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

Autifony has been flying under the radar for a while, with a pretty basic website. They recently posted what looked to be pretty good results from an animal study of theirs at the TRI.

They supposedly have a drug in Phase 1 trials for the treatment of tinnitus, at least according to their website. I haven't seen anything on clinicaltrials.gov though. It's worth a look at their website though.

http://www.autifony.com/autifony-pipeline.asp

Oh, and the study I am referencing is the "Turner J: AUT3, a Kv3 positive modulator, suppresses chronic noise induced tinnitus in a rat model" study in the TRI 2013 abstract.

It will be interesting to see how this goes, although Phase I trials are pretty early clinical trials. Here's to the next compound! One has to work eventually

 

I guess some people on this forum wish they were rats

Looks promising anyway !

 

"Research shows that tinnitus usually arises within the central nervous system, and may be caused by increased neural activity in regions of central auditory pathway. Thus treatments for tinnitus need to focus targets within the brain, and not the cochlea."

That is whole point, when world medicine finaly recognize that, T could be resolved....until that talking with old knowledge ENTs is wasting a time...

 

After contacting them, they have responded and told me that the Phase 1 trial is strictly for safety studies. They are only enrolling healthy volunteers with no tinnitus or measureable hearing loss.

 

London, UK, - 4 June 2013 -
Autifony Therapeutics Limited ("Autifony"), which is pioneering the development of novel pharmaceutical treatments for hearing disorders, today announced the start of a Phase I clinical study of the novel, first-in-class Kv3 potassium channel modulator, AUT00063.
This is a randomized, placebo controlled Phase I study, conducted in the UK, to investigate the safety, tolerability and pharmacokinetics of orally administered single and multiple dose regimens of AUT00063 in around 60 young and elderly volunteers. The study, which is also exploring a variety of novel pharmacodynamic endpoints and interactions, is expected to be completed in Q1 2014.
AUT00063 is being developed as a treatment for age-related hearing loss and tinnitus. Despite the fact that 50% of those aged over 60 suffer from age-related hearing loss and 10% of the population suffer from some form of tinnitus, there are currently no effective treatments for either condition. AUT00063 is a novel pharmaceutical that targets auditory processing in the brain. Deficits in these central mechanisms are believed to contribute to hearing difficulties in the elderly as well as the emergence of tinnitus.
Read more:
http://www.autifony.com/publications/Autifony_AUT00063_FIH_Start__Fundraising_FINAL_03Jun2013.pdf
I have contacted them and they are only accepting healthy volunteers as this is a safety study. Hopefully they will expand and allow some chronic tinnitus sufferers in on further trials!
I would also like to add that this treatment is going to target "chronic" tinnitus as opposed to the acute phase tinnitus targeted by the AM-101 compound.

 

I don't think it's a question of if or when anymore, but who will get to a treatment first.

 

Oh guys I hope this works too. I'm going through a spike at the moment and its not fun. I was thinking today in 10 years time I'll only be 40 and the thought of having to listen to this noise forever scares me. Come on the UK I hope this is successful

 

I'd live a life of impotence for a life of silence.

 

I would gladly trade tinnitus for impotence.

 

I would take the impotence and then find a way around it like the champ I am.

 

Since somebody asked about this pre-clinical rat trial, I am bumping this thread.
I call it the miracle tinnitus rat study.

http://www.autifonytherapeutics.com/publications/Turneretal2013-TRI_final.pdf

 

Just as a reminder to people, as I was confused about what every trial is about:
FAQ
ClinicalTrials.gov - Clinical Trial Phases
Question: What are clinical trial phases? Answer:
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

• Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
• Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
• Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
• Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

 

Note:
Phase II studies are sometimes divided into Phase IIA and Phase IIB.

• Phase IIA is specifically designed to assess dosing requirements (how much drug should be given).
• Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)).

Some trials combine Phase I and Phase II, and test both efficacy and toxicity.

 

That is amazing! Stuff like this really gives me hope.

 

OMG, yes! Hope!

 

More Autifony talk:
Pharmatching.com

What do age-related hearing loss and schizophrenia have in common? Not much, on the face of it. However there is growing evidence that the two disorders may have a link through the dysfunction of certain ion channels in the central nervous system. Ion channels are membrane proteins that help convert chemical or mechanical messages into electrical signals in the cell.
Autifony Therapeutics Ltd, a spin-out of GlaxoSmithKline Plc, is actively exploiting this research space. Specifically, it is looking to develop new small molecule compounds that modulate the Kv3 potassium channel in the brain and thereby treat patients who either have an age-related hearing loss and tinnitus, or schizophrenia.
On 1 July, Autifony and researchers at the University of Manchester and Newcastle University received a £1.9 million grant from the UK Technology Strategy Board to develop a Kv3 potassium channel modulator for schizophrenia. The collaboration has total funding of £2.75 million. It will enable researches to select a compound from a group of potential candidates and take the molecule through preclinical development to a first clinical trial.
This comes just a month after Autifony started a Phase 1 study in healthy volunteers of another compound that targets the same ion channel – but for the age-related hearing loss and tinnitus indications.
In an interview, Charles Large, Autifony’s chief scientific officer, said that it “may sound a little curious” that hearing loss and schizophrenia could be related. But the ion channels that the company is targeting in its hearing loss programme are closely implicated in brain circuits that are believed to be dysfunctional in schizophrenia.
Schizophrenia was, in fact, one of the diseases GSK researchers were investigating at the company’s neuroscience drug discovery unit in Verona, Italy when management decided to shut down the centre in 2010. At the time, Dr Large and Giuseppe Alvaro were both centre directors. In subsequent negotiations with GSK, the executives acquired several pre-candidate, voltage-gated ion channel modulators and associated patent applications.
In the year up to the founding of Autifony in 2011, they started to study the compounds in hearing – leaving the schizophrenia indication aside for the time being. “The hearing story was something that we developed almost exclusively subsequent to the closure of the neuroscience division. It was something that we felt would be an important basis for the new company,” Dr Large commented.
The hearing loss and tinnitus indications have in fact been the main focus of the company since that time. “It is fairly clear if you look at the statistics that despite the very large number of people who suffer from hearing loss as they age, very few end up successfully using a hearing aid. One of the reasons for this is that hearing aids don’t really address one of the key problems, which is the ability to understand speech in a noisy environment,” Dr Large said.
This inability to understand speech is thought to be linked with a dysfunction of the ion channels that process sensory information in the brain. By modulating Kv3 potassium channels in the auditory brainstem, the company hopes to correct these signalling problems.
Autifony announced the start of the Phase 1 study in hearing loss on 4 June. The study is expected to complete in the first quarter of 2014 after which the company plans to bring it into patients. If the compound is successful and is marketed, it could be used in combination with a hearing aid – depending on the nature of the patient’s disorder, the executive said.
Since its founding in 2011, Autifony has raised £15.75 million, which includes a £5 million investment from Pfizer Venture Investments, announced on 4 June at the time of the Phase 1 trial start. Initially, GSK took a minority stake in connection with the start-up. This stake has since been diluted and the company’s three largest shareholders are now SV Life Sciences, Imperial Innovations Plc and Pfizer Venture Investments.
UCL Business Plc also has a small stake in connection with Autifony’s work with University College London’s Ear Institute on the hearing disorder project.
Meanwhile, the Technology Strategy Board grant will enable the company to carry out early schizophrenia work, without taking resources away from the hearing loss programme.
MedNous interviewed Charles Large on 28 June 2013.
Copyright 2013 Evernow Publishing Ltd

 

Umm. A summary please?

 

I'm really excited about the results so far. I just hope the trials show it's save and effective.

 

That was the summary

 

uhm sounds similar to Effects of the potassium ion channel modulators BMS-204352 Maxipost and its R-enantiomer on salicylate-induced tinnitus in rats. If anything because it mentions KvSomething channels that I couldn't tell you what they are for the life of me.

 

"Our original hypothesis was that Kv7.2-Kv7.5 channels might play a key role in tinnitus generation and that Maxipost but not R-Maxipost would suppress tinnitus; however, it appears that a shared mechanism between Maxipost and R-xMaxipost, such as inhibition of Kv7.1 channels or activation of BK channels or some novel mechanism common to both compounds, underlies salicylate induced tinnitus as both compounds completely abolished behavioral evidence of tinnitus in a dose-dependent manner."

For the life of me, I don't know what is taking them so long!

 

what is sylacatyle tinnitus?

 

Sorry I was drunk, and on mobile with very cold hands.

Yes.

So I guess this doesn't have any potential for noise induced T?

 

I'm pretty sure AM-101 is specifically made for noise-induced T. The idea is that neurons get over-activated in your ear and after doing it so many times they have a harder time resetting themselves. I remember being younger and my hearing threshold being completely fucked after a club (couldn't hear anyone outside) but absolutely no ringing. It went away within about 30 minutes. The last show I went to without substantial hearing protection (shitty foam plugs), my ears were actually completely non-ringing for 30 minutes after the concert, because my brain was so used to the hearing threshold I had made it accustomed to. Next morning, my ears were crazy pulsating and shit. The pulsating has mostly gone away, and I've even had days where my high frequency T has been gone, only left with the low hum I've had for most of my life.

The point of that rant is to say that your ears have a harder time recovering the older you get and the more times you expose yourself to high thresholds of sound. The idea of AM-101 is to reset the part of your ears that cannot seem to reset themselves. The brain hasn't "learned" the sound by any means and that's been disputed several times over. The sound comes specifically from a dysfunction in your auditory system, most likely the neurons over-firing. VNS and AM-101 are both very likely going to be able to silence T for many of us, a small percentage will unfortunately remain unchanged because other mechanisms in their brain are causing dysfunction of the auditory system. If yours was caused by noise it would make sense that you're most likely going to benefit from one of these treatments.

Erlend, I've seen a few of your posts, it seems you haven't had T for that long yet (I know it seems long but it isn't, I just came up on my first year with invasive T). You still have a lot of time to recover and here's the best advice I can give you: get off the forums. Stop checking for a cure. Stop masking your tinnitus. Learn to accept it as a necessary hindrance and go on with your life. Stop talking about it, do your best not to bring it up in conversation with friends/family. It sucks, I know, and if you really need someone to talk to about it get a therapist who can help you get your life back in order. Get back to your hobbies, your work, whatever it is you need to do to be human. Remember your place in the world. Loads of celebrities, musicians and businessmen/women have tinnitus and don't let it slow them down. Mind over matter, my friend!

 

Thank you mintblue, maybe you're right...

But there's a part of me thinking that if I keep masking it until AM101 is available, the tinnitus won't reach my brain or whatever the reason post-acute sufferers can't get any benefit from it is..

 

Erlend, I read somewhere were they found that during masking, the brainwaves are different than when you listen to your tinnitus. Don't know the significance of that.

 

Erlend, masking does nothing but delay your habituation process. Habituation isn't just learning to tune it out, it's teaching your brain that the sound is unimportant and to stop concentrating on it. If you spent the next week focusing on your foot you'd find it to be a lot more sensitive than it currently is. The same goes for your tinnitus. I found that mine got enormously better when I stopped trying to mask/cure/fix it and just accept it as there. The sound literally decreased. Have you seen an ENT? Have you had your hearing checked?

 

Yes I have, perfect audiogram and nothing wrong with my ears.

Dno how high they went in the hearing test thohh