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

phase 1 is only about safety. in the article above, they state that they give the medicine to "healthy" people, so they don't have tinnitus nor hearing loss

 

Go for it! And report back to us!

 

Dear Nils,


Thanks for your interest in our programme. We have completed the phase I trial, and we will release the headline results via our website once the analysis is complete. However, I can say that we are planning to progress AUT00063 into phase II trials. An announcement on this will be posted on our website in due course.

We are in contact with Action on Hearing Loss and the British Tinnitus Association, and will ensure that they receive all relevant information regarding our trials as they emerge.

All the best,
Charles


Charles Large, PhD.
Chief Scientific Officer
Autifony Therapeutics Limited

 

This looks really promiseing will have a chat with the audiologist when he returns from london(hes attending a seminar there for new treatment prospects for T and H patients in UCL)whats your honest opinion peeps will this treatment work??

 

Naturally Im hoping it will work but until there is no scientific data it doesn't really matter what I think. Anyway, even if this drug doesn't work the fact that it worked on rats means that they must have gotten smth right and this will open up opportunities for other treatments Let us know whether you are able to participate or not.

 

yeah will do guys hopefully he can organise this he conducts clinical trials there will let you guys know as soon as.....cheers

 

Suspect auditory ion channels implicated in other disorders....
Dr Charles Large, chief scientific officer of Autifony, said:
“The ion channels that we are targeting in our hearing loss programme are closely implicated in brain circuits which are believed to be dysfunctional in schizophrenia."
http://www.ncl.ac.uk/press.office/press.release/item/collaborating-to-treat-mental-illness

 

from their website;

Other Research
Given Autifony’s focus on modulation of Kv3 channels, which have also been implicated in other neurological and psychiatric disorders, there are opportunities for Autifony to investigate these other indications with compounds with different profiles.

Autifony was recently awarded a Technology Strategy Board grant to progress over the next two years the development of a candidate drug for the treatment of schizophrenia. Autfony are working with academic collaborators in Manchester and Newcastle Universities to obtain a greater understanding of the role of Kv3 channels in schizophrenia and to explore the potential benefit of Kv3 modulators in the treatment of this serious psychiatric disorder.

 

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-lt AISBL: www.hear- it.org/multimedia/Hear_lt_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 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. More specifically, a reduction in Kv3- like potassium currents in neurons of the dorsal cochlear nucleus has now been observed following acoustic trauma in rats, suggesting that reduced Kv3 function could contribute to the pathological process that is triggered by damaging noise (Pilati et al., 2011, Hearing Res., doi:
10.1016/j.hearingres.2011.10.008), and supporting the hypothesis that positive modulation of Kv3 channels in auditory brainstem nuclei could have a therapeutic benefit in patients suffering from noise- induced hearing loss. Finally, Fraglie X syndrome and autism are frequently associated with
hypersensitivity to sensory input, including auditory stimuli. Recent findings suggest that the protein coded by the FMR-I gene, whose mutation or absence gives rise to Fragile X syndrome, may directly regulate the expression of Kv3.1 channels in the auditory brainstem nuclei (Strumbos et al., 2010, J.Neuroscience, in press), suggesting that mis-regulation of Kv3.1 channels could give rise to hyperacusis in patients suffering from Fragile X or autism. Consequently, we propose that small molecule modulators of Kv3 channels in auditory brainstem nuclei could have a benefit in the treatment of disorders of hearing, including tinnitus and auditory hyper-acuity associated with Fragile X syndrome and autism.

 

will be talking to my audiologist about the trials in a few weeks will post updates if I can participate or not

 

http://www.fiercedrugdelivery.com/story/dod-funded-project-fuels-inner-ear-drug-delivery/2012-03-27

 

Hi guys I was talking to my audiologist yesterday about the new trials taking place in UCL i.e Autifony and so on as he was there last week discussing these with his colleagues.I also cannot participate in this trial at the moment as I am still under investigation which would not be accepted for a medical trial as it may skew results.Although he obviously could not go into too much detail about their studies there he did mention that these new treatments did appear very promising for treating T but there is more work to be done.He did also mention that they were testing lots of stuff there at the moment and that every few months there is a conference there where they discuss the latest research findings and treatments and that he would contact me with updates on their research.Thanks

 

Did she say that Autifony was promising?

 

We have discovered that a new drug may potentially be helpful for treatment of Fragile X syndrome. The drug acts on a protein called Kv3.1, which controls how much excitation a nerve cell can transmit to its neighboring nerve cells. Levels of Kv3.1 are markedly increased in mice bearing the FX mutation, and this elevation contributes to the over-sensitivity to sounds and other sensory stimuli that occur with FX, and is also likely to influence information processing in the brain. The action of the drug, provisionally called AUT, is to reduce the excitability of neurons from the Fragile X mice back to that observed in normal mice. This drug is in preliminary human trials this year.

The Slack potassium channel is widely expressed in the brain. Using neurons of the central auditory system, our laboratory has demonstrated that Slack is required for accurate timing of action potentials in response to synaptic stimuli. This channel is activated by the FMRP protein through a direct association of FMRP with the cytoplasmic domain of the channel itself. We have shown that levels of the Slack potassium current are reduced by about 50% in neurons of FMR1-/- mice. Treatment of neurons with pharmacological activators of Slack would be expected to restore levels of this current back to levels found in wild type animals. Using a combination of electrophysiological and biochemical assays, we have now identified five compounds that are effective activators of Slack channels and are now testing their specificity for this class of channels.
In addition, we have recently published work (see below) that has identified another potassium channel, Kv3.1, that is altered by loss of FMRP. The physiological role of this channel is to allow specific types of neurons to fire at very high rates. We have found that Kv3.1 mRNA is a binding partner for FMRP, and that in FMR1-/- mice, levels of this channel are elevated. Moreover, in the central auditory system Kv3.1 is normally expressed in an orderly tonotopic gradient, such that neurons responding to the highest frequency sounds have the highest levels of Kv3.1 channel. This orderly gradient is abolished in the absence of FMRP, causing all these neurons to have uniformly high levels of this channel. This finding suggests that auditory neurons are likely to be hyperexcitable in FXS individuals. In collaboration with a pharmaceutical company, we are therefore now investigating the actions of activators and inhibitors of the Kv3.1 potassium channel.


http://www.fraxa.org/toward-a-cure/funded-research/2013-2/kaczmarek/

 

Hi Dan he did mention Autifony as being promising in lab tests but without human data to back it up he was unable to say if it work.He also said that this was a new approach which scientifically had good credentials but to regard it as it is....an experimental drug.He also said that their lab results would have to have been very promising with a good proof of concept or UCL would not conduct the clinical trials there.UCL is one of the top research institutions and for them to be conducting the trials is very promising.

 

When can we expect any news on this?

 

High hopes for this! Cant wait to seee the efficiancy of it!

 

They will take time to crunch their numbers and will probably wait to publish it in a scientific journal of some sort. If they start planning Phase II trials, you can bet the safety profile was at least good. Keep in mind, this study is not looking for efficacy.

 

But do the people in the study have T? Cause if they were all cured I think they'd tell us regardless of what the intention was hehe

 

I think healthy people without T got it.

 

What a waste. Also, I don't buy that at all. If you're desperate enough to be a heatly guniea pig, chances are they're hiding stuff from you

 

The volunteers get paid for their risk.

 

Phase I is about testing the side effects. Thats why they choose healthy people. And yes, they get paid or they are just altruistic.

 

God bless those brave souls.

 

It shouldn't be considered too brave. Sure, it's the riskiest portion of the test, but the researchers likely aren't going to put anything into anyones ear that they think is going to cause any damage. The whole purpose of it is to make you feel better.

 

I thought that this treatment is in pill form? Am I wrong?

 

This is a pill form treatment.

 

Does "altruistic" mean a d*mn fool? Never heard that word in my life. Dumb down for the lay person?

 

the first one: http://www.oxforddictionaries.com/definition/english/altruism

 

Exactly