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briann

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Posts: 141
Reply with quote  #1 
Let me make one thing clear first. Retigabine (Trobalt, Potiga) has serious side effects so I’m not encouraging people to try this. However, I think anything that can reduce tinnitus and hyperacusis severity provides a clue and even hope for medicinal treatment in the future. Many members of the tinnitus talk forum expressed reduction in both tinnitus and hyperacusis when taking Retigabine. Some comments from the thread are below,

General Discussion:
http://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-general-discussion.5074/

User Experiences:
http://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-user-experiences.6047/

“I got some more and yeah T is low and h is gone”
 –User A

“yes, my hyperacusis disappeared completely” –User B

 “About hyperacusis: Surely not worse. Yesterday I went to the gym, when it used to with this metallic sound of the weights. I barely was annoyed – the same as before my T appeared one year ago” -User C

 “Mine went down by a half to a third. I still have to plug when washing up plates, … car horns still. However being able to turn the squeaky tap on in my bathroom without going for plugs is great.” –User D

 “It’s helped my hyperacusis to the point I can run the dishwasher just a few feet away which was torture before, and every now and again I forget about my tinnitus completely.” –User E

 

I saw 3 users where hyperacusis got worse. One stopped taking the medication and the H went back to normal. I couldn’t tell for the other two. There is also talk of the negative side effects which you can see by clicking on the thread link above.  I’m focusing on the positives because I see this as a clue, not an answer.

 ----------------------------

From my research, the following is my understanding of what is going on and I welcome corrections.

 

Most of the excitement for tinnitus drug development is behind drugs that are voltage-gated potassium channel activators. Voltage-gated potassium channels serve to reset the neuron potential. Introducing activators for a voltage-gated potassium channel will reduce the activity of the neurons that have this type of potassium channel. There are 40 different types of voltage-gated potassium channels. 

Retigabine activates 4 of them called Kv7.2-7.5.  These channels are used throughout the body which may contribute to the significant side effects. They are also included in the cochlea and auditory pathways through the brain stem. 

Kv7.4 is mostly focused in the cochlea and auditory pathways (although still present in other places in the body). Kv7.4 is also the channel activated to minimize activity of what some researchers are hypothesizing to be pain receptors in the cochlea (Type II afferent neurons from OHCs). I know nothing about drug development, but this makes me wonder what a drug that only activated Kv7.4 would do.

Another drug that is gathering a lot of excitement in the tinnitus community is a drug from Autifony called AUT00062.  This operates on Kv3.1 voltage-gated potassium channels. The hope is that this is more selective than drugs like Retigabine. We’ll have to wait and see if this works on tinnitus and/or hyperacusis and what side effects will accompany it.

If we eventually find a drug to greatly reduce hyperacusis, it will almost certainly have been developed for something else. If medication is successfully developed for tinnitus, I'm hoping that it works for hyperacusis as well.

UPDATE:
University of Pittsburgh has recently developed a drug called SF0034 that only activates Kv7.2 and Kv7.3. Since this activates only two potassium channel types it may have fewer side effects but we will need to wait and see. They find both SF0034 and Retigabine can prevent tinnitus from developing in mice when administered shortly after noise exposure. (ARO 2015 Abstract)

University at Buffalo has a 2011 study that shows Maxipost reversed behavioral evidence of tinnitus in rats after tinnitus had already developed. Maxipost activates the same potassium channels as Retigabine, Kv7.2-Kv7.5.

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Aplomado

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Reply with quote  #2 
That doesn't sound very safe at all, unfortunately.
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briann

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Reply with quote  #3 

Indeed Retigabine has serious side effects.

I was trying to make two points.

1. There may be a way to learn from this drug so that one could be developed with fewer side effects. 
2. Given that it is unlikely a drug will be developed for hyperacusis specifically, recent efforts for developing a drug for tinnitus patients may apply to hyperacusis patients.

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Rob

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Reply with quote  #4 
In the University of Pittsburgh School of Medicine study, retigabine wasn't found to reduce tinnitus and hyperacusis.  Rather, the researchers concluded the drug may have prevented tinnitus from developing after mice were exposed to 116 decibels for 45 minutes.  (A previous study had concluded that half the mice subjected to this volume of sound for this length of time developed tinnitus.)  After 30 minutes of exposure to this very loud sound, half the subjects were administered an injection of retigabine twice a day for five days.  The researchers used a startle experiment to try to determine if the subjects had developed tinnitus.  Half the subjects who did not receive retigabine showed behavioral signs of having tinnitus, as determined by the startle experiment. 

The study's authors regard the use of this drug, which is used for epilepsy, as a preventative strategy for people who are typically exposed to very loud sound.  There is absolutely nothing in the study to suggest the use of retigabine reduces tinnitus severity in people who already have the condition and nothing in the study to suggest it can reduce or prevent hyperacusis.

Rob
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briann

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Posts: 141
Reply with quote  #5 

The results from the University of Pittsburgh are even more interesting! They show when Retigabine is used shortly after noise exposure tinnitus was prevented from developing altogether! With these side effects, I would think that is the most realistic way to use this drug. I’d be curious to see if this helps prevent the development of certain types of hyperacusis if taken shortly after exposure. 

Hyperacusis is a rare condition and so I'm not surprised it's not always included in tinnitus studies. Hopefully the exposure we are getting with HyperacusisResearch.org presenting at the Association for Research in Otolaryngology conferences will help. However, yes, it would have been nice if they showed results of growth in Acoustic Startle Reflex. That has been shown in one study not to correlate well in humans with hyperacusis, but it seems to be all we’ve got.

The study shows Retigabine can prevent tinnitus from developing when given after exposure which reinforces the discussion on the forums that it has potential to impact tinnitus (and in the case of the forum, reduced tinnitus in people who already have the condition).

I did not see anything in the paper proving Retigabine will not help those who have already developed tinnitus. It seemed those who stopped taking the drug in the forum had tinnitus and hyperacusis levels return so it likely is not as effective as using it at the onset if the results of the paper translates to humans. Without a clinical trial available for Retigabine applied to Tinnitus and Hyperacusis, I still see this as a promising development. Again, i'm not encouraging people take Retigabine.

It looks like the University of Pittsburgh will try to develop a drug specific to Kv7.2 and Kv7.3. I find this all really encouraging. 

 

 

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Rob

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Reply with quote  #6 
It doesn't follow that if a drug may prevent tinnitus from developing in some rats it may reduce tinnitus and hyperacusis in people who already have these conditions.  The authors weren't testing for the second thing.  They were only testing for the first.

Rob   






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Aplomado

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Posts: 711
Reply with quote  #7 
Briann, I'm glad you posted this... if it weren't for the possible side effects I'd try and get a script and try it myself.

The anectodotes on the other page are interesting to say the least.

Keep us informed please.
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briann

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Posts: 141
Reply with quote  #8 
Hi Alpomado,

Hopefully someone will find a way to reduce those side effects while maintaining efficacy. There seems to be interest in this area. John Hopkins developed something that selects only Kv7.2 andKv7.4 (although it can't be taken as a pill) and University of Pittsburgh actually finished developing a Kv7.2, Kv7.3 selective drug. I'd like to see T and H research using those.


Hi Rob,

It looks like there may have been confusion regarding my first post.

I never brought up the University of Pittsburgh study although I’m glad you did. I brought up a study from John Hopkins that showed Retigabine prevented excitation of the type II afferents from OHCs. Some researchers suspect these neurons may be pain receptors. I looked up Retigabine after reading that John Hopkins study and that is how I found the tinnitus forum thread on Retigabine in the first place.

I brought up several members of the forum that showed hyperacusis improvement (there are even more who have shown tinnitus improvement). You can think of them as mini case studies. Reading through some of the 140 pages of forum posts gives the feel that this is more than placebo effect, especially in the case of tinnitus. Posts about hyperacusis improvement were more dramatic than I’m used to seeing for placebo effect. Certainly not grounds for drug approval but more than enough for hope and curiosity.

You introduced the University of Pittsburgh study and then said it doesn’t prove the claims of those on the forum. I agree with you. It certainly doesn't disprove them either. 

However, I think your introduction of that study brings some interesting information. It shows that Retigabine has even more potential than what was mentioned in the forum. The study shows Retigabine may be able to prevent tinnitus from developing altogether and makes me wonder if it could even prevent hyperacusis from developing since the two conditions, although different, generally occur together. The study also reinforces the theme of the tinnitus forum that this drug can make a real impact on tinnitus.

 

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Rob

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Reply with quote  #9 
Hey briann.  Thanks for the clarification. 

To clarify my first post, I was responding to the title of the thread that this drug "reduces tinnitus and hyperacusis for some" and relating that to the only study I'm aware of with regard to retigabine and tinnitus.  The authors of that particular study didn't claim this drug would reduce tinnitus or hyperacusis, nor have they tested their findings on people. 

From what I can tell, the view that this drug will reduce tinnitus and hyperacusis in some comes from some folks posting on a tinnitus forum.  I don't regard these posts as "case studies" but as anecdotes with a lot of unknowns.  That particular site also appears to have a small contingent of misinformed people who strongly believe the application of low level lasers not only improves tinnitus and hyperacusis, but improves hearing as well. 

Rob   

 

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briann

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Posts: 141
Reply with quote  #10 
I can understand not wanting people to get wound up over a forum thread. However, when comparing this Retigabine thread to others, like the laser treatment for example, it seems the self reported cases presented are more numerous and more dramatic in terms of improvement. Adding that research shows this same drug can prevent tinnitus from developing and prevent excitation of what some are considering to be pain receptors in the cochlea further stokes curiosity. On the other hand, research has shown that laser treatment is not effective. I think it is healthy for both sufferers and researchers to maintain interest in this direction. I don't see a need to kill the buzz just yet.
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Rob

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Reply with quote  #11 
I think you're right. 

Rob
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Aplomado

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Reply with quote  #12 
So... anybody willing to risk their eyes & give this a try?  I'm waiting for someone else to do this first....
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dave2

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Posts: 96
Reply with quote  #13 
Phase 2 clinical trials for Autifony's AUT00063 have just begun in the United States. They are now recruiting volunteers now for Florida and Utah. Soon to follow are Kentucky, Minnesota, Mississippi,  New York, Oregon, and Tennessee. Eligibility criteria and contact info to volunteer at the link:

https://clinicaltrials.gov/ct2/show/NCT02345031

Would be great to have some interested H people who meet the criteria volunteer for this trial and be able to report back any improvement in H.

AUT00063 is a Kv3 modulator that is being tested in the UK on Tinnitus and in the US for hearing loss. Will be fascinating to hear anecdotal information from volunteers in both countries as the trials roll out if the drug reduces / eliminates H for some.
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