I’ve been following this for a personal interest. Decibel Therapeutics was working on this for quite a while with a lot of success before they were acquired by Regeneron and it was very promising but the next ones in the pipeline were personally relevant. They’re a fix for the GJB2 gene mutation that causes hearing loss. Unlike the OTOF error, this one is progressive so you have to get to it fast.
My wife and I carry mutations to the gene so we’ve done preimplantation genetic testing to select the embryos that haven’t been affected and our daughter can hear just fine! We have enough unaffected embryos that we can have another child but if we can have a third we’d probably want a boy[0] and both of our male embryos are coincidentally affected. If somehow we’ve managed to delay long enough for the corresponding Decibel TX AAV.103 gene therapy to come to market, then this will be an incredible triumph of modern science and technology over nature.
> If somehow we’ve managed to delay long enough for the corresponding Regeneron AAV.103 gene therapy to come to market, then this will be an incredible triumph of modern science and technology over nature.
How does this relate to offspring exactly? The "delay long enough" part makes no real sense to me. Also, no treatment is usually always 100% effective, so I don't understand the "delay long enough" part either. Plus, there is no "nature" anymore than there is a divine being. What this here is simply the difference between having technology; and not having it. "Nature" is not part of any equation here other than regular genetic information and how it is changed, "naturally".
That’s about when I found out about the Decibel Tx therapy ongoing. If I have any underlying motivation it’s that maybe we could get earlier access to the therapy. Sadly, scientific studies don’t admit fan clubs preferentially.
The delay long enough is that we have all of our embryos in cold storage and we’ve been able to select the ones that are unaffected. My daughter is a bit over a year old and we’re planning a second implantation in the next few months where we will obviously select an unaffected embryo. But a third child, if my wife wishes, will be another 3 years from now. If PGT allowed us to go from a 2023 plan to have kids to a 2029 son born from a male embryo we were able to keep in cold storage till a therapy was available to give him hearing at birth, I think that qualifies as being able to delay long enough.
And about the Nature comment, imagine it a form of metonymy. I’m just referring to random chance and genetic mutation and so on. I’d call my glasses a triumph of man over nature too :)
Although this affects a small number of people / kids per year - this is a great development. There's a related article^ which had a very moving account from a mom whose son has received this treatment.
This is really cool and awesome for people with this condition!
Unfortunately, I have seen treatments arrive for almost every type of deafness except the one affecting me. I contracted the mumps at a very young age, approximately 5 months old, and I now have nerve deafness in one ear making me completely deaf in that ear. The ear drum still operates, as I feel pain in that ear when around extremely loud noises. I absolutely do not want a cochlear implant, so it seems I may be stuck like this for the rest of my life. :-(
Coincidentally, I'm reading this at the doctor's office reception, waiting to check my (potentially genetic) hearing loss. Hope it's something simpler, but good to know there are advances in this area.
This is a very cool example of a targeted gene therapy for a very specific type of hearing loss. As the article says it only applies to a subtype of genetic hearing loss which makes up 2-8% of genetic cases, but it’s nice to see such niche therapies being developed and approved despite the smaller number of people who could benefit. It underwent an accelerated review through a new program met to fast track treatments for rare conditions like this which would normally be difficult to get approved due to the small scale.
Very positive news. I have something similar but in a much more difficult gene with different manifestation, but at least this gives me hope that something might come up in 1-2 decades.
Fingers crossed. I thought the same when I had heard Stefan Heller at Stanford give a talk 15+ years back. I am sure progress is happening but Biology is hard and the hope is AI and other developments are giving it a push
"These kind of genetic therapies seem to reinforce this idea of deafness being a problem in need of eradication, and that the only solution for disabled people to fully assimilate into society is through a medical intervention," says Jaipreet Virdi
Consider this from the perspective of a deaf person. While it seems silly from the perspective of a hearing person, a lot of people in the deaf community are concerned that they are viewed as having a problem needing to be fixed, rather than competent, highly functioning people.
To some in the Deaf community, being Deaf is like skin color or hair color or height or left handedness; a normal variation of humanity with its own culture. "Fixing" reads as genocide to them, and it's not entirely unwarranted.
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.
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.
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:
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.
You're right, but because nuance isn't allowed on HN, you'll be down voted.
Primarily the focus has shifted to faster approvals with evidence for new methods and drugs coming down to one high quality trial, and removed stipulations for randomized control trials for ultra rare diseases.
“President Trump promised to accelerate cures for American families — and we are delivering, especially for children with ultra-rare diseases who cannot afford to wait,” said Health and Human Services Secretary Robert F. Kennedy, Jr. “We are cutting unnecessary red tape, aligning regulation with modern biology, and clearing a path for breakthrough treatments to reach the patients who need them most.”
“This guidance is a critical step the FDA is taking to tailor our regulatory approach to patients with ultra-rare conditions,” said FDA Commissioner Marty Makary, MD, MPH. “It is our priority to remove barriers and exercise regulatory flexibility to encourage scientific advances and deliver more cures and meaningful treatments for patients suffering from rare diseases.”
Now, you can be caught in the fun partisan civil war on emotions or simply look at outcomes. Good work being done at the FDA, just fact.
You're presumably referring to the ideologically driven cuts at the NIH and a complete misunderstanding of the efficacy-effectiveness gap in macro-level Research outcomes at the FDA? The ones that have led many prominent Professors of Medicine like Celine Gounder to conclude that “The current administration is waging a war on science.”?
RFKs deleterious impact on scientific research and its funding is well documented in the context of the NIH. 2025's Bethesda Declaration ably details the culture of 'fear and suppression' present under RFK, and the $9.5bn in grants and $2.5bn in contracts he had cut, impacting over 2,000 projects. It concludes with a chilling warning regarding plans to cut up to 40% of NIH's $48 billion budget in the future.
At an FDA level, the same strategy was clearly evident last August when Trump fired CDC Director Monarez after clashing heads with RFK over vaccine policies barely a month into her role. Kennedy had demanded she fire career agency officials and commit to backing his own advisers. Four high-ranking officials resigned in support with Monarez.
In a similar vein, RFK then performed a clean sweep of the legacy 17 person vaccine panel in favour of his handpicked eight person vaccine panel – half of whom share ideologue Kennedy’s famous distrust of vaccines. Democrats on the Senate Health Committee summarised it blunty in an open-letter to RFK: “By removing all 17 of ACIP’s members and replacing them with eight individuals handpicked to advance your anti-vaccine agenda, you have put decades of non-partisan, science-backed work – and, as a result, Americans’ lives – at risk."
Moderna CEO Stephane Bancel subsequently said the company would not invest in new phase 3 infectious disease vaccine trials due to growing opposition from U.S. officials to immunizations.
This was then further compounded when the FDA RTF'd Moderna's new Flu Vaccine on spurious grounds in February, with the Alliance for mRNA Medicines calling the decision “unprecedented,” claiming the FDA was in “disarray,” and warned of a “threat to public health.”
Even last month a federal judge concluded RFKs actions re: the panel were not lawful, and that earlier votes by the panel to downgrade recommendations for hepatitis B vaccines for newborns and COVID-19 shots were invalid, blocking the Trump administration’s much publicised overhaul of the childhood vaccine schedule.
The only partisan stance at the moment would be not acknowledging the systemic dismantling of these scientific safeguards and institutions to the detriment of the American population as a whole.
My wife and I carry mutations to the gene so we’ve done preimplantation genetic testing to select the embryos that haven’t been affected and our daughter can hear just fine! We have enough unaffected embryos that we can have another child but if we can have a third we’d probably want a boy[0] and both of our male embryos are coincidentally affected. If somehow we’ve managed to delay long enough for the corresponding Decibel TX AAV.103 gene therapy to come to market, then this will be an incredible triumph of modern science and technology over nature.
Here’s hoping!
If you’re curious about this process, I’ve written about it here: https://wiki.roshangeorge.dev/w/IVF
And here’s the treatment pipeline image I nicked off decibel TX’s website before they were acquired a year and a half ago https://wiki.roshangeorge.dev/w/File:Screenshot_Decibel_Tx_P...
I’m super thrilled everything has gone through so fast.
0: it would just be nice to have children of both genders; a weak preference - if I have 3 daughters I would be thrilled anyway
But, ignoring this, you wrote:
> If somehow we’ve managed to delay long enough for the corresponding Regeneron AAV.103 gene therapy to come to market, then this will be an incredible triumph of modern science and technology over nature.
How does this relate to offspring exactly? The "delay long enough" part makes no real sense to me. Also, no treatment is usually always 100% effective, so I don't understand the "delay long enough" part either. Plus, there is no "nature" anymore than there is a divine being. What this here is simply the difference between having technology; and not having it. "Nature" is not part of any equation here other than regular genetic information and how it is changed, "naturally".
That’s about when I found out about the Decibel Tx therapy ongoing. If I have any underlying motivation it’s that maybe we could get earlier access to the therapy. Sadly, scientific studies don’t admit fan clubs preferentially.
The delay long enough is that we have all of our embryos in cold storage and we’ve been able to select the ones that are unaffected. My daughter is a bit over a year old and we’re planning a second implantation in the next few months where we will obviously select an unaffected embryo. But a third child, if my wife wishes, will be another 3 years from now. If PGT allowed us to go from a 2023 plan to have kids to a 2029 son born from a male embryo we were able to keep in cold storage till a therapy was available to give him hearing at birth, I think that qualifies as being able to delay long enough.
And about the Nature comment, imagine it a form of metonymy. I’m just referring to random chance and genetic mutation and so on. I’d call my glasses a triumph of man over nature too :)
^: https://www.npr.org/2026/04/23/nx-s1-5795526/deafness-gene-t...
Unfortunately, I have seen treatments arrive for almost every type of deafness except the one affecting me. I contracted the mumps at a very young age, approximately 5 months old, and I now have nerve deafness in one ear making me completely deaf in that ear. The ear drum still operates, as I feel pain in that ear when around extremely loud noises. I absolutely do not want a cochlear implant, so it seems I may be stuck like this for the rest of my life. :-(
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-...
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.
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.
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.
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.
Primarily the focus has shifted to faster approvals with evidence for new methods and drugs coming down to one high quality trial, and removed stipulations for randomized control trials for ultra rare diseases.
Nuance is fine. There's not much nuance in the parent post.
Latest in this area: https://www.fda.gov/news-events/press-announcements/fda-laun...
“President Trump promised to accelerate cures for American families — and we are delivering, especially for children with ultra-rare diseases who cannot afford to wait,” said Health and Human Services Secretary Robert F. Kennedy, Jr. “We are cutting unnecessary red tape, aligning regulation with modern biology, and clearing a path for breakthrough treatments to reach the patients who need them most.”
“This guidance is a critical step the FDA is taking to tailor our regulatory approach to patients with ultra-rare conditions,” said FDA Commissioner Marty Makary, MD, MPH. “It is our priority to remove barriers and exercise regulatory flexibility to encourage scientific advances and deliver more cures and meaningful treatments for patients suffering from rare diseases.”
Now, you can be caught in the fun partisan civil war on emotions or simply look at outcomes. Good work being done at the FDA, just fact.
RFKs deleterious impact on scientific research and its funding is well documented in the context of the NIH. 2025's Bethesda Declaration ably details the culture of 'fear and suppression' present under RFK, and the $9.5bn in grants and $2.5bn in contracts he had cut, impacting over 2,000 projects. It concludes with a chilling warning regarding plans to cut up to 40% of NIH's $48 billion budget in the future.
https://en.wikipedia.org/wiki/Bethesda_Declaration
At an FDA level, the same strategy was clearly evident last August when Trump fired CDC Director Monarez after clashing heads with RFK over vaccine policies barely a month into her role. Kennedy had demanded she fire career agency officials and commit to backing his own advisers. Four high-ranking officials resigned in support with Monarez.
In a similar vein, RFK then performed a clean sweep of the legacy 17 person vaccine panel in favour of his handpicked eight person vaccine panel – half of whom share ideologue Kennedy’s famous distrust of vaccines. Democrats on the Senate Health Committee summarised it blunty in an open-letter to RFK: “By removing all 17 of ACIP’s members and replacing them with eight individuals handpicked to advance your anti-vaccine agenda, you have put decades of non-partisan, science-backed work – and, as a result, Americans’ lives – at risk."
Moderna CEO Stephane Bancel subsequently said the company would not invest in new phase 3 infectious disease vaccine trials due to growing opposition from U.S. officials to immunizations.
This was then further compounded when the FDA RTF'd Moderna's new Flu Vaccine on spurious grounds in February, with the Alliance for mRNA Medicines calling the decision “unprecedented,” claiming the FDA was in “disarray,” and warned of a “threat to public health.”
Even last month a federal judge concluded RFKs actions re: the panel were not lawful, and that earlier votes by the panel to downgrade recommendations for hepatitis B vaccines for newborns and COVID-19 shots were invalid, blocking the Trump administration’s much publicised overhaul of the childhood vaccine schedule.
The only partisan stance at the moment would be not acknowledging the systemic dismantling of these scientific safeguards and institutions to the detriment of the American population as a whole.