Can Blocking HCN2 Ion Channels Silence Tinnitus? RNID Funds Prof. McNaughton's Team to Find Out

RNID is funding a project at King’s College London and the University of Nottingham to test if it is possible to lessen or even silence tinnitus, by blocking the activity of an ion channel associated with chronic pain.

→ RNID: Chronic pain – how it might help us find a treatment for tinnitus
→ Academic profile of Prof. McNaughton
→ Publications by Prof. McNaughton

 

Very good find bro, I love hearing stuff like this I just hope it doesn't take a decade for human trials.

And wasn't this experiment done before?

 

@KoolKat, this research started about 3 years ago. It's in animal stage as far as I'm aware.

 

Just wondering, is there anything new on this?

 

"Professor McNaughton’s team, working with experts in tinnitus at the University of Nottingham, will test the effectiveness of different drugs that block HCN2 channels in reducing tinnitus in animals. This work is being supported by one of our Translational Research Grants."​

Looks like pre-clinical stage. There are a couple of papers published by him this year on pain and migraine but no human studies.

 

I got an answer from Professor McNaughton:

"Thank you for contacting me. Our work has shown that tinnitus is driven by the HCN2 isoform (protein conformation) – but unfortunately the HCN4 isoform is critical for a normal heart rate. What we need is to develop a drug that can distinguish between these two closely related forms of the protein. Will this be possible? It’s not yet clear, and so a practical drug that can be used in the clinic is some distance away.

Sorry not to be able to be more optimistic. [...]"​

 

So is he confirming HCN2 Isoform is responsible for all this madness?

Or, because there have been no human clinical trials, this, like all the rest, is just a theory...

 

Sorry, but can someone explain if this is related to potassium channels and if this all ties into the Dr. Susan Shore's theory?

 

There isn't much relation of KCNQ2/KCNQ3 potassium channels to Dr. Shore, other than her briefly going over that information in her papers, and both potential treatments being related to the Dorsal Cochlear Nucleus.

 

So basically this is good news as there is now a prominent hypothesis/theory that’s finally agreed upon as a potential treatment if I’m looking at it in a positive light?

 

You can't say that they are exactly the same. The Susan Shore device has a very large impact on stimulating the somatic systems, so to speak (trigeminal nerve, etc), not only the DCN. I can't say they are exactly the same. But certainly Susan's profound success is a positive indicator for this potential potassium channel treatment.

 

After some research into this, there's already a drug that blocks this particular channel, called Ivabradine. It's used for POTS which I and many other people have after getting COVID-19. There is one single anecdote of it stopping someone's tinnitus:

"Yes, it definitely has. These are the improvements that I have noticed:

• NO FAINTING EPISODES!
• No more tinnitus
• No more tremors
• Drastically reduced dizziness and brain fog
• Reduced fatigue
• Reduced blurry vision and hearing/visual disturbances
• Reduced breathlessness and palpitations
• Reduced nausea
• Better memory and concentration
• Dramatically reduced exercise and heat intolerance
• Less problems with reduced sweating
• Fewer issues with cold extremities and blood pooling
• Fewer low moods (I would not say I felt depressed but I did find myself feeling overwhelmed and down at times)
• Better sleep and fewer nightmares"

Source: https://liveyourselfbetter.wordpres...-beta-blockers-ivabradine-and-a-happy-ending/

 

While this does show promise, further research needs to be conducted. One thing that makes someone better can make another worse.

 

I'm going to try Ivabradine. Off label. Fingers crossed, I'm going to be a guinea pig. I will try anything, I can't describe the suffering. I will keep you updated...

 

@Tomas80, sorry. I understand.

Did you try Latuda?

 

I got Ivabradine first. I'll try itfor a few weeks. I won't try Latuda, but when I finish Ivabradine, I will then try Reagila (Cariprazine).

 

I am diagnosed with POTS and have had it for several years, even before COVID-19. I’d absolutely try this medication if there’s a chance it could (safely) reduce my tinnitus. I’ll start researching it.

To be clear: Ivabradine blocks both HCN2 and HCN4? I’m not a biologist and don’t really understand how these channels work...

 

@chinup, HCN4 is to do with the heart. I think it slows it down. As you know, as soon as you stand up, you get tachycardia if you have POTS.

I saw this on Twitter:

"My tinnitus improved, not necessarily because of, but whilst taking, Ivabradine. My BP is low all the time. I had to stop taking all meds & supplements for a few days recently, & the tinnitus was back full-time, so *something* is making a difference to me."​

 

Does Latuda do it as well? My psych had suggested that.

 

@IndyMLVC, does Latuda do what? What are you asking?

 

Third day Ivabradine 5 mg daily. I just took my heart rate - 49.

OMG. I'm normally in the 70s to 90s due to stress and anxiety from the tinnitus. No change in tinnitus yet.

 

I'm asking what does Latuda do? Why was it brought up?

 

@IndyMLVC, it was brought up by 1 member who had significant success. It has a pharmacological profile that suggests it 'might' work for others too, based on antagonism of 5-HT receptors and dopamine agonists. Read the medication thread.

It's also relatively new to market.

 

I think Ivabradine is nonselective; it blocks all HCN's.

 

The smallest dose of Ivabradine is 5 mg. Even though I only took half of that, I still had pain in my heart. I had to stop taking it. I'm not going to risk my heart. The experiment did not bring success :/

 

I mean, I was just speculating, I don't think jumping on heart meds is smart. If you're really that desperate, Flexeril and Valium are two drugs that actually do give temporary relief, especially if you have somatic tinnitus.

 

Prof. McNaughton gave a recent interview to an online audiologist. He summarised tinnitus to chronic neuropathic pain, saying that tinnitus is peripheral in origin.

He was successfully able to eliminate behavioral evidence of tinnitus using a HCN2 blocker. The tinnitus suppression was temporary.

In theory this may equate to humans taking a drug twice a day to suppress tinnitus over a 24 hour period.

A little bit more:

You may be correct. I got in touch with Prof. Peter McNaughton regarding the HCN2 drug target that he is involved in developing. He also commented on the work of the Shore Lab.

 

@Nick47, very interesting.

I wonder if this could also be a treatment for noxacusis?

 

Yes, I think it's very plausible. As noxacusis is chronic for some, the alignment with chronic neuropathic (nerve) pain is strong. The fact it silences tinnitus in the animal studies is promising, although not all animal research translates to humans.

I would think noxacusis is also peripheral in generation if sound causes pain and therefore central gain/hyperacusis is no longer the cause.

They found evidence of the HCN2 protein in the spiral ganglion in the inner ear and they are sure that tinnitus elimination was not due to the drug's interaction on the brain as the drug is known to not be able to penetrate the blood brain barrier. In other words, the drug only acted on the peripheral nerves. These findings support a peripheral starting point of tinnitus generation that then alters the firing rate in the DCN.

So the issue going forward will be to raise significant funds to develop a more selective drug that does not interfere with HCN4. Big pharma would be ideal.

 

Did they try this on humans yet, or are these animal findings?

This looks to have crazy potential, I just hope it doesn't take them 20 years to get a move on. If Dr. Shore's device works, then I'm sure this is going to do something.