Noise-Induced Hearing Loss Alters KCC2 and GABA Inhibition in the Auditory Centers

[gameover]

You/us should wait for this Phase 1 to pop up. They will be looking for healthy
volunteers for the Phase 1.

I contacted them about volunteering for Phase 1. I got no response.

 

[Nick47]

I contacted them about volunteering for Phase 1. I got no response.

It doesn't matter. I love proactivity, my friend!

 

[BB23]

Well, here's some more productivity with no results.

I tried to reach out to the CEOs of Axonis, a married couple originally from Poland. I sent them emails to their personal addresses, reached out to them on Facebook, and even sent one of them a message on WhatsApp.

I haven't received a response or read receipts. It's been a long time since I did this. I'll update you if they respond.

I fear this company might not be able to deliver in the long run since its operating income is very low. I hate to see it run out of money mid-trials.

Let's see what happens with the trials this year, see if they are as legit as they sound.

I believe the bigger player here is Ovid Therapeutics and their product OV-350 since they are working with AstraZeneca, which means better chances of it coming out and being available worldwide.

They already have presentations for their investors as well. The slides are available online.

I'll send them a few emails as well.

I believe this will be a go-to treatment for tinnitus when it comes out in 10-15 years, but to make sure, let's wait until Axonis announces its trials if they ever do, and see if anyone reports improvements in their tinnitus levels.

 

[ajc]

I tried to reach out to the CEOs of Axonis, a married couple originally from Poland. I sent them emails to their personal addresses, reached out to them on Facebook, and even sent one of them a message on WhatsApp.

You clearly took it too far. Reaching out to personal email addresses, Facebook profiles, and Whatsapp is going into the stalking territory.

 

[Utdmad89]

I believe this will be a go-to treatment for tinnitus when it comes out in 10-15 years, but to make sure, let's wait until Axonis announces its trials if they ever do, and see if anyone reports improvements in their tinnitus levels.

10-15 years time

 

[Nick47]

believe this will be a go-to treatment for tinnitus when it comes out in 10-15 years,

It's not worth worrying about. By then, several treatments will be available. There will probably be 2-3 treatments and at least 1 objective test by 2028-2029.

 

[ploughna]

I believe this will be a go-to treatment for tinnitus when it comes out in 10-15 years, but to make sure, let's wait until Axonis announces its trials if they ever do, and see if anyone reports improvements in their tinnitus levels.

Looking at their website, they've listed 25 potential disorders that their KCC2 development might address, but no mention of tinnitus

Another case of off-label experimentation if it ever comes to market?

 

[Nick47]

I see Serotonin 5-Ht2a directly influences KCC2:

In healthy adults, activation of γ-aminobutyric acid (GABA)A and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl–]i), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), EIPSP, in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT2A receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT2AR agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).

→ Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

 

[BB23]

Tinnitus and visual snow syndrome coexist in some people with autism. Some of us here and on other tinnitus/visual snow syndrome forums already have autism/Asperger's. My theory is that most people who have chronic tinnitus and/or visual snow had faulty KCC2 channels from the get-go and maybe had undiagnosed neurological conditions, such as high-functioning autism, as I do, making them susceptible to conditions like tinnitus. I never realized it, to be honest. My friends did, though; in certain subjects, I excel beyond my peers but fail in other situations, mainly in social settings, etc. But keep in mind this is the personal conclusion that I have reached; nothing has been proven yet.

• Therapeutic potential for KCC2-targeted neurological diseases
• Regulation of KCC2 as a target for the treatment of autism

 

[BB23]

Something interesting I noticed from Arnaud Norena's paper:

These studies suggest that the mechanisms of GABAergic homeostatic plasticity involve not only the secretion of GABA or the GABA receptors, but also the KCC2, which eventually "decides" if GABA is inhibitory or excitatory.

The picture down below is from the OV350 website, presenting what is written above.

This could be why some people get tinnitus or have their tinnitus negatively affected by benzos such as Clonazepam.

There is a drug called CLP290, which is a KCC2 enhancer.

They can actually run a test using CLP290 on animals to see if the behavioral evidence for tinnitus improves or not and develop proper pharmaceutical treatments based on the results.

I'll even fund it if I survive a few years of this hell. I believe this can work, but we need someone to conduct proper tests and let the public know about the results. Please...