Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate

Discussion in 'Research News' started by d'Wooluf, Jul 14, 2020.

    1. d'Wooluf

      d'Wooluf Member

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    2. FGG
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      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

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      Interesting find but the drug was given extremely acutely (24 hours).

      These drugs (biphosphantes) do have their own risks (e.g. osteonecrosis of the jaw).

      I think I prefer local administration to systemic given that concentrations need to be very high to reach the cochlea unless the drug is extremely safe (e.g. Hough pill, reportedly).
       
    3. tommyd87

      tommyd87 Member

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    4. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      True, but they say:

      'Our results have transformative translational implications for hearing loss and suggest that zoledronate could be repurposed for the treatment of SNHL with cochlear neuropathy and associated compromised ability to understand words in noise, tinnitus, and hyperacusis. There is potentially a long therapeutic window because cell bodies of SGNs can survive for many months (in animal models) and years (in humans) after peripheral synaptic and neurite loss (Liberman and Kujawa, 2017).'
      They do say that further research is required to determine- amongst other things- most effective mode of administration. I prefer intra-tympanic injection as well, but I also prefer the treatment mode that is actually accessible. I do have concerns about the capacity of the health system to deliver IT injections to large swathes of the population when effective treatments are finally approved.
       
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    5. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      I really don't have the understanding required. Sorry. There are people here with better knowledge of the inner ear who may attempt it. I'd probably appreciate that as well.
       
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    6. tommyd87

      tommyd87 Member

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      In Australia am actually sure that this wouldn't be a problem per say because they often authorise and train other staff members like nurses who operate in a practice to do this. Otherwise it will be done through the GP rather than the ENT. There is really rarely a problem with this and it will allow treatment to proceed pretty quickly.

      Alternatively a system may be set up where they run a practice and have an ENT supervising it.

      Obviously you are from another country to me so I am not sure what your rules are as I don't know where you are based.
       
    7. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      Funnily enough, I'm not. I'm in Perth. I was under the impression that it had to be done be an ENT. I mainly got that impression from reading this forum. If what you say is true, that's great.
       
    8. FGG
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      This wouldn't likely be a problem in the US either. Any Otologist and any ENT that treats a lot of Meniere's patients already does this procedure here.
       
    9. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      It it's *only* Otologists and ENTs (i.e. the specialists themselves - not their staff) that do this procedure, then we have a problem. That's my point.

      @tommyd87 says that GPs and nurses can do it. Is this for sure?
       
    10. FGG
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      It's a very short procedure, though.

      Only ophthalmologists perform LASIK eye surgery (which takes a lot more time and equipment as well) and between 700,000 and 1.4 million of these are done per year.

      Edit: the best way to minimize your wait time when regenerative therapies are released is to already be an established patient somewhere that does these procedures routinely. At least in the US, the long wait times are usually for new patients.
       
    11. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      The procedure may be short, but it's not as if you can walk up to the reception desk and just order it. Someone has to assess it as appropriate for your medical history and current symptoms. Presumably that would be the ENT.
      That's been around for a while I think. Numbers swell to meet demand. I would guess there are many more ophthalmologists now than there were pre-laser eye surgery (talking without any real knowledge here). According to https://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing, about 28.8 million Americans could benefit from wearing hearing aids. Say that about 20 million of those could benefit from regeneration therapy, that's still a lot of people waiting in line for treatment when it becomes available.

      I think we have to hope that GPs and nurses can be trained in and allowed to perform the procedure.
       
    12. FGG
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      I wouldn't want a newly trained in IT injections GP to do the procedure on me personally because of the risk of ear drum rupture (which could make tinnitus worsen). But everyone has their own cost/benefit to weigh there I suppose.

      I got LASIK done in 2002 (so fairly early) and there were only two doctors in my area who did it at the time. The one I went to had Sunday hours just for the procedure and I only had to wait about 2 weeks for the appointment. At the time I remember him saying he had done the second most in the country next to an ophthalmologist in Orlando, though but any ENT who had "Sunday hours" just for the procedure fit an extra 24 patients a week for this.
       
    13. tommyd87

      tommyd87 Member

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      It wouldn't surprise me if in Australia a practice was simply set up to do this treatment as am sure a specialist would happily take the consultation cost of $120 to do it. it would not shock me if this gets offered out of our specialist ear and eye hospital as the government possibly will consider subsidizing this for some people like they do now for cochlear implants. It is quite possible that the cost would end up being basically substantially cheaper which would justify it being subsidized.
       
    14. tommyd87

      tommyd87 Member

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      In Melbourne most LASIK is conducted in specialist surgeries so the doctors who do them often focus running their practice for this and not other procedures. Then there are other ophthalmologists obviously who deal with other procedures.

      Potentially any ENT could commence this treatment though I think that this would get left to otolaryngologists or ENTs who are general but cover a lot of nose stuff.
       
    15. AUTHOR
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      d'Wooluf

      d'Wooluf Member

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      Agreed on that one. Actually, a nurse working within an ENT practice and trained by the ENT with the ENT available in case of trouble I might accept. I'm not sure that would be acceptable to a whole bunch of other people however. Medical insurance companies for instance.
      Sure. I don't know many would want to do that and only that. To them it would be a bit like shelling prawns (shrimp) all day.
       
    16. tommyd87

      tommyd87 Member

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      Somewhat likely that ENTs will work with this though because by doing it, it will end up being a big earner for them due to the fact that they will make a lot of money for what will be a short simple visit. Pretty positive that they can charge Medicare for the injection in addition to a visit. So this therefore could mean that if they were just seeing you to deliver the dose that would likely be upwards of $200 for a potential 5 minute visit. This is in conjunction to the other obvious times they might need to see you.

      Then if you need 5 doses plus an initial and a couple of follow-up consultation visits. Very quickly this becomes $1500 approximately for the treatment. An excellent return for a fairly simple procedure. I'm positive that this would not be done as a sole specialty however, it would be done in conjunction with whatever additional other areas of work or treatment they do. It would not be bad for maybe no more than two hours of work and a much less laborious or risky type of treatment compared to just say doing actual surgeries.
       
    17. Sloth
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      Isn't that a bit optimistic? I think I heard somewhere that in the trials they had to lie on their side for 30 minutes.
       
    18. tommyd87

      tommyd87 Member

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      Probably actually accurate although I really think that the ENT would leave you post the jab and allow someone like a nurse to supervise. Then they shall return to check at the end if needed. This currently happens here now with many current vaccines and other treatments done via injections. There doesn't appear to be a need for the ENT to supervise the whole procedure.
       
    19. Jurger

      Jurger Member

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      I’ve had 4 intratympanic injections. The injection itself takes 2 minutes. The entire procedure is not that short though, but still doable. First off it takes about 15 minutes to anesthetize the eardrum. Then they do the injection. Then you lie down for 30 minutes so the drug can permeate through the RWM. Since application is close to your vestibular, you’re usually pretty dizzy and shouldn’t drive home yourself. Dizziness got better with me after every injection (was hardly dizzy the fourth time) though. All in all, it’s not as short and less of a hassle than drug companies make it out to be.
       
    20. Jurger

      Jurger Member

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      I found this from the study particularly interesting:

      The finding that zoledronate regenerates cochlear synapses may explain previous reports that show that zoledronate improved or stabilized progressive SNHL in patients with otosclerosis.

      If this is true, then off-label use of this drug for hearing loss should now be on the table for those patients where the benefits outweigh the risks.
       
    21. FGG
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      It's short for the doctor at least and that's likely to be the bottleneck in most practices (unless they are short on support staff).
       
    22. tommyd87

      tommyd87 Member

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      that would be fantastic if that does happen as provided it is safe to use. it also again supports the otger research
       
    23. tommyd87

      tommyd87 Member

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      You could run an in-patient session where you did like five at a time by simply lining them up lol and treating them one after the other. Maximum money for maximum treatment. The doctor doesn't have to then spend all day doing this, the patients get treated and everybody goes home happy.
       
    24. Jurger

      Jurger Member

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      Only way is to ask your ENT for a standard dosage of zoledronate. Apparently that’s what’s shown results for patients.
       
    25. tommyd87

      tommyd87 Member

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      Do you mean outside of obviously allowing this to be used as a mainstream treatment? I reckon I have got no chance of that happening. They will look at me madly.
       
    26. FGG
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      I also think if it worked at the standard doses this would be more widely known as these drugs are not uncommonly prescribed to older people.
       
    27. Jurger

      Jurger Member

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      Yes, that’s what off-label use is by definition.
       
    28. Jurger

      Jurger Member

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      Doesn’t hurt to try given the lack of options for hearing loss out there. Provided the possible improvements outweigh the side effects. Who knows how many of the old people that are taking this drug are getting their hearing checked regularly. Lack of testing is one of the big issues in hearing health care isn’t it?
       
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    29. tommyd87

      tommyd87 Member

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      When you say if it worked at the standard doses, do you mean in order to treat tinnitus? Like I could obtain a dose to use for this purpose?

      ENTs don't know much about allowing this for tinnitus treatment.
       
    30. FGG
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      It looks like (at least from this patent) that a higher dose (the one used for otosclerosis patients vs Osteoporosis patients) is used:

      https://patents.google.com/patent/US7781419B2/en

      This article was posted on another thread which suggests that it is the otosclerosis dose is used:

      https://medicalxpress.com/news/2020-07-bone-disease-medications-reverse-loss.html

      The normal dose "osteoporosis" dose for Risedronate, for instance is 35mg a week.

      I do wonder about an increase in the more serious side effects of that class of drugs at that dose (e.g. osteonecrosis of the jaw) which is at least rare at standard doses but maybe they have that data based on people treated for otosclerosis.
       
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