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It’s not, and if you don’t understand this, you’ve never been around the deaf community before. My college language agreement was filled through sign language. Learning about the deaf community was fascinating.

This is good news, but I still have concerns.

Otoferlin [1] uses calcium as a cofactor. These mutations happen for a reason. The enzyme is not only located in the ear, but also in the brain and bone marrow [2].

Will there be repercussions if the virus leaves the local area when the therapy is injected?

These OTOF mutation have their highest expression in the Turkish population. Many people with other variations of this gene only experience deafness when they have a fever[3]. So in my opinion, I would like to see ten year outcomes before celebrating.

[1] https://www.uniprot.org/uniprotkb/Q9HC10/entry

[2] https://www.proteinatlas.org/ENSG00000115155-OTOF/tissue

[3] https://www.frontiersin.org/journals/cell-and-developmental-...


The Regeneron press release mentions that the therapy includes a hair cell specific regulator for the gene:

https://investor.regeneron.com/news-releases/news-release-de...

That of course doesn't rule out problems, but the treatment doesn't naively turn on the protein production either.


There are a lot of risks with retroviral genetic therapy. However, there are a lot of upsides. I think what we need most, is to gain as much knowledge as possible, to ensure we can treat anything untoward as a result.

In terms of 'leaving the local area', there was a recent treatment intended to be done on one eye first, just in case it did not go as planned. It spread to the other eye:

https://www.cam.ac.uk/research/news/gene-therapy-injection-i...

Viral vector DNA was detected in the anterior segment, retina and optic nerve of the untreated eye. The unexpected visual improvement observed in the untreated eyes could therefore reflect the interocular diffusion of rAAV2/2-ND4. Further investigations are needed to confirm these findings and whether other mechanisms are contributing to this bilateral improvement.

Seeing as the eye was directly injected, it's unclear how it spread. Blood, likely.


Yes, some of the vector was likely cleared from the AH and exposed the contra lateral eye

Patients with fever induced hearing loss regardless of OTOF mutations were specifically excluded (see inclusion criteria on clinical trials.gov for NCT05788536).

With regard to your point about shedding or systemic exposure. If non functional copies of OTOF in the other tissues expressing the gene were to be replaced by functional copies, what is the concern? How would that negatively impact patients? Doesn’t seem like this would/should be a concern.

Also, mutations don’t have to be teleologically beneficial to occur and persist. They can persist because they are not fatal nor do they impair reproductive competence.


Good to have concerns, but if I was deaf I'd weigh them based on how much I want to hear and discuss the risks with my doctor.

Personally I think I would want to hear once in my life, even if it meant a potentially shorter life.

I'm glad the Trump admin prioritized this.


This was not a political decision. These kind of accelerated paths have been available for years for a wide variety of therapies.

> and to Cook that was grow the company.

If you do not see this as teh problem with Tim Cook then I have a gold bar to give you.

https://www.macrumors.com/2025/08/07/tim-cook-gift-to-trump/

I want ethical companies that grow because of good products, not because of market capture and bribes.


And Steve Job's Apple was an ethical company because... he pushed people to produce sleek devices? Which is fine, but then I'd propose that growing the company was ethical because it helped retirement portfolios and employed lots of people. The only Apple product I own is a prime-day deal Beats Pill, but I'm not going to claim that Apple grew because of bribes. People do seem to love their products, in ways I find irrational sometimes.

> And Steve Job's Apple was an ethical company because...

Did I say that?


Yep, Cooks new role is essentially lobbyist.

I'm not going to argue your wants with you because they are your own. Don't buy Apple products if you don't like the way they operate as a company. I don't particularly care for appeasing the administration, either, but it's not like Cook broke the system, so I'm not going to dance on his retirement over it.

Where can I get my gold bar, please?


I like Apple's products. I just purchased an iPhone 17 Pro. It does not mean I cannot still criticize them because of their monopolistic practices.

I was doing Apple support since 1995, I saw how they changed.

I mean, they certainly would never have given Trump a gold bar to forgive this case now, would they?

https://www.cnn.com/2024/03/21/tech/apple-sued-antitrust-doj...


> I want ethical companies

This will never exist.

We should want regulated and lawful companies, which we don't have right now.


> I want ethical companies that grow because of good products, not because of market capture and bribes.

Then avoid becoming a customer/user of companies that grew because of market capture or bribes.


Yes, the reason Apple was so successful at Cook's helm is because he gifted Trump a plaque.

Why do you think they got most of their components exempted from tarrifs?

I'm aware of the open bribery by the administration. That has nothing to do with my comment.

Right, and without that open bribery they would have had 100% tarrifs on all of their iphones, macbooks and semiconductors, which is an overwhelming portion of their revenue.

Now obviously, this only covers a small portion of Tim's reign over apple, but is it not fair to say you'd have a different overall view of his tenure if he was an honest businessman and ate the tarrifs like he was supposed to, probably tanking the stock in the process?


I would probably have a stronger gripe with the ridiculousness of the tariffs than Tim Cook's refusal to bribe the president. Also, to say that not bribing would make him an "honest businessman" is slightly unfair. He has a fiduciary duty to the shareholders, and if he is aware that lobbying to the president personally to avoid tariffs is what it takes to avoid tanking Apple's profit and share price, he is required to do that.

When you realize that everything "we" see is common hallucination, then it will all make sense. The human mind creates the image of a tree, the eye just takes in the light. Change the eye or the mind and our hallucination changes.

So these mushrooms change the mind in a very specific way, but no more strange than putting on red tinted glasses.

Speaking as someone who has involuntary hallucinations, this is a reality taken for granted by most people. I have very different hallucinations when I am dep[ressed vs when I am manic. And you are on the right track in my opinion that "the drug induces the same reaction in a human body, no matter its location."


Grand Unified Theory:

Low intracellular ATP/GTP.

https://www.science.org/doi/10.1126/sciadv.adq6077


Nah, lithium is only treating something that is occurring much deeper: low glucose transport in the brain.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8772148/

This is why APoE e4 alleles are a risk factor, because they control glucose transport.

https://www.nature.com/articles/s41398-025-03550-w

The brain is just losing energy.


I would people need to read the #1 post on HN today to get a clue why they are failing with Alzheimer's.

https://www.scientificamerican.com/article/amateur-armed-wit...

Just like that math problem, we are starting off with wrong thinking right from the beginning. Some researchers are already talking about this but the plaques are actually a protective response to a metabolic problem in the brain which has to do with glucose transport.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8772148/

This is why people with dementia and Alzheimer's crave sweets so much:

https://helpdementia.com/why-dementia-patients-crave-sweets-...

Alzheimer's is not a neurological problem, it is a metabolic problem.


You may have naturally low dopamine production or release (or low ATP or GTP). Everyone will react differently because genetics so you are right, everyone needs to be mindful of their reaction.

You might want to look at this pathway, and the enzymes, and the cofactors for these enzymes:

https://www.researchgate.net/profile/Pingyuan-Gong/publicati...

Tyrosine 3-monooxygenase (TH) needs Iron

Aromatic-L-amino-acid decarboxylase (DDC) needs B6


Yes, same here. I have schizoaffective disorder and realizing that caffeine affected my mental health so drastically was the beginning of my recovery journey 30 years ago. I can use caffeine now as a drug when I need it. Same with alcohol.

Just because your heart rate is lower does it mean you’re any healthier however. This is just ridiculous measurement it means nothing.

The sauna might be acting like any other drug. There are a lot of drugs that will lower nighttime heart rate. Does that mean those drugs are healthier for you?


If your resting heart rate is lower without any drugs, it indicates that your heart can cause sufficient oxygen to be delivered to your organs with less effort than if it were higher. That can be caused by a variety of things (including stroke volume, capillary dilation and general obstruction (or not) of blood vessels). These are all good proxies for general health.

Drugs lowering your resting heart rate do not indicate this in the same way.


You think being n a Sauna is not a drug (effectively)?

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