Cx26 Gene Causes Hyperacusis-Like Hearing Oversensitivity and Increase Susceptibility to Noise

[Lucifer]

→ Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise

I've read this article but I'm having trouble with understanding the terminology in this. I thought someone else could explain it to me.

They talk about GJB2 (Cx26) mutations. I'm not sure if this article is saying reducing GJB2 (Cx26) will reduce hyperacusis & susceptibility to noise, or the other way around, or something else I'm not understanding.

Maybe someone like @Nick47, @Diesel or @Chad Lawton could have a read through it.

 

[lymebite]

My understanding is that the article is saying that if you have the mutation of that gene then you are extra susceptible to developing hyperacusis.

The only way to know if you have the gene mutation is to get your DNA sequenced from 23andMe or a similar company. You spit in a test tube, mail it back, and a few weeks later you get all of your DNA reports online, including whether or not you have one or more of the GJB2 mutations.

 

[Lucifer]

Thanks @lymebite. I didn't want to post another thread but have you had a look at this article:

Meet the Researcher: A talk with Megan Beers Wood, recipient of our Emerging Research Grant

They talk about CGRP-α cell-to-cell signal. They are looking at mice cochleae a day after noise exposure to see their inflammation status by looking at the number and shape of immune cells, and compare that with mice cochleae that have the CGRP-α cell-to-cell signal blocked by a drug.

What do they mean by "drug" when talking about CGRP-α cell-to-cell signal blocked by a drug? Are they testing to see if this drug can reduce hyperacusis and susceptibility to noise?

 

[Nick47]

Yep, if you have the Cx26 gene, you are more likely to get hyperacusis.

 

[lymebite]

@Lucifer, I don't know what CGRP med(s) the mice are receiving, but I did hear of a human hyperacusis patient who has tried two different CGRP meds for hyperacusis, Emgality and Nurtec, though I don't know anything about their experience with them. I wonder if anyone else has tried CGRP meds. I don't recall anyone posting here about trying CGRP meds for hyperacusis, I wonder if they could be helpful.

 

[lymebite]

Poster at ARO this week.

 

[Shizune]

My understanding is that the article is saying that if you have the mutation of that gene then you are extra susceptible to developing hyperacusis.

The only way to know if you have the gene mutation is to get your DNA sequenced from 23andMe or a similar company. You spit in a test tube, mail it back, and a few weeks later you get all of your DNA reports online, including whether or not you have one or more of the GJB2 mutations.

Have you had your DNA tested through 23andMe and did it show any specifics? I got myself tested through a similar website and it offered me none of this information. I just read that such websites don't fully give you all your genetic info, and you might need to get a doctor ordered one. Just want to clarify.

I got another DNA test done through my doctor to see what medications may work best for me, still awaiting results but I'm curious now if it can detect any of this.

I'm excited hyperacusis research is making some strides here.

 

[lymebite]

Have you had your DNA tested through 23andMe and did it show any specifics?

Yes, I had my DNA tested in 2015 through 23andMe on what they call their V4 chip. The V4 chip tests for 2 of the 8 mutations on the hyperacusis gene. The V4 chip was upgraded to the V5 chip in June 2020. The new V5 chip tests for all 8 of the hyperacusis gene mutations. So anyone who had it done with 23andMe after June 2020 can check their report for all 8 mutations of the hyperacusis gene.

I am upgrading my chip from V4 to V5. 23andMe is charging me $125 for this upgrade. In practical terms, that "upgrade" means they are sending me a new test tube to spit in, and mail it back to them. They will then redo my entire DNA using the V5 chip, which includes all 8 (currently known) mutations of the hyperacusis gene.

 

[Lucifer]

@Lucifer, I don't know what CGRP med(s) the mice are receiving, but I did hear of a human hyperacusis patient who has tried two different CGRP meds for hyperacusis, Emgality and Nurtec, though I don't know anything about their experience with them. I wonder if anyone else has tried CGRP meds. I don't recall anyone posting here about trying CGRP meds for hyperacusis, I wonder if they could be helpful.

Would it be possible to ask them about their experience with CGRP meds such as Emgality and Nurtec?

I had a look at what those CGRP meds are and they are supposed to treat migraines and they administer it through an injection. I thought it was a new drug that they are testing but that doesn't appear to be the case.

Other than finding out the Cx26 gene causes hyperacusis and susceptibility to noise, there are no drugs currently in testing that are supposed to reduce hyperacusis.

The only drug that seems to have potential with hyperacusis & tinnitus was OTO-413 due to outer hair cell and synapses regrowth but the likelihood of them restarting OTO-413 Phase 2b trial is slim.

 

[Brian Newman]

→ Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise

I've read this article but I'm having trouble with understanding the terminology in this. I thought someone else could explain it to me.

They talk about GJB2 (Cx26) mutations. I'm not sure if this article is saying reducing GJB2 (Cx26) will reduce hyperacusis & susceptibility to noise, or the other way around, or something else I'm not understanding.

Maybe someone like @Nick47, @Diesel or @Chad Lawton could have a read through it.

Nice find. Really interesting. Makes sense to be a gene issue because of all the people abusing their ears and nothing happens.

 

[lymebite]

Would it be possible to ask them about their experience with CGRP meds such as Emgality and Nurtec?

I asked them today. They said those CGRP meds did not help with the hyperacusis, unfortunately.

Of course that is just one data point. But would have been nice if it had been a positive result for that one person. I asked another person today who has been contemplating trying CGRP meds for hyperacusis, but they said they have not yet gone forward due to concerns about possible side effects.

So right now, to my knowledge, we have a sample size of one person with hyperacusis who has tried CGRP meds.

 

[Markku]

The only way to know if you have the gene mutation is to get your DNA sequenced from 23andMe or a similar company. You spit in a test tube, mail it back, and a few weeks later you get all of your DNA reports online, including whether or not you have one or more of the GJB2 mutations.

I've done the V5 23andMe. There are indeed 8 tested markers for the GJB2: c.35delG, W24X, M34T, V37I, c.167delT, c.235delC, S139N, R143W.

Apparently I don't have this:

 

[Lucifer]

Nice find. Really interesting. Makes sense to be a gene issue because of all the people abusing their ears and nothing happens.

It's unfortunate that we probably have the Cx26 gene which has caused us to get hyperacusis and tinnitus more easily compared to others who have suffered with noise damage for years with no hyperacusis or tinnitus.

I thought that article might have talked about drugs that might help us but it only talks about the Cx26 gene.

So if the Cx26 gene is causing us to have hyperacusis or tinnitus more easily, there are no current drugs to help us.

 

[lymebite]

I've done the V5 23andMe.

My V5 test kit from 23andMe arrived today. Tomorrow I will mail it back to them.

Though to the point made by @Lucifer about no current drugs being available for hyperacusis or tinnitus, there is nothing actionable for me to do if I have one of the 8 mutations. So it is for information only at the present time.

 

[Lucifer]

@lymebite, what I was trying to ask is that, since we know that Cx26 gene is causing hyperacusis and susceptibility to noise, what would the researchers' next step be now?

Even if they were to somehow get rid of the Cx26 gene, I don't think it will help people who already have hyperacusis or tinnitus and we would need a different solution to solve this problem.

 

[lymebite]

what would the researchers' next step be now?

I think that is an excellent question, and I have the same question, but I don't know. Science is not my skill set. My hope is that this Cx26 gene research finding is something that the authors, or other researchers, will be be able to build on.

 

[Lucifer]

I think that is an excellent question, and I have the same question, but I don't know. Science is not my skill set. My hope is that this Cx26 gene research finding is something that the authors, or other researchers, will be be able to build on.

From past research it was stated that hyperacusis could be caused by outer hair cell or synapse loss (which is important for speech-in-noise and audiogram tests) which is triggering Type 2 nerve fibres which is causing hyperacusis.

From the results of OTO-413 Phase 2a trial with the 0.3 mg, there were improvements in speech-in-noise tests which may be due to either outer hair cell or synapse regrowth. I look at the data but I don't think they did any audiogram testing or maybe it was somewhere in the slides where I might have missed it so if someone knows, please correct me.

OTO-413 was our best bet in regrowing outer hair cells and synapses and I hope that this is not the end for them and they continue with OTO-413 at the 0.3 mg dose. The efficacy of OTO-413 was much better compared to FX-322.

Speech-in-noise and audiograms are more important than speech in a quiet setting and that's why I thought OTO-413 is likely to be more successful than FX-322 as more people have trouble listening to words in noise and with audiograms.

 

[Nick47]

Isn't this information that should be collected in the UK Biobank?

 

[IndyMLVC]

The V4 chip was upgraded to the V5 chip in June 2020.

That isn't accurate. I had mine done in 2019 and it was V5.

 

[lymebite]

That isn't accurate. I had mine done in 2019 and it was V5.

I don't know what the correct info is. I pulled the June 2020 date from this page on the 23andMe website, which isn't crystal clear, it's more about the upgrade process. But regardless, anyone can log into their account and find out what chipset they are on, don't need to guess at the dates. Mine from 2015 was definitely V4, so if yours from 2019 was V5, then I suppose the changeover date was sometime after 2015 and before 2019.

Upgrading To 23andMe's Newest Chip Version

All Chip Upgrade kits ordered after June 23, 2020 are assigned to the original profile, but need to be registered in order for the lab to process the sample. To register your Chip Upgrade kit, visit 23andme.com/start and sign into your account.

If your Chip Upgrade kit was purchased before June 23, 2020, you do not need to register your kit, as the Chip Upgrade barcode will be automatically registered to your original profile.

Source: https://customercare.23andme.com/hc...68-Upgrading-to-23andMe-s-Newest-Chip-Version

 

[Nick47]

@lymebite, what I was trying to ask is that, since we know that Cx26 gene is causing hyperacusis and susceptibility to noise, what would the researchers' next step be now?

Even if they were to somehow get rid of the Cx26 gene, I don't think it will help people who already have hyperacusis or tinnitus and we would need a different solution to solve this problem.

The CGRP antagonist they used in the mice is not available, although they said similar ones on the market are.

Rimegepant? 1.25mg/kg.

Remember they were mice and I think they injected it into the cochlear rather than systemic.

 

[StoneInFocus]

Even if they were to somehow get rid of the Cx26 gene, I don't think it will help people who already have hyperacusis or tinnitus and we would need a different solution to solve this problem.

Why do you think so?