Medical Advancements

Starting a thread for anyone who is interested in following medical progress in general and not just in the otology and tinnitus space. It's definitely a transformative time for medicine where research is moving away from symptomatic treatment and addressing the underlying pathophysiology.

I thought it would be neat to put groundbreaking research, drug trials and new therapy releases etc into one place.

I will start with two I read today:

Long term treatment for blood disorders such as sickle cell through gene editing (blood transfusions no longer needed):

Preliminary but ‘nothing short of great.’ New data on CRISPR treatment for blood diseases suggest cure is possible

This next one is very preliminary and on mice only thus far but it describes using a viral vectored approach to epigenetically affect genes to self repair cranial nerves, such as the optic nerve on their own:

Reversal of biological clock restores vision in old mice

 

The recent breakthrough in AI (DeepMind) in determining protein structures seems worthy of a mention. From what I have read, it definitely appears to be a real credible 'breakthrough' and something that was not expected to be achieved for decades.

‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures

 

AlphaFold seems to be great in determining the final structure of a protein, but not how it folds and gets there. There's still a bunch of work to be done there. It's also a shame that this is owned by a private company and not open for everyone to use.

Folding@Home is doing just that, I can encourage everyone to download it. They're currently simulating potassium ion channels, which are actually likely connected to tinnitus if Thanos Tzounopoulos is correct.

 

This is very uplifting. One of the first ever patients to receive CRISPR for sickle cell disease is thriving a year on!

1st Patients To Get CRISPR Gene-Editing Treatment Continue To Thrive

Honestly, this stuff is so heartwarming and encouraging to hear.

 

PRAX-944 is a T type calcium channel blocker being developed by Praxis Precision Medicines for essential tremor (ET). It's currently in phase II with proof of concept results expected soon and phase III trials expected to start sometime in 2021, meaning it could hit the market sometime between 2023-2024.

https://praxismedicines.com/
https://adisinsight.springer.com/drugs/800052234

 

Article from The Alliance for Regenerative Medicine on how their work and how COVID-19 has affected them.

Regenerative medicine in the era of COVID-19

 

Encouraging news! I read an article recently about the development of eye drops that can change the shape of the eye to correct the need for reading glasses as we age. As someone who needs both contacts and glasses for reading this is very helpful!

 

to twa:

Most definitely it seems that barometric and other weather changes significantly affect tinnitus (as well as migraines and arthritis). In fact, my neurologist said that it is established that weather changes can trigger migraines.

I am looking into anti-inflammatories under the theory that various organs and tissues are swollen because of these changes (and perhaps such altering inhibits their full functioning).

 

Scientists of the University of California identified a drug to remyelinate nerves. They used it on mice with multiple sclerosis to remyelinate the optic nerve to restore vision. The improvement is reported to be about 50%.

Remyelinating drug could improve vision in patients with multiple sclerosis

This drug might be interesting for treating pain hyperacusis if it is caused by demyelinated nerves (@Contrast has come up with the theory that demyelination might be a possible cause for pain hyperacusis).

Edit: Actually it depends. The body can to some extent remyelinate nerves but based on my research it doesn't work for all nerves (p.e. optic nerve). So in order for this drug to work for pain hyperacusis the repair mechanism would have to fail.

 

Here is a link to an interview (not in an academic setting) of one of the scientists working on the "reversal of the biological clock". I found it very informative and it will allow a deeper understanding of what is talked about in the paper @FGG shared with us.

This Harvard Professor Explains the Secret to...

 

Frequency Therapeutics is doing something similar:

Frequency Therapeutics: Our Program for Multiple Sclerosis

 

Are you a doctor?

 

Yes but for animals .

 

This is neat. AI discovers new drug for pulmonary fibrosis:

Breaking Big Pharma's AI barrier: Insilico Medicine uncovers novel target, new drug for pulmonary fibrosis in 18 months

 

I've been delving into this topic extensively over the past few weeks. Researchers are currently working on a nanoparticle antibiotic treatment for cases of recurrent/chronic UTIs. This would eliminate the need to rely on protracted courses of oral antibiotics to treat this effectively.

There has been a company that has been set up with the hope of commercialising this called Atocap, using Nitrofurantoin. One thing I wonder is what is the protocol for clinical trials when the drug itself has been approved and used for decades, but it is mostly the delivery method that is novel. Would that streamline/speed up clinical trials?

Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection

 

Are they implanting the particles or is this an oral drug? Because if it's implantable biodegradable antibiotic beads, vets have been doing this for drug resistant abscesses in rabbits for literally decades.

 

They are using PLGA (poly-lactic-co-glycolic acid) particles loaded with an antibiotic directly into the bladder. So, it would be implanted.

Just been skimming through the paper again and I think the key thing with this is that it is able to target bacterial reservoirs that have become embedded deep within the bladder wall, so it is a more powerful and targeted approach.

 

Then it's exactly the same as what vets have done with rabbits for years. And yes, it works when nothing else will (rabbits get some pretty resistant infections).

 

Btw, @serendipity1996, some compounding pharmacies make these for vets (and before that, vets used to make it themselves on site). So I would only think a clinical trial would need to happen if doctors only felt comfortable using a commercially available product or if they think humans might react differently (it's possible).

 

This one’s kinda cool.

Sorrento Therapeutics - RTX (resiniferatoxin)

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

Resiniferatoxin: Using Extreme “Heat” to Treat Pain

 

@FGG, this paper goes into more detail on the science behind Nav 1.7 CRISPR therapies for pain relief. Very cool how they have managed to come up with a way to 'repress' the Nav 1.7 gene instead of permanently editing it as obviously it wouldn't be beneficial to eliminate pain perception entirely.

Long-lasting Analgesia via Targeted in vivo Epigenetic Repression of Nav1.7

One of the authors, Ana Morena, founded Navega Therapeutics in 2018 too.

 

@FGG at the end of this article it states that they expect to reach clinical trials in 2 years

Gene Therapy Might One Day Treat Chronic Pain

 

Anyone here know of the VivAer nasal passage way remodeling? I have a deviated septum and I'm not too keen to rush into a septoplasty, I wanted to see if anyone here was familiar with this or if it's quack technology.

 

Encouraging news. The NHS has just approved a gene therapy treatment, Zolgensma for Spinal Muscular Atrophy.

The UK’s National Health Service just approved a drug that costs nearly $2.5 million a dose

 

I was about to ask if this med working on NaV1.7 could possibly be given on a "compassionate use" basis. It seems so promising, to me, to treat noxacusis.

From Wikipedia:

Nav1.7 is a sodium ion channel that in humans is encoded by the SCN9A gene. It is usually expressed at high levels in two types of neurons: the nociceptive (pain) neurons at dorsal root ganglion (DRG) and trigeminal ganglion and sympathetic ganglion neurons, which are part of the autonomic (involuntary) nervous system.​

But I see now that this drug is not even tested on humans yet and that we are far away from any talk about compassionate use I guess. What a shame.

I´m having a ganglion stellatum nerve blockade on Monday, but that will only work if the trigeminal nerve is involved with the pain. I´ll tell you if it did anything in the proper thread for it.

@FGG, @100Hz and @Zugzug:

Not to disregard anyone else, but from reading different threads it seems at least us four suffer with noxacusis in the extreme.

I can only speak for myself, but it kills me every second of the day. There does not need to even be sound present. Just knowing I will at some point through the day be exposed to some kind of sound makes me on high alert every second of the day. High frequency noise cancellation does not really cut it. Industrial hearing clocks makes me feel so damn isolated and put pressure on my ears.

You guys seem so highly intelligent to me. Have you not found anything to help ease your pain, except for probably benzos?

@FGG, do you think there are any present meds that act on the NaV1.7 channel? Like any of the antiepileptic drugs for instance?

It is just crazy that there are so many interesting drugs in development, but they seem to never develop from that status. It is like time has come to a halt. It is Twilight Zone and Groundhog Day at once having this condition.

I just wish we all could find a way to ease the pain.

 

As far as I know, there aren't any current drugs available that act on these channels.

@serendipity1996 would be another person to ask.

There have been companies (Biogen for one) that have tried but pulled out because the drugs weren't specific enough and there was activity at other related ion channels (the Trobalt problem, basically).

You can still get a lab to make some of these compounds but I really wouldn't go that route, personally, as there was obviously reasons to abandon the drug (it's also less effective when the drug is less selective, too, in addition to more side effects).

This company has a different approach though:

https://navegatx.com/en

They are using epigenetics to switch on/off the receptor and it has a lot more specificity. Maybe you could contact them and ask about trials (I think it would be too early for compassionate use, I think you might have to have done a Phase 1 first).

Here is their recently published paper:
https://stm.sciencemag.org/content/13/584/eaay9056

I wouldn't say my noxacusis is extreme. The pain is persistent but more moderate but one thing that does help me is lots of liquid Magnesium chloride (the oral formulation, not the topical).

If I recall correctly (could be thinking of someone else), you were weaning off of Benzos. Make sure you get a specialist to help with that, if so (i.e. someone familiar with the Ashton protocol). People tend to get better otologic symptoms once that nightmare is better.

 

Thanks for tagging me, as I hope you can find some relief. Unfortunately, I don't have noxacusis, but really severe and progressive loudness hyperacusis. I am less knowledgeable than many of the others with noxacusis.

I wonder if you have tried Gabapentin or Pregabalin. The antidepressant Cymbalta is also prescribed for diabetic neuropathy sometimes. I want to say @linearb has managed with some combination of Gabapentin and Benzos.

I haven't followed NaV1.7 blockers too closely, but if there's a way to obtain compassionate use, I'm sure there are plenty of users on here who would be interested.

I'm sorry you are experiencing horrific noxacusis pain.

 

I should add too, @grate_biff, that there have been completely unverified rumors that Ebselen has helped (someone posted a friend of a friend anecdote) and that might be easier to obtain (see the Sound Pharmaceuticals thread) from a lab if the situation is dire and it's possible the company may even be open to Compassionate Use (something to definitely ask them on the upcoming Tinnitus Talk Podcast).

 

Thank you both for responding.

Thank you. I will contact them for sure as I will with the CRISPR people. I guess it all comes down to the SCN9A gene. How I wish I was one of those who had this gene switched off by birth. I'll happily be the first human they test it on.

Yeah, that's me! It's never ending. I recently lasted 10 months without it, but I cracked in the end partly because of some bad advice and the severity of my noxacusis. I really think you are right about that once the withdrawals are better, my ears will as well. That's probably why GABA drugs like benzos and Baclofen gives me far more relief than opioids. It's strange though as I have read a lot about GABA, NMDA-receptors the GABAeric and Glutamate system. And there is not much literature about how it affects pain, but I guess if I google it I will learn more. I guess when we talk about inhibition and excitatory effects at cellular level it affects pain signals as much as anxiety and anxiolytic effects.

I have been in many encounters with people regarding my benzo troubles. I will have to teach them about Heather Ashton's research every time.

I have tried both Gabapentin and Pregabalin with no real effect, just lots of side effects. I'm already on two different AD's so I'm reluctant to try another at this point.

Thank you!

I'll try and contact them, and see what they say!

You are both a real asset to this forum. I'm in awe over your analysis on the Frequency Therapeutics thread.

Keep it going!

 

Is this available OTC in your country:

https://en.wikipedia.org/wiki/Ambroxol

They are starting to test it for Fibromyalgia (which I think has some definite parallels with noxacusis) and other chronic pain and it reportedly works better than Gabapentin.

Seems overall safe short term (and has effects on a similar channel to Nav1.7, namely, Nav1.8) but warning there have been zero long term studies that I can find.

This is total Guinea Pig stuff but I like to post any possible lead with that caveat.

Also tagging @serendipity1996, @Aaron91 and @100Hz.

Side note, it does seem to have some intracellular calcium releasing effects and there was some talk recently about calcium channels and noxacusis but I am not sure if this would have an effect or not. My gut tells me it would not since calcium channel blockers help with Fibromyalgia pain apparently but this reportedly helps more.