University of Birmingham — Identifying Cochlear Nucleus Drug Targets

[Nick47]

UK University. Basically the research team has identified that there is a loss of the inhibitory 5-HT1A receptors in the Cochlear Nucleus in tinnitus and are looking to develop a drug to target this.

→ Identification of a suitable drug target(s) to manipulate dysfunctional neuronal function in the cochlear nucleus to relieve noise-induced tinnitus; further studies following successful identification of the relevant neurones likely to be amenable to drug manipulation

Funding from → the Ministry of Defence.

What's interesting about the above research is the UK Government put this out to tender in the summer for £50,000 and it was through the Ministry of Defence department. It was subsequently awarded to Birmingham University.

 

[TashaJane]

@Nick47, interesting! Looks like the funding ends in September. I wonder if they got very far and what their plan is.

 

[Nick47]

@Nick47, interesting! Looks like the funding ends in September. I wonder if they got very far and what their plan is.

@TashaJane, I don't know. It seems to be unknown ongoing research. In fact it started over 10 years ago with some funding from the BTA.

 

[Jonno02]

Damn, £50k won't get them far. This would be a perfect cure.

 

[Joeseph Stope]

Damn, £50k won't get them far. This would be a perfect cure.

Yes, it seems when it comes to financing research, hearing related problems are not high up on the list.

I'm delighted that science has come up with some answer to sickle cell anemia, but hey... that isn't very prevalent around these parts of the world.

 

[Nick47]

Damn, £50k won't get them far. This would be a perfect cure.

You would think not. It's public money and the university are happy to agree. Makes you wonder about all this Hough Ear Institute bollocks and how they need half a billion.

 

[Fightthearmy]

You would think not. It's public money and the university are happy to agree. Makes you wonder about all this Hough Ear Institute bollocks and how they need half a billion.

And why on earth should you believe the clinical trials were to be successful and so firmly as to give them half a billion? Because 'they said it works'; you should take their word?

 

[Nick47]

Interestingly, when I brought this research up with Prof. Dirk De Ridder in February, he was not aware of it. His view was that some researchers operate on their own in an "ivory tower." He didn't think it would work as by targeting one type of neuron does not fit in. I don't know.

Is it worth emailing the researcher? It looks like the funding to September 2023 was to develop the drug. After that, is it animal testing or human trials?

 

[ImmortalWombat]

Any update on this?

 

[StoneInFocus]

UK University. Basically the research team has identified that there is a loss of the inhibitory 5-HT1A receptors in the Cochlear Nucleus in tinnitus and are looking to develop a drug to target this.

"The team will study these 5-HT1A-deplete neurones using cutting edge research techniques to identify suitable drug targets that when engaged by suitable drugs will deliver inhibitory signals to these neurones to replicate the function of the lost inhibitory 5-HT1A receptors."

I don't know to what extent these 5-HT1A receptors have disappeared from CN neurons, but if there are a few of them left, would just raising the amount of 5-HT1A agonists in the blood to compensate for their loss work?

Could ]Urapidil, an α1-adrenoceptor antagonist and an 5-HT1A receptor agonist, achieve the same effect? I think it could go both ways as vasodilators also seem to exacerbate tinnitus for some people.

The effects of regular SSRIs on tinnitus seem very mixed, but of course they affect other serotonin receptors as well.

 

[Josh59]

It looks like the funding to September 2023 was to develop the drug. After that, is it animal testing or human trials?

Do you have any news on this?

How many years will this research programme last?

 

[BB23]

What's the current status of this research and drug?

 

[Nick47]

What's the current status of this research and drug?

I have no idea.

 

[dd314]

"The team will study these 5-HT1A-deplete neurones using cutting edge research techniques to identify suitable drug targets that when engaged by suitable drugs will deliver inhibitory signals to these neurones to replicate the function of the lost inhibitory 5-HT1A receptors."

I don't know to what extent these 5-HT1A receptors have disappeared from CN neurons, but if there are a few of them left, would just raising the amount of 5-HT1A agonists in the blood to compensate for their loss work?

Could ]Urapidil, an α1-adrenoceptor antagonist and an 5-HT1A receptor agonist, achieve the same effect? I think it could go both ways as vasodilators also seem to exacerbate tinnitus for some people.

The effects of regular SSRIs on tinnitus seem very mixed, but of course they affect other serotonin receptors as well.

Some cannabinoids are also modulators of 5-HT1a. This is 100% anecdotal on my part, but CBD (5-HT1A agonist) tends to make my tinnitus worse than CBG (5-HT1A antagonist).

 

[Nick47]

It would be good to find out where they are in this research. However, I don't know how to contact him.

 

[ajc]

It would be good to find out where they are in this research. However, I don't know how to contact him.

It seems to have finished. You could email n.m.barnes@bham.ac.uk and ask him for an update.

 

[Nick47]

You could email n.m.barnes@bham.ac.uk and ask him for an update.

Done!

 

[Joeseph Stope]

Great work, @Nick47, on keeping these ideas alive. Your article may make someone in audiology research curious.

The only thing left to do is find the stray millionaire who will help keep the research alive and active.

 

[Nick47]

The only thing left to do is find the stray millionaire who will help keep the research alive and active.

Ten humans taking a pill can be done in a single center by a handful of postgrads. No need for millions of pounds. All bullshit.

 

[ajc]

Ten humans taking a pill can be done in a single center by a handful of post-grads. No need for millions of pounds. All bullshit.

The issue is that in the US at least post-grads are often paid approximately $70-90k/year, with a 1-year contract often desired at a minimum, and a multi-year one preferred.

If you have, let's say five post-grads working on a project, their salaries + other admin and lab costs do add up. Not to the degree of millions but easily above $500k and closing in on the million.

How much are post-grads paid in the UK?

 

[Nick47]

How much are post-grads paid in the UK?

About £20,000 in the UK, which is about $26,000.

 

[Joeseph Stope]

My scant knowledge of the human trials side of the bio-pharma bizz was that the volunteers were very often, or maybe you could say, usually out-of-work, down-and-out-young males with a drinking problem. It was necessary to pay them above the industrial wage and provide accommodation and board... otherwise, they'd head for the nearest pub and drink all night -- which might interfere with the efficacy or non-efficacy of the candidate drug.

These are just my laid-back observations. I never participated, and I was warned by a medic to steer well clear as, say, for instance, a new candidate drug for, let's say, rheumatism was being trialed -- the after-effects could come years later. So the costs are in there somewhere.

 

[JimmyStrong]

a new candidate drug for, let's say, rheumatism was being trialed -- the after-effects could come years later. So the costs are in there somewhere.

If that is the case, does it mean if a drug for tinnitus/hyperacusis was created right now, it could only be available 10+ years from now, so that scientists can monitor for any side effects?

 

[Joeseph Stope]

If that is the case, does it mean if a drug for tinnitus/hyperacusis was created right now, it could only be available 10+ years from now, so that scientists can monitor for any side effects?

The point I was emphasizing is that conducting trials requires both time and money.

The initial stage involves scientists and medics creating a computer graphic design of the proposed molecule, illustrating how it is supposed to interact with the body to achieve the desired effect. Next, they might test it in a petri dish or test tube.

Following this, animal trials are conducted using guinea pigs, lab rats, and similar subjects. If these trials indicate that the molecule is safe, human trials are the next step. A selection of healthy, usually young, volunteers are chosen to observe the effects on humans, primarily to ensure the drug's safety. These are the volunteers I mentioned in my previous post.

Once the pharmaceutical is deemed safe, the next stage is to prove its efficacy or to confirm it is as effective as existing treatments. For this trial, people who actually suffer from the ailment—in our case, tinnitus or chronic tinnitus—are needed. Currently, there are limited treatments available, mostly cognitive behavioral therapy and similar approaches.

Even after a drug reaches the market, practicing doctors remain vigilant to detect side effects and long-term effects.

Regarding your question about the availability of treatments within the next ten years, there are indeed a number of drugs and therapies in the pipeline, some expected as early as this year or the next. While success has been limited so far, there have been a few exceptions.

Who knows? Every so often, a breakthrough occurs in medicine. So, we continue to stay tuned to Tinnitus Talk to keep updated on the latest developments.