The Mechanism that Causes Noise-Induced Tinnitus Found and Drug that Can Prevent It

PITTSBURGH, May 27, 2013 –
An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine. The findings, reported this week in the early online version of the Proceedings of the National Academy of Sciences, reveal for the first time the reason the chronic and sometimes debilitating condition occurs.

An estimated 5 to 15 percent of Americans hear whistling, clicking, roaring and other phantom sounds of tinnitus, which typically is induced by exposure to very loud noise, said senior investigator Thanos Tzounopoulos, Ph.D., associate professor and member of the auditory research group in the Department of Otolaryngology, Pitt School of Medicine.
“There is no cure for it, and current therapies such as hearing aids don’t provide relief for many patients,” he said. “We hope that by identifying the underlying cause, we can develop effective interventions.”

The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells — they fire impulses even when there is no actual sound to perceive. For the new experiments, they took a close look at the biophysical properties of tiny channels, called KCNQ channels, through which potassium ions travel in and out of the cell.
“We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity,” Dr. Tzounopoulos said. “These KCNQ channels act as effective “brakes” that reduce excitability or activity of neuronal cells.”

In the model, sedated mice are exposed in one ear to a 116-decibel sound, about the loudness of an ambulance siren, for 45 minutes, which was shown in previous work to lead to the development of tinnitus in 50 percent of exposed mice. Dr. Tzounopoulos and his team tested whether an FDA-approved epilepsy drug called retigabine, which specifically enhances KCNQ channel activity, could prevent the development of tinnitus. Thirty minutes into the noise exposure and twice daily for the next five days, half of the exposed group was given injections of retigabine.

Seven days after noise exposure, the team determined whether the mice had developed tinnitus by conducting startle experiments, in which a continuous, 70 dB tone is played for a period, then stopped briefly and then resumed before being interrupted with a much louder pulse. Mice with normal hearing perceive the gap in sounds and are aware something had changed, so they are less startled by the loud pulse than mice with tinnitus, which hear phantom noise that masks the moment of silence in between the background tones.

The researchers found that mice that were treated with retigabine immediately after noise exposure did not develop tinnitus. Consistent with previous studies, 50 percent of noise-exposed mice that were not treated with the drug exhibited behavioral signs of the condition.

“This is an important finding that links the biophysical properties of a potassium channel with the perception of a phantom sound,” Dr. Tzounopoulos said. “Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans.”

The KCNQ family is comprised of five different subunits, four of which are sensitive to retigabine. He and his collaborators aim to develop a drug that is specific for the two KCNQ subunits involved in tinnitus to minimize the potential for side effects.
“Such a medication could be a very helpful preventive strategy for soldiers and other people who work in situations where exposure to very loud noise is likely,” Dr. Tzounopoulos said. “It might also be useful for other conditions of phantom perceptions, such as pain in a limb that has been amputated.”

Read more at http://scienceblog.com/63396/causes...drug-that-can-prevent-it/#ddfbTU4DttRJVUyS.99

 

Very interesting find Mick. It seems that much of the cutting edge research these days is pointed to these potassium gated channels as the target for treating tinnitus. It would be interesting to see what if any effect it has on those with the chronic form of tinnitus.

That AUT3 compound Autifony Therapeutics has developed for chronic tinnitus targets a potassium channel as well. It would be interesting to know more about what particular potassium channel(s) they think are responsible for the development of tinnitus. I do hope that there is some therapeutic benefit for those of us with chronic tinnitus, I'd hate to be left out in the wind. Any advancement in the understanding of the condition will inevitably progress research toward a treatment for chronic tinnitus, though.

 

It seems that this drug acts on the Kv7 potassium channel as opposed to the Kv3 channel family that the Autifony Therapeutics compound targets. It will be interesting to see which if any compounds actually can treat tinnitus in a meaningful way.

 

This is definitely some good news. There have been a couple good tinnitus updates towards treatment possibilites within the last week (including the Autifony Therapeutics compound). Both of these compounds in question retigabine, and the AUT3 copmound Autifony uses, target potassium channels in the DCN. It is interesting to see science converging into a possible area.

This is the same article that Mick posted last night. Perhaps Markku can merge the threads.

 

Preventative medicine? Let 'em walk a mile in OUR sh*t!

 

Autifony seems to think their compound that targets another but similar family of potassium channels suppresses chronic noise induced tinnitus. I don't think the investigators looked into chronic applications for this study at all, though. Everyone wants to address acute tinnitus because I think that's where they feel the best option for treatment at this point is. Baby steps I guess.

 

Good news is any news in this Terrible affliction....at least there is news and it continues. I would like to see a 10-fold increase in the news and more in different chemicals as well. Sound thereapy is no more than snake oil i have found thus something that can be measured before and after treatments is welcomed. please keep up the great news. To all you heros that continue to search and post your findings here i salute you.

V

 

Here's a story which was in the daily mail

http://www.dailymail.co.uk/health/a...yperactivity-cells-ear.html?ito=feeds-newsxml

 

"To prevent", "for acute stage"... Perfect... Yes, I am ironic...

 

Even if it is for acute tinnitus how many people who expose them self to loud noise would think to go to the doctors to get a drug to prevent tinnitus. Plus even if the tinnitus started and they never had tinnitus before they might just think it will go away in a few days and again not go to the doctors. So even if a drug is developed to prevent tinnitus doesn't mean that there won't continue to be be people who get chronic tinnitus!
Hope this makes sense

 

acute period is up to 3 months... Everyone will see doctor until that...I suposse...

 

I know it's disappointing to people on here, but I'm not complaining about a treatment for acute tinnitus that's in the works. What if your tinnitus gets worse someday and the treatment is available? You could go in and get that treatment and maybe it will help keep your tinnitus from getting worse. That's huge.

Any kind of meaningful tinnitus treatment will also spur more research and development into treating more etiologies of tinnitus. There's many millions of chronic tinnitus sufferers out there, and it's hard to ignore that kind of treatment potential.

As far as a cure goes, I don't think our tinnitus will ever be completely eliminated by a treatment. Maybe treatments will alleviate much of the loudness or pitch, but I doubt they'll make it go away. I think what eventually will make tinnitus go away is the ability to regrow hair cells of the cochlea. Check out the hearing restoration project if you're bored. They've got a good plan in the works.

What is encouraging about restoring hair cells vs regrowing limbs or curing cancer is that nature has already figured out how to do it for us. Scientists have a model to study of multiple organisms that readily regrow their inner ear hair cells after damage. That's huge. They've got a map, they just need to figure out how to read it basically. That's why I have great hope that hair cells will be able to be regenerated in a meaningful way to restore hearing for many types of hearing loss. It's down to basically figuring out what molecular pathways need to be suppressed or stimulated to encourage regrowth of new hair cells. Once that is done, it's simply figuring out how to deliver that treatment to the inner ear, which several technologies are already looking into despite the fact that the science for treatment delivery is not there yet either.

The hearing restoration project thinks they can get it done in 10 years possibly, or at least get to the point where they have clinical trials rolling by that time. What one needs to consider is that the field of molecular biology and the sciences in general have been expanding ever more rapidly as time increases. What used to take 5 years in the 90's takes 6 months to a year now, in terms of genetic sequencing. As time goes by, the tools available will become more robust.

That's all fine and dandy, but doesn't do much for us now though. I count myself lucky every day that maybe by the time I'm 40 there will be solid treatments available. That's much better than people 50 years ago could have ever dreamed of.

 

Well H. lets be honest, today and 50 years ago, it is the same situation with curing T. No real drug, no real treatment, same advice from ENT-live it it! etc... only new is internet, and more talking about it, like we are doing here...

 

The horse comes before the cart, doesn't it?
http://www.autifony.com/autifony-pipeline.asp - Phase 1 Clinical trial for treatment of chronic tinnitus
http://www.aurismedical.com/p/therapies/am_101.php - Phase 3 clinical trial for treatment of acute tinnitus
http://audiontherapeutics.com/hearing-loss-program/
http://www.fiercebiotech.com/press-...ver-novel-treatments-sensorineural-hearing-lo

That's just a sample of some of the research going on in the private industry. That doesn't include what's going on in the academic world, such as the Hearing Restoration Project. I think you could say that's leaps and bounds more than 50 years ago.

 

Yes H. but all of that is future, no one garanties that any of these drugs/treatments will be productive. I hope that they will, all of them, I would do everything for it...
But what I say, 1963-2013- there is same treatment for T. actually there is no treatment that works.

2014, 2015...2020, who knows... i pray for it... but last 50 years nothing :/

 

Yes Markku, that is correct. I hope that in 2014. will be ONE fine treatment that can cure at least 40% of all people that have T. But really cure!

What I say, sadly say, in 2013. we have no better solution than in 1963...not exactly, but in a fact, that is realistic...

 

Of course I would prefer a cure, but any progress, even preventative, is awesome.

 

Hi all

here is a link to a page that summerises the development so far in human cochlear hair cell regenration. It has links for those who want to read further. Hope this brings some light to our grey days

http://www.hearinglossweb.com/Medical/cures/hair/hair.htm

Cheers

 

Has anyone thought about going to their doctor and asking for a prescription for retigabine? Seeing how this drug has already been approved (although not for tinnitus) maybe there would be a doctor willing to try it off label. Maybe not. We can't know until someone tries though!

 

The thing with Retigabine is that it comes with some serious side-effects:

http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON296401

I am not sure a neurologist would be altogether comfortable prescribing this drug off-label. But if anyone does try Retigabine for tinnitus, please report back the results!

-Golly

 

Well, hell. If I wasn't participating in a trial already I might try this myself. I could at least ask the doc if they would let me. Maybe that's what I'll do next. I could join the blue man group if it helps treat tinnitus.

 

I am in communication with a fellow tinnitus sufferer who told me he is asking his doctor for Retigabine script in the near future. I'll report back when I hear the outcome. -G

 

Golly, did you ever hear back from you friend about the outcome of his request from his doctor? I would be very interested to follow any developments !

 

@Hudson;

Thanks for reminding me. I will e-mail him this morning. I'll let you know what I find out. -G

 

I'm 4 months in. Should I try an epileptic medicine pill?

 

Erlend,

That is honestly up to you and your doctor. These threads should not serve as any kind of basis for medical advice. If you find something interesting here, it may well be worth discussing with your doctor. If your doctor feels like there is no major risks, maybe he or she will write a prescription for you. If that is the case, I would definitely be interested to hear what your experience is.