Noise-Induced Hearing Loss Restored in Mice Through Increased NT3 Production

Discussion in 'Research News' started by yonkapin, Oct 21, 2014.

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    1. yonkapin

      yonkapin Member Benefactor

      Location:
      Melbourne, Australia
      Tinnitus Since:
      March 2012
      This popped up on my Facebook feed today:

      http://www.medicalnewstoday.com/articles/284159.php

      Researchers from the University of Michigan and Harvard Medical School in Boston, MA, may be well on the way to finding new therapies that restore noise-induced and age-related hearing loss in humans. In a new study, the team describes how they recovered hearing in mice partially deafened by noise.

      In their study, the researchers explain how they were able to increase production of a protein called Neurotrophin-3 (NT3) in mice, which they found plays a key role in communication between the ears and the brain.

      NT3 allows sound signals to be sent from the ear to the brain. The protein is crucial in establishing a super-fast connection between the ear's hair cells and nerve cells - a connection the researchers call the "ribbon synapse." But this ribbon synapse can become damaged as a result of noise exposure or normal aging, which can lead to hearing loss.

      Boosting NT3 production in mice
      In their study, the researchers identified supporting cells in the inner ear that produce NT3. They set out to see what would happen if they increased production of NT3 through these supporting cells.

      They adopted a method called conditional gene recombination. This allows researchers to activate genes in particular cells by administering a drug that prompts the cells to "read" additional copies of a gene that have been inserted into them.

      For this study, the team used the technique to activate additional NT3 genes that had been introduced to the supporting cells of the inner ear in mice that had been partially deafened by loud noise.

      The drug tamoxifen was introduced to the supporting cells in the inner ear, which prompted them to produce extra NT3 protein. The researchers then tested the hearing of the mice through a test normally used in humans - the auditory brainstem response (ABR).

      The researchers found the mice that had experienced boosted NT3 production regained their hearing over a 2-week period, compared with mice that had not had additional NT3 production.

      According to the team, these findings indicate that NT3 production is important for making ribbon synapses, and that boosting production of this protein may restore noise-induced and age-related hearing loss.

      The potential to restore hearing loss in humans
      Corfas and his team say they now plan to investigate the role of NT3 in human ears and identify drugs that produce the same effect as the protein, offering the potential to restore hearing loss in humans.

      The researchers note that the gene therapy technique used in this study has the potential to work in humans, but that a drug-based method would be "simpler" and a drug could be repeatedly administered for as long as it takes for hearing to be restored. Corfas says he already has some drug candidates in mind.

      The researchers stress, however, that since the mice in this study were only partially deaf, it is unclear whether increased NT3 production would restore hearing in subjects that are fully deaf.

      But the team believes their findings are promising. Corfas says:

      "It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it's due to noise or normal aging. We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people. It's very exciting."

      Their findings may even reach further than hearing loss. The researchers say they may offer new strategies to treat neurodegenerative diseases, in which nerve cell connections are impaired.


      -

      This is the first time I've read anything about this approach, so apologies if something related to this has already been posted. Exciting stuff though, hopefully they can figure out a way to trial this approach on humans soon!
       
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    2. Champ
      Woot

      Champ Member Benefactor Team Tech

      Location:
      Boston, MA
      Tinnitus Since:
      1/2013
      Cause of Tinnitus:
      Acoustic trauma from headphones
      Must be nice to a mouse. Is there anything that hasn't been cured for them?
       
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    3. Ilija
      Breezy

      Ilija Member

      Location:
      Jagodina, Serbia
      Tinnitus Since:
      8/2014
      Cause of Tinnitus:
      Loud gig/year of loud headphone usage.
      Hahahaha well yes but.
      You have to think on the other side they're exposed to all that.
      When I read that they subject mice and give them Tinnitus on purpose, I felt sad for the poor mice :(
       
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    4. Champ
      Woot

      Champ Member Benefactor Team Tech

      Location:
      Boston, MA
      Tinnitus Since:
      1/2013
      Cause of Tinnitus:
      Acoustic trauma from headphones
      Yeah. You think thats bad? When theyre done with the mice they kill them.... poor fuzzies
       
    5. spingee
      Wtf

      spingee Member

      So why not start human trial immidietly?
       
      • Good Question Good Question x 1
    6. exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
      hi guys

      it might be good for the mice but it have several side effects :
      one of them

      Endometrial cancer
      Tamoxifen is a selective estrogen receptor modulator.[41] Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore endometrial changes, including cancer, are among tamoxifen's side effects.[42] With time, risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for 5 years.[43]

      The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine cancer while lowering the risk of breast cancer recurrence.[44] The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

      https://en.wikipedia.org/wiki/Tamoxifen
       
    7. AnnaW
      Vegged out

      AnnaW Member Benefactor Team Research

      Location:
      London
      Tinnitus Since:
      1998
      NT3 is a neurotrophin. BDNF can be increased through exercsie and learning, i wonder if this NT3 can be ncreased somehow...
       
    8. rainman
      Curious

      rainman Member

      Location:
      Tallinn/Helsinki
      But rats only got it for two weeks, no? Anyway, halleluja, this really came out of the blue!
       
    9. Ilija
      Breezy

      Ilija Member

      Location:
      Jagodina, Serbia
      Tinnitus Since:
      8/2014
      Cause of Tinnitus:
      Loud gig/year of loud headphone usage.
      Well although they have the most similarities they still have to adjust for humans.
      This proves that it can be done in mammals now they need to find what chemical in Humans causes this.
      Once they do the trials will start and hopefully we'll see people improving :)
       
    10. rtwombly
      Bookworm

      rtwombly Member

      Location:
      Southeast USA
      Tinnitus Since:
      01/2014
      Cause of Tinnitus:
      Unknown
      I wonder how this compares to Notch inhibition.
       
    11. exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
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    12. rainman
      Curious

      rainman Member

      Location:
      Tallinn/Helsinki
      anyone tried it for hyperacusis or hearing loss?
       
    13. hawkman7

      hawkman7 Member

      Tinnitus Since:
      01/03/2014
      Hello, I have been taking 6mg of astaxanthin for the last year but recently found out that 12mg is what has been found in clinical trials to help for many conditions and none of them mention T. I have started taking 12mg two days ago and just saw this info, I will update if any improvement is found as I was taking this when T started, but maybe the 12mg is what may show improvement.
       
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    14. exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
      Hi

      the study is showing effect on mice while they use 80mg/kg.they said in average of 30mg/kg,it should have effects.

      so basically your 6 or 12 mg /day doesnt make any sense.

      You should have a dose of 1/2 g a day to see a difference.

      are we agree on this?

      below is the research i m talking about

      http://academicjournals.org/article/article1380799074_Bai et al.pdf

      Also i ve read that vitamin d3 can increase nt-3 anyone have tried it for t?
       
    15. exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
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    16. spingee
      Wtf

      spingee Member

      I wonder how could they damage mouse cochlea without damage of hair cell, according to their research they managed to restore all hearing
       
    17. EatMoTacos
      Alone

      EatMoTacos Member

      Location:
      Texas
      Tinnitus Since:
      07/2009
    18. tomm
      Thinking

      tomm Member Benefactor

      Location:
      London, UK
      Tinnitus Since:
      10/2014
      Cause of Tinnitus:
      Acoustic trauma (club drumming)
      Been taking 44,000 IU (500 IU/kg loading doses) every so often and 10,000-20,000 IU most days for the past week or two after seeing an article about nerve growth factors. It's done diddly squat apart from making me twitch every so often and probably putting me close to having hypercalcemia. Been taking it with fatty food like milk and yoghurt as it's apparently fat soluble.

      If you have noise induced T, it probably doesn't matter if your nerves endings extend - the hair cells are gone. There's nothing for them to connect to. The rats and a lot of these other nerve related treatments only seem to work if you get to it within a day or two.
       
    19. skoupidis

      skoupidis Member

      Tinnitus Since:
      09/2014
      Cause of Tinnitus:
      Acoustic trauma or mvc
      Hi, what is your progress? Has astaxanthin helped you at all?
       
    20. hawkman7

      hawkman7 Member

      Tinnitus Since:
      01/03/2014
      Hello, I am still taking 12mg a day for inflammation but sadly no reduction in T.
       
    21. skoupidis

      skoupidis Member

      Tinnitus Since:
      09/2014
      Cause of Tinnitus:
      Acoustic trauma or mvc
      Thank you for your answer. Did you have hearing loss or hyperacusis? Did it help with that?
      I take it you take 12mg astaxanthin for a long period?
       
    22. hawkman7

      hawkman7 Member

      Tinnitus Since:
      01/03/2014
      Hello, no my hearing is fine, the T just appeared one morning out of the blue. I had been on it at the 6mg level for at least a year and started the 12mg several months ago. It has made no change to the T. Hope that this info is of some use to you.
       
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    23. skoupidis

      skoupidis Member

      Tinnitus Since:
      09/2014
      Cause of Tinnitus:
      Acoustic trauma or mvc
      Thank you for the info.
       
    24. kramdrol
      Caffeine

      kramdrol Member

      Tinnitus Since:
      1/6/2011
      Re astaxanthin, just tried it last night. After first two 6mg pills noticed a couple of micro dropouts in my high pitched T in right ear. Thought, Hmmmm... I'll take a couple more. Each "couple more" seemed to produce a very slight reduction, and after taking 10, the constant high pitch seemed to have changed to 'cycling' between lound and quiet. Was a bit excited, but we all know not to get our hopes up. This morning have roughly %30 reduction in volume, and was not effected by the sounds of the kettle boiling (my H is pretty bad too). Luckily I was taking coconut oil at the same time (to fight mouth fungus), because after reading up on astx this morning, it needs to be taken with fats. Will keep trying over the next few days and see what happens, and post some more.
       
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    25. Xorthian
      Balanced

      Xorthian Member Benefactor

      Location:
      Poland
      Tinnitus Since:
      Initial 2012. Massive spike 4/2015
      Cause of Tinnitus:
      Noisey Lifestyle. Increase from infection.
      So you tried 60mg at once pretty much? Or you poped one 6mg pill each hour or half an hour? whats your body weight? I might check this out because of pure deseration :)
       
    26. kramdrol
      Caffeine

      kramdrol Member

      Tinnitus Since:
      1/6/2011
      Took 10 over a period of a couple of hours, in the middle of the night. Started slow in case I had a reaction to it. I weigh 70kg. It was on an empty stomach, apart from some coconut oil I had been taking for an outbreak of fungus on my tongue. I took it because my T and H had ramped up by %50 or so since coming off Lyrica. I could barely listen to the TV/radio or the beep my car does when I put it in reverse. Will take less tonight, maybe 5 or so, and .... see what happens.
       
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    27. kramdrol
      Caffeine

      kramdrol Member

      Tinnitus Since:
      1/6/2011
      Took 5 x 6mg Astax straight after dinner, then 3 more at bed time with some coconut oil. Total of 48 mg. T reduced to 4 or 5 out of 10. In the morning now, T is 3 at most. Was sitting at 8 before started Astax. H is no question improved, but still there. Hard to put 'number out of 10' on it. Currently listening to bedside radio without usual ear plugs or trauma. Will take same dosage tonight. Side effects: huge mood lift, brain feels switched on, BPH symptoms diminished.
       
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    28. Xorthian
      Balanced

      Xorthian Member Benefactor

      Location:
      Poland
      Tinnitus Since:
      Initial 2012. Massive spike 4/2015
      Cause of Tinnitus:
      Noisey Lifestyle. Increase from infection.
      I can only find astax with other stuff in tabs like vitamins and lutein for example. Can you tell me brand name of astaxin you take? Link to amazon or someething?
       
    29. kramdrol
      Caffeine

      kramdrol Member

      Tinnitus Since:
      1/6/2011
      I'm in Australia, the brand is MicrOrganics, it's 6mg astax, vit E 10 mg, Linseed oil 400 mg, Oleic, Linoleic, Linolenic acid. It sort of sounds like you get most of this from the extraction process, rather than all added seperately. Or maybe they are added to help absorbtion, cos astax is fat-soluble? It is the only brand I can buy at health stores here, so I wasn't too fussed. I had a quick look at it seems available online. T currently 3, H maybe %20 better. I would like H to be even less, but it was so bad, any improvement is fantastic. Just buy some and try it dude!
       
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    30. kramdrol
      Caffeine

      kramdrol Member

      Tinnitus Since:
      1/6/2011
      Still going strong, after 10 days. Take 7 * 6mg astax at 5pm with coconut oil. Take a few good nips of tart cherry concentrate at bed time, and I am falling to sleep, and staying asleep better than I have in many years. T drops off to 3 or 4 at night, and is similar in the morning. Starts to pick up again in the afternoon, before next hit of astax. The unknown long term side effects, or unknown long term efficacy is just something I live with. It would be great to know that astax will keep working long term with no ill effects, but what can we do? If I start to turn pink like a Flamingo or a Salmon than I may need to take a break :) (astaxanthin is what makes them pink)
       
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