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Suicidal
- Thread starter jeremy06
- Start date
Member- Jan 25, 2013
- 3,574
- Tinnitus Since
- 2008
- Cause of Tinnitus
- TMJ disorder, airplane barotrauma, noise exposure.
Is @FGG around? Or anyone who wants to answer questions on the regeneration drugs(?), treatment, tech/science of regenerative treatment of the ear especially if it applies to tinnitus and hyperacusis.
I have some questions.
This isn't my question but I was wondering how many companies and researchers are working on this?
I only know of this one:
Frequency Therapeutics Commences Dosing in its Phase 2a Study of FX-322 ...
I have some questions.
This isn't my question but I was wondering how many companies and researchers are working on this?
I only know of this one:
Frequency Therapeutics Commences Dosing in its Phase 2a Study of FX-322 ...
- Jan 25, 2013
- 3,574
- Tinnitus Since
- 2008
- Cause of Tinnitus
- TMJ disorder, airplane barotrauma, noise exposure.
Trobalt is off the market. It had serious side effects. It should not be considered even if it was still available. That ship has sailed and it sunk.
Oh I wasn't aware Trobalt was off the market, but it was available in most pharmacies in Spain w/o prescription...
Regenerative medicine companies:
Hair cell regeneration:
Frequency FX-322 (inner and outer hair cells)
Phase 2a
Otonomy OTO-6xx (pre clinical for severe losses)
Novartis CGF-166 (this one was surgically infused and my personal opinion is I think they completely screwed up by making it a cochleostomy instead of a canalostomy, a newer method surgical method that doesn't damage the cochlea) because they probably damaged more hair cells than they repaired. I think if they re-do the trial with the latter, they may have something). Phase 2.
Pipeline PIPE-505 (Outer hair cells only and synapses)
Pre-clinical.
Decibel (? Small molecule regeneration. Pre-clinical).
Synapse drugs:
Otonomy OTO-413
Phase 2
There is also:
Akouos -- they have something pre-clinical that seems like a much better version of what Novartis was trying to do. They seem more focused on genetic hearing loss but apparently, they are using the same method pre-clinically for acquired hair cell loss.
Beyond regeneration, Dr. Thanos is working on an ion channel drug that is a safer and more effective Trobalt (which people on Tinnitus Talk got relief from but also a ton of side effects). I believe people with tinnitus and hyperacusis both found relief with Trobalt. Pre-clinical.
Autifony has some ideas for this too. Also pre-clinical. But I need to find out more info.
C
Capstan
Guest
I don't know why you guys think growing back hair cells will solve everything relating to noxacusis and facial nerve pain. I don't think it will.
I think it will absolutely help tinnitus and loudness hyperacusis but I'm sort of with you as it being more unknown when it comes to noxacusis because I'm not sure if restoring the outer hair cell and stopping the ATP leakage will stop the pain fibers sensitization. However, over time it might.
I think ion channel drugs (not necessarily just ear related) are a more promising avenue overall for noxacusis. But I'm really not at all sure. Just my gut feeling.
Current Promising Treatments:
Regeneration Therapies:
Cochlear degradation has a strong correlation with tinnitus, therefore, regenerating these structures should benefit tinnitus patients.
Frequency Therapeutics - FX-322 (Phase 2a): Uses 2 molecules which, when injected in the ear, partially reprogram support cells into creating hair cells, while not depleting support cells. When created, hair and support cells release NT3/BDNF to attract neurons, which make the synapse components to communicate. They also added a tinnitus experimental arm and are doing a podcast with tinnitus talk.
Audion Therapeutics - LY3056480 (Phase 2): Uses a molecule which, when injected in the ear, causes support cells to trans-differentiate into hair cells. This does deplete support cells, so multiple uses will have diminishing efficiency. Results are said to come out at the end of April.
Hough Ear Institute - siRNA (Preclinical): Uses siRNA (silencing RNA) which, when injected in the ear, causes support cells trans-differentiate into hair cells. This does deplete support cells, so multiple uses will have diminishing efficiency. In animal testing, hair cells regenerated the synapse components to communicate.
Pipeline Therapeutics - PIPE-505 (Going to Phase 1): Uses gamma secretase inhibitor which, when injected in the ear, causes support cells to trans-differentiate in synapses and hair cells. This does deplete support cells, so multiple uses will have diminishing efficiency. Treatment for tinnitus was shown in their patent.
Hough Ear Institute - NHPN-1010 (Going to Phase 2): Uses a antioxidant (HPN-07) and molecule (NAC) which, when swallowed in pill form, regenerates hair cell synapses in chronic hearing loss models. Also has shown efficiency in animal tinnitus models.
Otomony - OTO-413 (Phase 1): Uses a protein (BDNF) which, when injected in the ear, causes regeneration of synapses. Hidden hearing loss is the loss of synapses connected to hair cells, thus, regenerating synapses can treat this, also with possibly helping tinnitus.
Neuromodulation Therapies:
Neuromadulation has shown efficiency in reducing or eliminating tinnitus by reducing hyperactivity in the area of the brain associated with tinnitus.
University of Michigan - Depending on which has the most effect on your tinnitus, they places stimulation around your head, jaw, and neck. This along with sound timing has shown a 12db tinnitus decrease in their testing.
University of Minnesota - Uses targeted timing based on your tinnitus/EEG to stimulate areas of your neck/head/jaw along with customized treatment for sound timing. Would be the most effective and has cured @kelpiemsp of his tinnitus.
Lenire - Stimulate the tongue along with sound timing has had some positive effects on people tinnitus.
Ion Channel Therapies:
Prof. Thanos Tzounopoulos - RL-81 (Preclinical): A drug based off Trobalt (Retigabine), which has shown positive effects on tinnitus, although having severe side effects. RL-81 aims to reduce side effects drastically by being more targeted, while also having a 15x potency in the targeted area, potentially reducing tinnitus.
There are more treatments coming as well but these are the most popular right now, so don't give up hope! All are planned to release within the next 5-10 years or less.
- May 2, 2020
- 202
- Tinnitus Since
- 01/2019 T, 04/2020 H
- Cause of Tinnitus
- Headphones/Car Alarm/Immune Response?
I think there's maybe a 1 in 3 chance. One argument is that we didn't have it before the cochlear damage, so if the brain/nerves haven't permanently internalized these sensations then they should dissipate with hair repair. Other types of nerve pain tend to resolve once the core issue goes away, and the fact that noxacusis is influenced by noise rather than happening randomly shows that there is still a relationship going on there.
However, there are so many things involved that I doubt the solution will be so simple. The trobalt successor and nav 1.7 inhibitors are more promising, but these are 5-8 years away. Might as well be a lifetime.
Anima
Member
- Mar 22, 2016
- 202
- Tinnitus Since
- Feb 2004
- Cause of Tinnitus
- Noise trauma/metronidazole+kanamycin
Trobalt is totally forbidden in Spain, it cannot be obtained even for hospital use. It is no longer manufactured, which presumably applies to the rest of the Union. Regards.
Site one is starting a clinical trial for post op pain using a NAV 1.7 inhibitor this year:
https://adisinsight.springer.com/trials/700300140
I think noxacusis makes a great case for expanded/compassionate use of this drug while it is in trial if the company would consider that off-label use at this time.
For those who don't know people born without NAV 1.7 receptors cannot feel any pain at all. This drug would make people with normal pain receptors like them, completely pain free.
Do you have any hard numbers on the truckloads of money reportedly going towards CBT? I think there's very little ongoing research still focussing on CBT.
That should probably be enough of a warning to steer clear of Trobalt. It was like a blanket bombing approach towards tinnitus anyways.
- May 7, 2015
- 1,045
- Tinnitus Since
- 29.09/2014
- Cause of Tinnitus
- Acoustic trauma using headphones
I´ve been refered to an ENT surgeon to have my tympanic muscle cut. This as an effort to help with my severe noxakusis.
The reasoning behind it is that it acts up as a startle muscle and irritates the trigemenal nerve that brings on the pain even by every day noise.
Anybody have any knowledge of this?
The reasoning behind it is that it acts up as a startle muscle and irritates the trigemenal nerve that brings on the pain even by every day noise.
Anybody have any knowledge of this?
- Sep 21, 2016
- 1,051
- Tinnitus Since
- 2011 - T, 2016- H, relapsed 2019
- Cause of Tinnitus
- noise-induced
Yeah I think there's reason to be cautiously optimistic about HC regeneration however I share some of the reservations mentioned by Contrast and FGG. The thing that concerns me, particularly with chronic cases of noxacusis, is the possibility of central sensitisation therefore the new trobalt/nav 1.7 inhibitors may be better suited to tackling it. I've read a bit about nav 1.7 inhibitors and it's one of those areas of science where there have been a lot of challenges to overcome but it's so great to hear that there are now drug candidates about to enter clinical trials. I hope they succeed.
I have only read about the Silverstein surgery for hyperacusis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100801/
And @Marko Nakovski has done it. But I don't think that it involves the cutting of some ear muscles.
This is summarized really well (can't believe I left out Hough in mine)! I will upvote your succinct summaries everytime I see them.
FYI though, Audion did release their results but only vaguely. They mentioned 30% improvement in hearing parameters (which parameters?) and are reportedly working with their partners to tweak the drug for further study. Their method has a lot of issues compared to say Frequency because it depletes supports cells and makes a hair cell like cell that may be closer to a vestibular cell than a cochlear hair cell. But the fact that even then, they got some hearing improvement is a good sign. Frequency does not deplete support cells and makes phenotypic hair cells.
- Dec 21, 2019
- 319
- Tinnitus Since
- 2014, 10/2019
- Cause of Tinnitus
- School Band, Noxious Car Radio
I think it will benefit research to be able to see how regeneration impacts neuro inflammation from extreme noise (Is it in response to hair cell damage, or does the signal damage the nerve itself?) and test the heir-cell-leaking-ATP hypothesis. Hair cells are probably not the silver bullet to all auditory pathologies, but it expands the potential for research.
- Oct 19, 2019
- 862
- Tinnitus Since
- 2016/2017/2019
- Cause of Tinnitus
- Unknown
Is it okay with you if I translate this and share in a local Facebook group? If yes, how would you like to be cited?
- Sep 21, 2016
- 1,051
- Tinnitus Since
- 2011 - T, 2016- H, relapsed 2019
- Cause of Tinnitus
- noise-induced
Yeah, it will be really interesting to see what happens in further clinical trials. There's a really interesting explanation of the potential mechanisms underlying painful hyperacusis given by Paul Fuchs from Johns Hopkins from an interview he gave in 2016.
Q. We'll start talking now about tinnitus. Many patients report that sound gives them pain or they perceive hyperacusis, but there is also a link with tinnitus. Many patients report more sound exposure gives them louder tinnitus, hyperacusis and pain. Can you comment?
A. So this is where you start to see the interplay between peripheral changes —- the way the sense organ itself changes — and the way the central nervous system follows that up with some forms of plasticity and more complicated kinds of changes. By comparison to pain in the skin or in the body generally, we know that there are changes in the sensitivity and excitability of the nerve fibers that innervate skin — when you have a kind of painful nerve condition in the skin — but there are also central changes where connections between neurons become stronger or weaker. And so tinnitus is probably more like phantom pain, which I'm sure you may have heard of — that people who have lost a digit or a limb can report painful feelings in the missing limb.
So in conditions where the auditory periphery is no longer providing normal input, where you have some degree of hearing loss, then the brain begins to kind of self-generate activity as a replacement for the lost activity. This probably results from an imbalance in the input provided by what one would call the cognitive nerve fibers. In the somatic nervous system, for example, that means the fibers that tell us about touch and limb position, the cognitive inputs about our body — vs pain fibers. We don't really want to think about that pain. We just want to get away from it. So pain fibers initiate withdrawal symptoms.
And in the normal nervous system, there is a balance between input coming on pain fibers and input coming on the cognitive, touch, motion or other fibers. And there's even a pretty well established principle that those cognitive nerve fibers inhibit the pain pathways.
So when we come to tinnitus, as we begin to lose inputs that are delivered by the cognitive nerve fibers that tell us about sound, then conceivably the Type II neurons which we have been studying, which we think may be analogous to pain fibers, begin to gain more or stronger access to parts of the nervous system which are going to mediate sensations of pain and the kinds of behaviors that mean withdrawal or aversion."
https://www.kpwashingtonresearch.or...kpwhri-3-heal-grants-totaling-over-15-million
15 million went to CBT (in this case), only 1 million went to WinSanTor a company focused on reversing peripheral neuropathy.
I don't think there is anything directly targeting noxacusis. (noise induced pain)
If Nav 1.7 inhibitors can cross the blood labyrinth barrier they would extremely effective for all pain. People who genetically can't stimulate Nav 1.7 receptors, can't experience any pain anywhere in the body.
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