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

#243
rtwombly said:
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.
Click to expand...
Why do you feel that way?
 
#244
rtwombly said:
@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.



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.
Click to expand...

Oh please God i hope you are right LORD HAVE MERCY GOD i hope you are right.
I'll taking hearing loss any day over tinnitus.
 
#245
rtwombly said:
@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.
Click to expand...
man i really hope so at least a good treatment to keep the noise down until a cure is found and if they do test it and it removes tinnitus all together there looking at some big bucks $$$$$$$ and they will help millions of people live there life the fullest
 
#246
Dear friends,

I wonder can you give me link about where is states autifony's conditions for phase 2. And I wonder are we going to collect signatures for approving medication faster?
 
#248
Christian78 said:
Dear friends,

I wonder can you give me link about where is states autifony's conditions for phase 2. And I wonder are we going to collect signatures for approving medication faster?
Click to expand...
Look back in the thread, its there.
Its a little premature for signatures at this point, lets wait for phase2 results.
 
#249
rtwombly said:
from everything I've read, high pitched tinnitus is the norm. I am an exception, with a droning hum just a bit above 1000Hz.
Click to expand...
Maybe not the case .... Here is a reply from Peter Harris re my questions on broad spectrum hearing loss, getting on the trial if you are doing other trials (eg: am101) and/or other hearing studies(eg: neuro-modulation, trt or a drug that is targeting hearing loss, pill or otherwise):

Hi,

please watch the Autifony website over the next 4-6 weeks and you will see notice of sites opening for recruiting subject onto study, along with the contact number for each site. While we agree that most typical sufferers will have more losses at high frequencies, a majority will have some losses across the mid ranges too. Best check when the site nearest to you becomes active. We shall keep our eyes on the screening and why people might NOT get onto study.

Yes - to your question of taking other research drugs - must leave a 30 day gap before our study.

No - to your quesiton on previous hearing study - does not mean audiometry; it means either taking a drug, or having a drug injected (e.g. through the ear drum), or using some specialised equipment (e.g hearing aid) specifically being tested to affect the hearing process i.e to improve hearing or reduce tinnitus; i.e. a clinical study conducted on hearing. This exclusion is because there might be so-called carry-over effects that could interfere with our own study.

Best of luck and hope you're eligible when the study opens near you.

Peter Harris
CMO
Autifony Therapeutics
London

Of specific interest:
"...a majority will have some losses across the mid ranges too" - so you are the norm :) I am hoping that you don't have to have hearing loss at all frequency touch points. SO for you, maybe your one at 1000Hz makes you eligible. I will find out more.

"We shall keep our eyes on the screening and why people might NOT get onto study." - hopeful. It looks like they will be monitoring and (hopefully) adjusting criteria if too many people are being exempted on the current eligibility criteria. This confirms your reply from him.

"please watch the Autifony website over the next 4-6 weeks" - so still a bit of a wait before people can call and try get on.
 
#250
@dan my speculation is just because there doesn't seem to be a direct connection between Autifony's lead doctors and hearing loss research, unless that's something I've missed. Why motivated Dr Alvaro to found the company? Why choose Dr Large as CEO? I'm taking into consideration that the name, "Autifony", clearly has something to do with hearing, so they didn't just start out as a general research group. These are doctors who could be pursuing the cure for cancer, or Ebola, or working with stem cells to cure Parkinson's. Something tipped them off that using potassium channel modulators against tinnitus and hearing loss was enough of a good bet to make it their careers for the next several years.

@bedouin My hearing loss is 30ish Db below 1000Hz, and a right-ear notch at 4000Hz. So I do qualify in every way except for my citizenship. There ought to be an exception for Americans who can name all 13 Doctors, 15 if you count Peter Cushing and Richard Hurndall!
 
#251
rtwombly said:
@dan my speculation is just because there doesn't seem to be a direct connection between Autifony's lead doctors and hearing loss research, unless that's something I've missed. Why motivated Dr Alvaro to found the company? Why choose Dr Large as CEO? I'm taking into consideration that the name, "Autifony", clearly has something to do with hearing, so they didn't just start out as a general research group. These are doctors who could be pursuing the cure for cancer, or Ebola, or working with stem cells to cure Parkinson's. Something tipped them off that using potassium channel modulators against tinnitus and hearing loss was enough of a good bet to make it their careers for the next several years.

@bedouin My hearing loss is 30ish Db below 1000Hz, and a right-ear notch at 4000Hz. So I do qualify in every way except for my citizenship. There ought to be an exception for Americans who can name all 13 Doctors, 15 if you count Peter Cushing and Richard Hurndall!
Click to expand...
We should see the trial soon enough in usa. Hopefully it works like we're all hoping and praying.
 
#252
DebInAustralia said:
what is the mechanism of action of a KV3 potassium channel modulator?

does anyone know?
Click to expand...

Deb...There is a wealth of info. and speculation on this both back in this thread and the Retigabine thread. However, from my own perusal and time spent looking, there is a helluva lot more on say the Kv7 channels (Retigabine), than there is on the Kv3 channels (AUT00063). Pity, but there it is.

If you (and maybe others) want the best summary explanation I have found to date, of how the Kv channels supposedly work (and I would assume it is the same for Kv3, but just different "gates" on the neuronal cell), here is a post from the Retigabine thread.
Mmmmmm...I'm not sure if I can do a "quote carry-over" or if it will mess up??? Yeah can't seem to do it. So sorry, will have to do normal cut-and-paste so it is going to chew up some space below....

Best, Zimichael

-------------------------------------------------------------------------------------------------------------------

Wow, @@locoyeti ref. this… http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2011.03365.x/full

Great find on KCNQ's (Retigabine) action albeit for epilepsy study. All kinds of stuff in there, even GABA aspects, etc., etc. The summaries of action are the clearest I have seen so far I think!

For those following, or trying to follow the "mechanics" of this neuronal stuff, here is a key take from this article on the Kv7 channels that Retigabine acts on, and some hopefully accurate 'translation notes' of my own afterwards…

At the receptor, cellular and network level, the importance of KCNQ channels as key regulators of neuronal excitability is clear: they are able to work as a powerful inhibitory force in the brain by providing a continual hyperpolarizing influence to maintain or control the cell RMP and reduce subthreshold excitability. This key function provides a clear underlying explanation for the MoA of RTG/EZG that stabilizes KCNQ2–5 channels in the open position, increasing the recruitment of such channels at rest, and particularly following depolarization, that act to exert a hyperpolarizing effect on the cell. RTG/EZG therefore effectively primes the cell to resist firing bursts of action potentials that occur during the sustained depolarizations associated with the initiation and generalization of seizures.

OK, my simplified translation:

After 'action potential' (= let's do this!) is reached a neuron 'fires' and the subsequent electrical charge inside 'hyperpolarizes' = kinda goes too far. This puts a temporary damper on the speed with which the cell can return to the normal resting condition and fire again. Sort of like overshooting a turn in your car and you have do a U-turn, go back a bit, then get going again…in nano-seconds of course! The longer this 'hyperpolarization' lasts the harder it is for the cell to get back to normal (RMP = resting membrane potential) and fire again. Obviously, this then reduces "excitability" and the neuron's ability to just fire away like a machine gun. The thing got a bit jammed, so to speak.

The working hypothesis for this is that the drug action on KCNQ2-5 (Kv7.2-5) gates/channels does these things:

1. Stabilizes these channels in the open position = allowing more K+ ions to flow through the cell membrane and do their thing.

2. Increase the recruitment of such channels at rest = gets more of these particular doors/gates/channels ready to open when the cell is at rest (= 'normally polarized'). So basically telling these gate to stop being lazy and get the hell ready to "go"!

3. …and particularly following depolarization = re that above, making sure these gates don't just get a grip and open fast but also don't just goof off after doing so and get immediately lazy again. They have orders to stay active and open to allow for that hyperpolarization to take place through increased K+ flow and delay the "repolarization" of the cell back to normal resting state (which would then allow the ability to re-fire, etc., etc.).

4. RTG/EZG (Retigabine/Ezogabine = Trobalt/Potiga) therefore effectively primes the cell to resist firing bursts of action potentials that occur during the sustained depolarizations…So, the drug basically puts sand in the gears that allow the neuronal cell to just keep firing away like that machine gun = those "sustained depolarizations"! (Depolarization is the term for where the change in cell charge is enough to, generally speaking, trigger it to fire).

Incidentally, MoA = mechanism of action....I hope this helps. And I hope I got it right!

Best, Zimichael
 
#253
rtwombly said:
@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.
Click to expand...

rt...really nice explanation there. Thank you. Makes a lot of sense now v. not making much sense to me before!

Hopefully we can get more detailed info from inside the trial itself in due course once it starts. The key being HOPEFULLY SOMEONE ON THE TT FORUM HERE GETS IN!!! Thus a member that fits all those pretty (IMHO) restrictive entry requirements.

I guess we will just have to wait and say "The best of British" to whoever applies.

Zimichael
 
#254
To: Peter Harris, Chief Medical Officer Autifony

Thank you for your responses.
I hope you find the cure for this horrible condition. How many more people have to suffer or die.
Yesterday a member of my tinnitus support forum, Craig Muller, commited suicide after 2 years of suffering.
He was from the USA - 53 years old, a wife and 2 kids. He isn't the first and certainly not the last of people taking their lives because of severe tinnitus. I am sure the UK has its own fair share of tinnitus suicides.

On our tinnitus forum, we have been experimenting with a new drug on the market called Retigabine (an epilepsy drug).
It has a similar mechanism of action to Aut063 as it acts as a potassium channel opener, except that Retigabine acts on Kv7 channels as opposed to Kv3, so it is probably much less target specific for tinnitus - yet it is still effective to some degree. So far out of 8 people who are on it for a few weeks now, 5 have significant improvement, 1 person was cured, and 2 have no change.
We are asking our doctors to prescribe us this drug off label, it is very hard to get a prescription for this drug. As you can see, we tinnitus sufferers need our own medicine. Craig begged his doctor to prescribe this medication, but was refused. This is an unacceptable situation for us tinnitus sufferers.
I know that you at Autifony are aware of this tinnitus crisis and are trying your best to come up with a treatment - at least something to reduce the burden of suffering for those who have it bad, our lives destroyed, our families devastated.
It is possible to live with some degree of tinnitus, but when it gets to absurd volume levels, something must be done, its just inhumane. No human being should suffer like this.

I thank you deeply once again for your patience and attention.

If there is any way I can help or advise Autifony on behalf of tinnitus sufferers, I would gladly offer my time.
I know first hand what its like and I am a part of a very large online community of sufferers.

Response:
How awful for Craig and his family. You are right - so much misery and distress caused by this condition.
Thank you for the information on retigabine. Observations such as these can be highly informative and may eventually lead to a proper evaluation in the form of a randomised controlled study.

And many thanks for your offer of help and support. Right now our priority is to get the trial underway and get subjects onto study. But to your point, I would really value hearing non-confidential information on medications that tinnitus sufferers might use from time to time and whether they seem to benefit. You are right, Kv7 will not be expected to give the benefit of channel modulation more specific to the hearing pathways including Kv3,, but who knows with the CNS! We'll do our best to move things forward.


Kind regards.

Peter

Dr Peter Harris

CMO

Autifony Therapeutics

London
 
#255
Thanks @dan
Maybe you can direct them to Tinnitus Talk, especially the Retigabine user thread.
Just a note that they had mentioned (see earlier on in the thread), that they may open up to no hearing loss or different levels in later phases.
So let's not just connect it to specific hearing loss. This drug is intended for t.
Also, someone somewhere on TT please get onto this trial and keep us informed!!!
Cheers!
 
#256
@dan Thanks for sharing that. I'm not saying I won't try the Retigabine route again eventually, but Dr Harris's comment at least makes Autifony even more attractive as an options, since it might well clear up some of my hearing issues as well.

You can clearly see that Dr Harris at least is a caring individual and interested in helping people. If AUT-00063 winds up being the ace in the hole we hope it to be, maybe I'll save up for a UK trip just to shake the Autifony folks by the hand!
 
#258
#259
rtwombly said:
You can clearly see that Dr Harris at least is a caring individual and interested in helping people. If AUT-00063 winds up being the ace in the hole we hope it to be, maybe I'll save up for a UK trip just to shake the Autifony folks by the hand!
Click to expand...
Yeah , its nice to see that a pharma company actually cares about the people they are targeting.
 
#260
Can't see anywhere that people can't travel in from abroad for the trials. As long as they are around for the duration. Or am I missing something?
 
#261
Lisa88 said:
Can't see anywhere that people can't travel in from abroad for the trials. As long as they are around for the duration. Or am I missing something?
Click to expand...
@Lisa88 i asked and this was the response:


Thank you for your query. I apologise for sounding disappointing but we are not planning to enrol non UK participants into this, the first of our studies. Subjects would need to be UK residents with eligibility for UK NHS healthcare services, including those of their own GP, for safety monitoring and so on. I can advise that this is an early "proof of concept study" and that one or more larger studies would likely follow a positive finding, and any larger study will likely be multinational.

Yes, separately we certainly are talking with US experts as well as FDA about a US based study. Initially we shall be looking there at hearing loss associated with age but we also recognise the importance that the US governmental agencies put on the management of tinnitus, particularly in the VA field. In fact I am scheduled to meet with two of the largest VA facilities in October and November this year.

Sorry not to be able to respond more positively but I trust that you will understand matters.

Kind regards.

Peter Harris

CMO
Autifony Therapeutics
London
 
#262
Rube said:
@Lisa88 i asked and this was the response:


Thank you for your query. I apologise for sounding disappointing but we are not planning to enrol non UK participants into this, the first of our studies. Subjects would need to be UK residents with eligibility for UK NHS healthcare services, including those of their own GP, for safety monitoring and so on. I can advise that this is an early "proof of concept study" and that one or more larger studies would likely follow a positive finding, and any larger study will likely be multinational.

Yes, separately we certainly are talking with US experts as well as FDA about a US based study. Initially we shall be looking there at hearing loss associated with age but we also recognise the importance that the US governmental agencies put on the management of tinnitus, particularly in the VA field. In fact I am scheduled to meet with two of the largest VA facilities in October and November this year.

Sorry not to be able to respond more positively but I trust that you will understand matters.

Kind regards.

Peter Harris

CMO
Autifony Therapeutics
London
Click to expand...

Those brits are always ruining a good time I tell you! :)

Only kidding of course, I wish the best for all those involved in this study.
 
#264
He sounds like a jolly decent chap (as we Brits say!) and I think Autifony's motivation and values are honourable without being naive, and with a realistic appreciation of the necessary commerciality of bringing their developments to market.
 
#267
Maybe is a good idea to contact people on the British Tinnitus Asociation and see if it's posible to contact someone who signs for phase 2.
http://www.tinnitus.org.uk/ unfortunately there are really few messages in the forum, maybe should contact the Association and tell them the importance of this study and see what can they do to keep us updated?
 
#268
Ok I just have written a new thread in the British forum, let see if some one say something:

Hello, in October starts the trial phase 2 of the med AUT00063 from Autifony, That is briefly the BIGGEST hope for Tinnitus sufferers. From tinnitustalk forum we are willing to stay updated about this study but none of us is able to sign up as we dont meet the requirements. The study is made only for UK residents so thats why I'm posting here. If someone is signing or has some information, please share with us. Thanks in advance

Here is it: http://www.tinnitus.org.uk/topics/2584
 
#269
@dan
Thank you for writing that letter, I hope you didn't stop with Autifony.
I'm sure Craig would be proud of you to spread the word of his tragic experience to possibly bring relief to others and rise more awareness.
Response from AUT is encouraging, it's good to know that some people recognise the devastating effects of this horrible condition.
 

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