the CEO of Autifony, what do you want to achieve?
1. Funding, so you can carry on your work and proceed to various stages of clinical trials
Consequence: you 'big up' the potential of the drug - based on your research to date - and the scope of its effectiveness because you want potential investors to get excited and see £/$ signs. So acute/chronic, ageing-induced, noise-induced, oxytoxic drugs-induced, Autifony has presented genuine early evidence to potential investors illustrating that potentially it could help all of these scenarios.
Result: Autifony has secured comparatively high levels of initial funding for an exploratory, as yet untested (for efficacy on humans) drug.
2. Attain optimal early clinical trial results, so you can carry on your work and proceed to next stage trials, help more people (I'm assuming they are principled, decent folk here, which I am inclined to think is the case ) and achieve success for your reputation, company, shareholders and 'patients'.
Consequence: you set up the clinical trial conditions and entry criteria to maximise the likelihood of early positive results. So, possibly acute vs chronic tinnitus. If you can achieve early green lights, it makes it easier to garner buy-in (in every sense) to proceeding further.
Result: no-one knows yet, 'cos they haven't done it (except on rats induced with acute tinnitus)
CONCLUSION ON EFFECTIVENESSS OF AUTIFONY AND WHETHER IT WILL WORK ON ACUTE AND/OR CHRONIC TINNITUS: we will have to wait and see! That's why they're doing a trial. Anything else is conjecture at this stage. Ideally would be great if some people on here could get into the trial and report back.....
Peace to all

 

[111]

I will just add my view on this topic ( for what it is worth... ) I see no difference in chronic or acute in anyway. Something happens in the first place and triggers off a reaction ( for want of a better term ) that causes the noise to start, thats then it, the noise is the noise. Maybe they just assume people with early on set will see a faster change than people who have had had it for a while, which will mean more investors for them.
In case you are wondering what my situation is, well i have had this for 45 years... ( and i am still in my 40's ) so i think you could say i fit in the chronic category, and i have done things that just blow some theories on this thing out the window. If they are saying that it gets stuck in the brain then please explain to me why 2 years ago, after 43 years of having this, i had a medical condition, that when cleared suddenly saw me having complete silence for a while. I can tell you, as daft as this sounds, i found it quite frightening at night time, to hear total silence for probably the first time ever, i kept waking up and jumping up in bed and clicking my fingers, just to hear some noise...... strange really.. lets just keep things crossed that this tablet works for all of us.

 

[RichL]

yes and no-- i had my ears syringed and a few hours later while standing in my very loud shower (90db) a siren went off in my ear that I could hear over the shower- so I believe it was an interplay of the two

Sorry to get off topic but I think you better check the quality of your decibel reader, 90db for a shower?? that's equivalent to a truck or a jack hammer and doesn't sound right to me, that would be giving you hearing damage every time you showered!

 

[lapidus]

Uproven theory until proven. Now if someone with chronic T got relief from it i would be happy and more excited for autifony.. But 5 monthes is still acute i guess :-/ .. Just the fact that theres nothing anywhere on retigabine that helped someone with chronic T... Besides anything any drug experimenting that has helped someone with chronic T. Im sick of this acute shit too and im actually starting to believe it and dont want to unless they prove it to me that theres no difference.

Lidocaine has helped people with chronic T, but only temporarily for a couple of hours or so. But still, it's a proof that it can be treated medically. They just need to find out what, why and how.

 

[Grace]

True, true. Forgot about that, so then thats proof that its at least possible.. Its just sounds hard to figure out. And someone else said that lidocaine was a potassium channel drug also... So maybe autifony is thinkin there drug could do what lidocaine does for some but more safe and obviously results might last longer/forever if taken everyday.

Lidocaine has helped people with chronic T, but only temporarily for a couple of hours or so. But still, it's a proof that it can be treated medically. They just need to find out what, why and how.

 

[benryu]

True, true. Forgot about that, so then thats proof that its at least possible.. Its just sounds hard to figure out. And someone else said that lidocaine was a potassium channel drug also... So maybe autifony is thinkin there drug could do what lidocaine does for some but more safe and obviously results might last longer/forever if taken everyday.

Lidocaine is not exactly affecting the potassium channel itself, it's a sodium channel blocker (http://en.wikipedia.org/wiki/Sodium_channel_blocker).
The main link between potassium and sodium is that they both perform many of the same body functions, such as muscle contraction and fluid balance, however they usually do so in an opposing manner.

In our case sodium is affecting the potassium channels (in the bad way). Hence by decreasing sodium importance, lidocaine allow blindly ALL potassium to work more, this is also why it's not a cure itself as it doesn't target one specific potassium channel as the AUT00063 does.

 

[Zimichael]

FYI... To those picking up on the @Mpt and Retigabine connection here...It is a "double post" and also has it's own thread in the Treatments section.

[And yeah, moderators...I wouldn't know what's best either re joining these threads or leaving separate! As Retigabine is not Autifony maybe wise to keep leaving it as it is or it could get confusing].

Zimichael

 

[Grace]

Lidocaine is not exactly affecting the potassium channel itself, it's a sodium channel blocker (http://en.wikipedia.org/wiki/Sodium_channel_blocker).
The main link between potassium and sodium is that they both perform many of the same body functions, such as muscle contraction and fluid balance, however they usually do so in an opposing manner.

In our case sodium is affecting the potassium channels (in the bad way). Hence by decreasing sodium importance, lidocaine allow blindly ALL potassium to work more, this is also why it's not a cure itself as it doesn't target one specific potassium channel as the AUT00063 does.

so basically autifony could work better then lidocaine maybe since its gonna target one channel

 

[benryu]

so basically autifony could work better then lidocaine maybe since its gonna target one channel

Yes this is the idea, it's more specific, so more efficient and with less side effects. (coz trust me u don't want to be on lidocaine all day )

 

[Grace]

Yes this is the idea, it's more specific, so more efficient and with less side effects. (coz trust me u don't want to be on lidocaine all day )

Okay got it lol. And since lidocaine works on some chronics, then this should actually relieve most people im thinking. If anything probably like a bigass reduction. Ugh i was i could seeee intooo the futuree!!!!

 

[john2012]

Lidocaine is not exactly affecting the potassium channel itself, it's a sodium channel blocker (http://en.wikipedia.org/wiki/Sodium_channel_blocker).
The main link between potassium and sodium is that they both perform many of the same body functions, such as muscle contraction and fluid balance, however they usually do so in an opposing manner.

In our case sodium is affecting the potassium channels (in the bad way). Hence by decreasing sodium importance, lidocaine allow blindly ALL potassium to work more, this is also why it's not a cure itself as it doesn't target one specific potassium channel as the AUT00063 does.

thanks for this.
so Lidocaine seems to be a back-door poor man's Aut00063 at best, and even then it's pretty miraculous.
So Aut00063 will be much better (than miraculous!) by virtue of directly targetting the cause of tinnitus.

This is an interesting eye opener as to why so many different meds like ADs, anti-convulsants, anti-psychotics, beta blockers, etc can all work to alleviate (or cause/aggravate) tinnitus.

As Benryu elucidates, lidocaine work indirectly because of the intricate inter-relationship of brain chemicals. When you understand that lidocaine affects not only voltage-gated potassium channels but also blocks sodium and calcium as well(!), it gets misleading and you can understand why University of Leicester have hopefully done well to unravel this spider's web.

IF YOU'RE ALREADY BORED, STOP READING HERE! (thanks for reading this far)


The below info on potassium channels may be of interest and I've bolded a question:

KV3-type potassium channels have unique properties "...fast activation and fast deactivation that enable cerebellar neurons to generate brief action potentials at high frequencies"
http://www.ncbi.nlm.nih.gov/pubmed/19247732

De-activation of KV3 channels (identified as being designed for high frequency repetitive firing) maximizes the quick recovery of resting conditions...http://www.ncbi.nlm.nih.gov/pubmed/11506885)

Potassium channels may also be involved in maladaptive pain signalling
(note: chronic pain has been likened to tinnitus)
"Potassium (K⁺) channels are crucial determinants of neuronal activity throughout the nervous system. Opening of these channels facilitates a hyperpolarizing K⁺ efflux across the plasma membrane that counteracts inward ion conductance and therefore limits neuronal excitability."
http://www.ncbi.nlm.nih.gov/pubmed/24461875

The book 'Disorders of Central and Auditory Processing'
talks about KV7 potassium channels (Autifony's target) regulating auditory activity. Cool.
It then tells how both Maxipost and R-Maxipost completely suppressed salicylate-induced tinnitus.
Weird because they have opposite actions on KV7 channels.
The author concludes they might both instead act on BK (= big potassium) channels....whatever they are!!!?

Anyway, potassium channels have sub-units.
For example KV7 might consist of say KV7.1-KV7.5
So does anybody know if AUT00063 targets any particular sub-unit?


(http://books.google.co.uk/books?id=AT1YAQAAQBAJ&pg=PA351&lpg=PA351&dq=auditory kv7 channel&source=bl&ots=ujkFnAbmnZ&sig=ry0S2bMU_63SxewYvvehgwdtzUs&hl=en&sa=X&ei=sj3AU8WBOszmPMnRgaAP&ved=0CCoQ6AEwAg#v=onepage&q=auditory kv7 channel&f=false)

 

[Hudson]

thanks for this.
so Lidocaine seems to be a back-door poor man's Aut00063 at best, and even then it's pretty miraculous.
So Aut00063 will be much better (than miraculous!) by virtue of directly targetting the cause of tinnitus.

This is an interesting eye opener as to why so many different meds like ADs, anti-convulsants, anti-psychotics, beta blockers, etc can all work to alleviate (or cause/aggravate) tinnitus.

As Benryu elucidates, lidocaine work indirectly because of the intricate inter-relationship of brain chemicals. When you understand that lidocaine affects not only voltage-gated potassium channels but also blocks sodium and calcium as well(!), it gets misleading and you can understand why University of Leicester have hopefully done well to unravel this spider's web.

IF YOU'RE ALREADY BORED, STOP READING HERE! (thanks for reading this far)


The below info on potassium channels may be of interest and I've bolded a question:

KV3-type potassium channels have unique properties "...fast activation and fast deactivation that enable cerebellar neurons to generate brief action potentials at high frequencies"
http://www.ncbi.nlm.nih.gov/pubmed/19247732

De-activation of KV3 channels (identified as being designed for high frequency repetitive firing) maximizes the quick recovery of resting conditions...http://www.ncbi.nlm.nih.gov/pubmed/11506885)

Potassium channels may also be involved in maladaptive pain signalling
(note: chronic pain has been likened to tinnitus)
"Potassium (K⁺) channels are crucial determinants of neuronal activity throughout the nervous system. Opening of these channels facilitates a hyperpolarizing K⁺ efflux across the plasma membrane that counteracts inward ion conductance and therefore limits neuronal excitability."
http://www.ncbi.nlm.nih.gov/pubmed/24461875

The book 'Disorders of Central and Auditory Processing'
talks about KV7 potassium channels (Autifony's target) regulating auditory activity. Cool.
It then tells how both Maxipost and R-Maxipost completely suppressed salicylate-induced tinnitus.
Weird because they have opposite actions on KV7 channels.
The author concludes they might both instead act on BK (= big potassium) channels....whatever they are!!!?

Anyway, potassium channels have sub-units.
For example KV7 might consist of say KV7.1-KV7.5
So does anybody know if AUT00063 targets any particular sub-unit?


(http://books.google.co.uk/books?id=AT1YAQAAQBAJ&pg=PA351&lpg=PA351&dq=auditory kv7 channel&source=bl&ots=ujkFnAbmnZ&sig=ry0S2bMU_63SxewYvvehgwdtzUs&hl=en&sa=X&ei=sj3AU8WBOszmPMnRgaAP&ved=0CCoQ6AEwAg#v=onepage&q=auditory kv7 channel&f=false)

http://en.wikipedia.org/wiki/KCNC1

That one.

 

[jazz]

http://en.wikipedia.org/wiki/KCNC1

That one.

Thanks, Hudson!

 

[Christian78]

Lindocaine destroys neurons. It is toxic for nerves.

 

[john2012]

http://en.wikipedia.org/wiki/KCNC1

That one.

yeah, thanks Hudson

Hi Christian, lidocaine isnt an angel but illustrates something central worth targetting.

another thing, Too much lidocaine causes tinnitus. so will dosage be important to Autifony?

I really do hope we are close to a cure.
there's so many freakin sub-units i pray autifony can hit the right ones.
Dan assures me we can consider the rats chronic so take heart from that. thanks Dan.


sand and langguth's 2011 study adds weight to this area of research. a lot of it sounds klingon but you get the idea.
anyone who can translate gets a free latte. but don't sweat it, just curious.

"A complex interplay of multimeric potassium channel-forming proteins in auditory perception calls for follow-up examinations of interacting molecules that control the excitability of sensory neurons, including structures that are targeted by anti-tinnitus drugs. For lidocaine, these candidates comprise KCNA1 and KCNC1, plus KCNH2 [37,38], which has also been implicated in phenytoin effects [39]"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180252/