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

I live in Montreal too so let me know how that goes

 

So what happens in this next stage that should start in September?
How long before we know results of that stage?

 

they gonna cure some people.

 

Dan I hope your answer is correct

I'm interested in technicality of the next stage, not sure if anyone knows any details!

 

There isnt much details out yet except that they plan to start it in september/october this year. The only way we will know about what's going on during the phase is if someone from here gets into the trial and report back to us.

 

We need to send our Cat Marine Corps Force Reconnaissance !

 

Sooo funny!!
I thought you might have put a rats face in there ;-)

 

People seem to argue about whether acute or chronic tinnitus are the same. Well IMO this article explains their difference pretty well: nutritionreview org/2014/07/silencing-tinnitus-new-research-seeks-to-reduce-ringing-in-ears/

So if I understood correctly:

Acute tinnitus is the condition where damaged hair cells emit excess quantities of glutamate (amino acid which tells nerve cell to send "sound pulse") and because of this nerve cells, attached to haircells, die. This leaves nerve cells in switched-on state and the T in in da house. AM-101 tries to help healing process of nerve cells by limiting glutamines entry to nerve cells and kill em again.

On the other hand, chronic tinnitus is much deeper on the brain. So even if your hair- and nerve cells in ear are recovered, the T is still in deep in the brain (Protein encoded by KCNC1 gene with kv3 channels etc and KCNQx genes etc). Anyway, "deep brain nerve cell overfiring" is trying to be cured with AUT00063


If I have understood correctly:
1) to cure acute tinnitus you need AM-101,
2) to cure subacute tinnitus, you would need AM-101 and AUT00063
3) To cure chronic tinnitus you need AUT00063. As additional speculation - maybe both are needed if the nerve cells in the ear aren't ok yet?

 

1/ Yes and most likely relapse for chronic T.
AUT00063 may be still needed in a lot of cases.

2/ Yes AM-101 to a certain extent as we are not sure about the time frame, AUT00063 for sure.

3/ Yes AUT0006, but the cure should not be dependent of the nerve cells.
(hair cells in the inner ear are related to the audition quality and trigger the T., but are not necessary for a cure. Work are done around this area to help reparation of the cells, but we still have a long road to get there)

 

Hi, yes, hair cell initially trigger the T by emitting too much glutamate. But the damaged nerve cells (because of excess glutamate) are the ones which leave the gate open and in some time - train the auditory cortex to be hyperactive from some parts (frequencies)?

 

Yes glutamate is being released, AM-101 is nothing more than a glutamate blocker that prevent glutamate from locking potassium channels but it does not damage nerve cells. It was believed back in 2004 (Eggermont JJ, Roberts LE. The neuroscience of tinnitus.) but it was a supposition and was took as granted in other papers. However it was contradicted in recent papers. (including one coming from the AUT00063 )

 

If AUT00063 shows good efficacy, I bet it will be fast tracked through the approval process. There's a high number vets getting disability for tinnitus which is costing the government potentially into the billions. If the results are good, I bet this drug will be available in 4-5 years at the longest.

 

Yeah as discussed above in the thread depending on their strategy / efficiency some of us could benefit from the drug in 1,5 year and the common joes would not have to wait more than 3-4 years, 5 years in the very worst case scenario.

 

Is it safe to say that now they know for sure what is the couse of tinnitus?

 

i think am-101 will be a first line treatment that will literally be effective mostly in the first week of tinnitus- the study results for phase two are in my physician father in law's words .... "pitiful", they basically tortured the data and kept narrowing patient groups to show some efficacy, and the result was a small sample size --those results still weren't great for by any measures in relation to the placebo group

 

Ok, this was new info for me. Thanks for the update. You happen to have source doc for this info that glutamate does not damage nerve cells in ear?

 

@lapidus

Autifony has two patent applications for treating a variety of hearing and psychological disorders based on KV3 inhibitors. One patent is for Hydantoin derivatives as Kv3 inhibitors, and the other is for Triazoles as KV3 inhibitors. In both patent applications, they mention the Kv3.1 channel as giving rise to a hyperacusis. Specifically, they refer to hyperacusis associated with Fragile X syndrome and autism. Since hyperacusis and tinnitus drugs will be targeting the same channels, it is likely that all types of hyperacusis will be treatable.



Of note, Autifony is only working with Kv3.1, KV3.2, and KV3.3. But these three channels have wide ranging applications in neurological diseases. In reading both patents, it sounds like Autifony is out to revolutionize neurology.

This is from their Hydantoin derivatives patent application:



Equally important, Autifony hypothesizes that KV3.1 and/or KV3.3 should be useful in preventing hearing loss (including from noise exposure) and KV3.1 and/or KV3.2 should be useful in preventing tinnitus.

References:

http://www.google.com/patents/WO2012168710A1?cl=en

http://www.google.com/patents/WO2013175215A1?cl=en​

 

Thanks @jazz ! You're the best

I've read that patent a while back when Dan (I think) posted it but couldnt really understand what this fragile-x thing was. I do wonder though if H is in the brain like T or if it is some malfunction in the middle ear that is causing it. In that case Autifony wouldnt be useful? But what you just said do indeed sound promising to say the least.

 

Quickly everyone! Throw money at them!

 

@benryu , I too would like to know the source doc....

 

I shared all sources with locoyeti, but did not have time to order it up, feel free to PM @locoyeti or me if you need it <3

 

I must confess, I have not really kept myself up-to-date with this thread, but I had an e-mail exchange with Mr. Large (CEO Autifony) today, and he confirms that the clinical trial of AUT00063 will continue in September/October. He also mentioned that there will be enrollment information made available on their own website in September (possibly slightly earlier). The clinical trial is UK based.

I was not able to gain any additional information about the trial and/or potassium modulators such as Trobalt/Flupirtine.

Some might ask why I haven't simply copied the entire e-mail into this thread. The reason is quite simple: despite the somewhat "rehearsed" reply from Mr. Large - I owe him the respect to not "publicize" a personal e-mail. This is the reason.

 

Do you know what the eligibility criteria will be?
T less than 6 months?
No having taken part in AM101 in less than x months or at all?

 

No, he didn't mention. But then again, I didn't ask.

I would have called him instead yesterday, but I needed his answer in writing (as I was seeing my GP later on for other reasons; see Flupirtine thread). I prefer to speak with the medical companies as they tend to reveal more information when having a spoken, rather than written conversation. Mr. Large clearly is someone who will only give a very standard, minimalistic, and rehearsed reply. And for good reason - it could all end up an Internet forum such as... this one! So, I don't blame him, at all - really. And he did answer personally and within two hours...

So give him a call. As an example, it is only two weeks ago that I had a 30 minute phone call with the medical director of the first stem cell clinic I was treated at in Bangkok, followed by another 30 minute phone call with the resource organization that helped me locate it (in the first place, last year). Because I had this phone call, I learnt that there is a new potentially promising treatment protocol for hearing loss (using stem cells). I have not put this information into the research section of this forum because it is not public information yet - and I am also waiting for the treatment company to announce it on their website. And... I am also a little bit skeptical - I hate to announce news that turn out to be... not so promising. But I will supply @Markku with a copy of the material so as to prove that this is real (just as I do with all the other things I post). But, the main point here is: make a habit of speaking with the people who are at-the-edge-of-science. That's how you learn...

 

I had a meeting with a very good ENT doctor yesterday. He will be involved in the Autifony trials and looked up the eligibility criteria for me. This is only from the draft protocol (so not finalised; needs approval from ethics committee etc.) and is also not complete - mainly as relevant to myself (I am not eligible).

- Time since onset is up to 18 months although the wording was a little vague and seemed to say that they would prefer people up to 12 months initially. But up to 18 months is technically eligible as I understood the passage he showed me.

- Your hearing loss will be measured over several specified frequencies. I cannot remember exactly which they were but they started at 250Hz. Your AVERAGE hearing loss over those frequencies needs to be greater than 20db and less than 60db in order for you to be eligible.

The second point seemed to me quite a stringent criteria. I have almost no hearing loss at lower frequencies such as 250Hz. To want >20db averaged out over the range I would guess they are looking for people with a fairly profound hearing impairment as well as tinnitus. Off the top of my head, I do not understand the rationale behind this criteria.

As I said, these criteria are not finalised nor are they likely to be the only criteria.

 

Yes it seems very strange. They will never find enough people who fits into that very specific criteria.

 

Another thing I found out (not sure if this is covered elsewhere in the thread) is that the trial is for a one month course of medication. Now, I'm not sure whether this means that they believe that using the drug for one month will result in a long term benefit, or whether they only intend to test it over a one month period but the drug is intended to be used for the rest of one's life once licensed. I asked the ENT about this and he kind of laughed and said something along the lines of "Well, of course drug companies want you to be on their drugs for life." But when I pressed him further he conceded that he did not know.

 

Sound like they will go for a phase 2 in several sub phases.
The 12 up to 18 months makes total sense
I don't necessarily understand the reason for criteria on the frequency.

Let's wait for a public release, they might refine it a lot.

 

I would say that the frequency range they're is between 250 hz- 8000 hz (8 Khz).
As far as I know that's what the standard test in pure tones is for audiology in the states.

 

I think it might be easier to judge improvement on the lower freq range cause they are bit more resistant to damage - I would think in the average tinnitus sufferer still has their hearing under 8000 hz. like me. ?