9 ms·

First gene therapy for Tay-Sachs disease successfully given to two children

205 points by daegloe 5y ago

beams_of_light 5y ago
>We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. Wish this were not the case.
- bckr 5y ago
  I think it's okay to express this, but would be more valuable if you added more to the conversation e.g. what you positively desire.
  - inglor_cz 5y ago
    Rare diseases need some public funding. Not only for ethical reasons, but we may also find out very nontrivial things about our own biology this way.
    - loeg 5y ago
      They have some public funding.
    - contravariant 5y ago
      We probably shouldn't put the main focus on rare disease but on genetic manipulation in general. It would be much more valuable to be able to cure arbitrary genetic defects than just the ones that are somewhere between uncommon and extant.
    - DoreenMichele 5y ago
      Not only for ethical reasons, but we may also find out very nontrivial things about our own biology this way. If it's looked at through the right lens, yes. I'm not sure if genetic research is actually the optimal means to find such takeaways though.
      - dekhn 5y ago
        I mean, this has definitely happened in the past; study of various rare genetic diseases has elucidated and illuminated the processes by which diseases occur at a molecular level, and often have utility far outside the original rare disease. As to whether that means it's an effective payoff if you put more money in rare diseases (and therefore less into non-rare diseases), I can't say, so instead, I have a portfolio with a small but not tiny amount for the collection of all rare diseases.
- mym1990 5y ago
  It's weird to say 'only' since I assume that a lot more went into this effort other than funding. There are a lot of initiatives that have a lot of funding, but little success. Either way, this result is certainly better than nothing, or waiting years/decades for public funding.
  - Talanes 5y ago
    'Only' implies that the funding was necessary, not that the funding was fully responsible. Also consider that 'only' was said by the researchers. From their pov the effort is a given, because that is what they control, while the funding is an anomalous outside factor.
- hammock 5y ago
  - Shared404 5y ago
    From https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html : > Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith.
    - deleted 5y ago
      [deleted]
    - hammock 5y ago
      Fair enough. Let's hope some charity decides to take up the cause for those children whose families cannot support the cost of treatment.
- BurningFrog 5y ago
  I expect most of the cost is regulatory. Lighter regulation around rare "small market" diseases might save a lot of lives. And money.
  - soldehierro 5y ago
    > Lighter regulation around rare "small market" diseases might save a lot of lives. And money. Orphan drugs for rare diseases are already subject to less regulation.
- halukakin 5y ago
  Wish governments would spare funding to these research efforts.
  - thehappypm 5y ago
    It’s just tough because resources are not unlimited. You’ll save many more lives focusing on new antibiotics and then you will on Tay-Sachs. I don’t think there’s enough researchers in the world to focus on every single rare disease.
LegitShady 5y ago
Hopefully this is long term successful and the first step in curing a lot of conditions like this.
- mym1990 5y ago
  If you're interested in learning more, the book Code Breaker is a great background to some of the steps that were taken to get us to where we are today! This work has been decades in the making :)
bckr 5y ago
This is incredibly moving. It can feel like there's no good news in the world, and that techno-optimism isn't founded. But these 2 kids are a lot healthier than than they would have been without this incredible invention. This is the kind of stuff we can hold on to. Thanks for sharing.
- ch4s3 5y ago
  They would die otherwise, painfully I might add. Gene therapy is posed to be a revolution that makes antibiotics look like band aids.
  - dekhn 5y ago
    It was posed to be a revolution when I started my career, some 30 or so years ago. The pace is glacial. There is no systematic way to deal with this; nearly every disease has its own details, and individuals differ so many treatments have to be personalized. Many of the changes we make, we don't really know how or why they work. I've left human biology and returned to model organisms because the experiments allow for much less ambiguity.
    - ch4s3 5y ago
      Yeah it seems like that was the norm in the past, but it’s looking like CRISPR and it’s successors are shaped to change that. As long as the set of relevant genes is small, and in a small enough number of cells it should be possible to scale up. Genetic degenerative diseases of the eye, sickle cell, and similar show a lot of promise.
- chaostheory 5y ago
  It’s good news, but it doesn’t mean that there still aren’t more challenges to overcome. I think the article ends on a really important note: “The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low. We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant”
CoastalCoder 5y ago
I was a little surprised that the researcher talked only about stopping disease progression, rather than reversal. Especially for the 7-month old. I assumed that at that age, the brain was still growing / adapting in ways that could work around the earlier problems. But now that I think about it, I've heard that oxygen deprivation during birth can cause permanent impairment.
- halukakin 5y ago
  Reading the article, I'm not seeing much info on how the results were 7 months old in terms of brain development. At that age, one would expect brain development to improve. I hope the researchers discuss this in more detail in future news.
- DoreenMichele 5y ago
  For genetic conditions like this one, it's typically a positive feedback loop -- aka vicious cycle -- where the sicker they get, the sicker they get and it accelerates. Stopping the normal progression would be a huge win in its own right.
drran 5y ago
IMAYousaf 5y ago
I don't have anything to add except that for some reason, I viscerally remember the first time I heard of Tay-Sachs disease in a high school classroom through a video about genetics. Something made me feel so disturbed about this one disease above all else because of the seeming hopelessness of the situation coupled with the rampant cruelty of how it kills kids from the inside and seemingly reverses developmental progress. I don't know why I just remember the moment I learned about this, but this is great news. Hopefully this is the first in many such therapies.
photon_lines 5y ago
"The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low. We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. This grassroots approach is a common theme in ultrarare disease research – development and testing are often supported by parents, foundations and federal grants." FYI - if anyone here is interested in helping these kinds of causes, a company called Orchard Therapeutics provides similar treatments and has just signed a historic agreement for reimbursement for treating MLD patients in Europe (you can read more about it here: https://www.globenewswire.com/news-release/2022/02/04/2378990/0/en/Orchard-Therapeutics-Announces-Historic-Agreement-Making-Libmeldy-Available-by-NHS-England-for-MLD-Patients.html https://www.globenewswire.com/news-release/2022/02/04/237899...). Also big discretion: I do have a lot invested in the company and I have incurred significant losses since deciding to invest in it. In the brilliant world of pyramid schemes vested around crypto-coins and NFTs, I don't regret anything and will keep buying more shares to support the dignity of human life.
godmode2019 5y ago
Can someone explain who this works? """ I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier. Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions. In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. """ They use a monkey virus to deliver two mRNA codes to brain cells, the mRNA after being transcribed, tells the brain cells to create HexA to deal with the target enzyme. Okay, I get that much. But how on earth does this work. """ these DNA instructions enter the nucleus of these cells and stay there """ I thought mRNA could not alter DNA and it was by definition broken down after use by the cell, ie short term by definition?
- The_rationalist 5y ago
  [dead]
- dahfizz 5y ago
  Plenty of viruses use DNA and not RNA. The virus injects it's DNA sequence into the host DNA. This is why people have "flare ups" of herpes/cold sores. That is a DNA virus, so once the cells are infected they carry that DNA sequence forever, even after the cells divide.
- JunkDNA 5y ago
  They’re not using mRNA. They are using a viral vector that contains DNA.
The_rationalist 5y ago
[dead]
scott113341 5y ago
I was actually thinking about Tay-Sachs this morning on a walk, after I passed by a church with a billboard out front that says "Christ died for all, even babies in the womb". I learned about Tay-Sachs in high school biology. I think we watched a short documentary on it, as an example of genetic inheritance, and the importance of enzyme function. I remember being so surprised that something so simple (absence of one protein) could be so horrible. A beyond-grim prognosis, and immeasurable/unavoidable suffering for everyone involved. Since then, it's been something that I can't reconcile with the existence of a higher benevolent being. I'm no expert, but it made a lasting impression on me. I'm so uplifted that researchers have made progress on curing this senseless disease.
- pyuser583 5y ago
  I mean I come from a religious family with a history of genetic illness. I have quite a few relatives who died in infancy. Their lives mattered greatly, and they improved their families lives immensely. I get that it’s hard to see a child who is going to die as valuable, and I don’t judge people who disagree. But the value is very much there, and initial shock of terror and disgust isn’t necessarily a good ethical guide.
  - charlieflowers 5y ago
    I don’t think GP is questioning whether those dying infants’ lives were valuable. I think their point is, those lives were valuable, so how could a benevolent, all-powerful creature allow them to suffer and die merely due to a genetic bug.
starchild_3001 5y ago
This is actually the 2nd brain gene therapy research I've seen. In the Phase I trial below, injecting telomerase and klotho AV vectors into CNS/brain was safe and it improved cognitive scores of 5 dementia patients after 1 yr follow up. Interview: https://www.youtube.com/watch?v=i__oZyxgLC0 https://www.youtube.com/watch?v=i__oZyxgLC0 Paper: https://www.linkedin.com/posts/patrick-e-sewell-md-a994774_gene-therapy-for-dementia-activity-6863849206608732160-h9WW/ https://www.linkedin.com/posts/patrick-e-sewell-md-a994774_g... This space will hopefully get very big. Mice lifespans were extended 25-40% (massive!) through similar techniques. See Dr George Church Gene Therapy for more.
UltraViolence 5y ago
Gene therapy is the game-changer which will enable us to eventually cure cancer. I've been proposing that government stop all investment in refining non-gene therapies, such as radiation and chemotherapy, and to plow everything we have into gene-therapy. Cancer is essentially a genetic disease and we can solve it by repairing the faulty genes, just as with Tay Disease.

205 points by daegloe 5y ago

>We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. Wish this were not the case.

bckr 5y ago
I think it's okay to express this, but would be more valuable if you added more to the conversation e.g. what you positively desire.
- inglor_cz 5y ago
  Rare diseases need some public funding. Not only for ethical reasons, but we may also find out very nontrivial things about our own biology this way.
  - loeg 5y ago
    They have some public funding.
  - contravariant 5y ago
    We probably shouldn't put the main focus on rare disease but on genetic manipulation in general. It would be much more valuable to be able to cure arbitrary genetic defects than just the ones that are somewhere between uncommon and extant.
  - DoreenMichele 5y ago
    Not only for ethical reasons, but we may also find out very nontrivial things about our own biology this way. If it's looked at through the right lens, yes. I'm not sure if genetic research is actually the optimal means to find such takeaways though.
    - dekhn 5y ago
      I mean, this has definitely happened in the past; study of various rare genetic diseases has elucidated and illuminated the processes by which diseases occur at a molecular level, and often have utility far outside the original rare disease. As to whether that means it's an effective payoff if you put more money in rare diseases (and therefore less into non-rare diseases), I can't say, so instead, I have a portfolio with a small but not tiny amount for the collection of all rare diseases.
mym1990 5y ago
It's weird to say 'only' since I assume that a lot more went into this effort other than funding. There are a lot of initiatives that have a lot of funding, but little success. Either way, this result is certainly better than nothing, or waiting years/decades for public funding.
- Talanes 5y ago
  'Only' implies that the funding was necessary, not that the funding was fully responsible. Also consider that 'only' was said by the researchers. From their pov the effort is a given, because that is what they control, while the funding is an anomalous outside factor.
hammock 5y ago
- Shared404 5y ago
  From https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html : > Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith.
  - deleted 5y ago
    [deleted]
  - hammock 5y ago
    Fair enough. Let's hope some charity decides to take up the cause for those children whose families cannot support the cost of treatment.
BurningFrog 5y ago
I expect most of the cost is regulatory. Lighter regulation around rare "small market" diseases might save a lot of lives. And money.
- soldehierro 5y ago
  > Lighter regulation around rare "small market" diseases might save a lot of lives. And money. Orphan drugs for rare diseases are already subject to less regulation.
halukakin 5y ago
Wish governments would spare funding to these research efforts.
- thehappypm 5y ago
  It’s just tough because resources are not unlimited. You’ll save many more lives focusing on new antibiotics and then you will on Tay-Sachs. I don’t think there’s enough researchers in the world to focus on every single rare disease.

LegitShady 5y ago

Hopefully this is long term successful and the first step in curing a lot of conditions like this.

mym1990 5y ago
If you're interested in learning more, the book Code Breaker is a great background to some of the steps that were taken to get us to where we are today! This work has been decades in the making :)

bckr 5y ago

This is incredibly moving. It can feel like there's no good news in the world, and that techno-optimism isn't founded. But these 2 kids are a lot healthier than than they would have been without this incredible invention. This is the kind of stuff we can hold on to. Thanks for sharing.

ch4s3 5y ago
They would die otherwise, painfully I might add. Gene therapy is posed to be a revolution that makes antibiotics look like band aids.
- dekhn 5y ago
  It was posed to be a revolution when I started my career, some 30 or so years ago. The pace is glacial. There is no systematic way to deal with this; nearly every disease has its own details, and individuals differ so many treatments have to be personalized. Many of the changes we make, we don't really know how or why they work. I've left human biology and returned to model organisms because the experiments allow for much less ambiguity.
  - ch4s3 5y ago
    Yeah it seems like that was the norm in the past, but it’s looking like CRISPR and it’s successors are shaped to change that. As long as the set of relevant genes is small, and in a small enough number of cells it should be possible to scale up. Genetic degenerative diseases of the eye, sickle cell, and similar show a lot of promise.
chaostheory 5y ago
It’s good news, but it doesn’t mean that there still aren’t more challenges to overcome. I think the article ends on a really important note: “The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low. We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant”

CoastalCoder 5y ago

I was a little surprised that the researcher talked only about stopping disease progression, rather than reversal. Especially for the 7-month old. I assumed that at that age, the brain was still growing / adapting in ways that could work around the earlier problems. But now that I think about it, I've heard that oxygen deprivation during birth can cause permanent impairment.

halukakin 5y ago
Reading the article, I'm not seeing much info on how the results were 7 months old in terms of brain development. At that age, one would expect brain development to improve. I hope the researchers discuss this in more detail in future news.
DoreenMichele 5y ago
For genetic conditions like this one, it's typically a positive feedback loop -- aka vicious cycle -- where the sicker they get, the sicker they get and it accelerates. Stopping the normal progression would be a huge win in its own right.

drran 5y ago

IMAYousaf 5y ago

I don't have anything to add except that for some reason, I viscerally remember the first time I heard of Tay-Sachs disease in a high school classroom through a video about genetics. Something made me feel so disturbed about this one disease above all else because of the seeming hopelessness of the situation coupled with the rampant cruelty of how it kills kids from the inside and seemingly reverses developmental progress. I don't know why I just remember the moment I learned about this, but this is great news. Hopefully this is the first in many such therapies.

photon_lines 5y ago

"The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low. We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. This grassroots approach is a common theme in ultrarare disease research – development and testing are often supported by parents, foundations and federal grants." FYI - if anyone here is interested in helping these kinds of causes, a company called Orchard Therapeutics provides similar treatments and has just signed a historic agreement for reimbursement for treating MLD patients in Europe (you can read more about it here: https://www.globenewswire.com/news-release/2022/02/04/2378990/0/en/Orchard-Therapeutics-Announces-Historic-Agreement-Making-Libmeldy-Available-by-NHS-England-for-MLD-Patients.html https://www.globenewswire.com/news-release/2022/02/04/237899...). Also big discretion: I do have a lot invested in the company and I have incurred significant losses since deciding to invest in it. In the brilliant world of pyramid schemes vested around crypto-coins and NFTs, I don't regret anything and will keep buying more shares to support the dignity of human life.

godmode2019 5y ago

Can someone explain who this works? """ I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier. Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions. In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. """ They use a monkey virus to deliver two mRNA codes to brain cells, the mRNA after being transcribed, tells the brain cells to create HexA to deal with the target enzyme. Okay, I get that much. But how on earth does this work. """ these DNA instructions enter the nucleus of these cells and stay there """ I thought mRNA could not alter DNA and it was by definition broken down after use by the cell, ie short term by definition?

The_rationalist 5y ago
[dead]
dahfizz 5y ago
Plenty of viruses use DNA and not RNA. The virus injects it's DNA sequence into the host DNA. This is why people have "flare ups" of herpes/cold sores. That is a DNA virus, so once the cells are infected they carry that DNA sequence forever, even after the cells divide.
JunkDNA 5y ago
They’re not using mRNA. They are using a viral vector that contains DNA.

The_rationalist 5y ago

[dead]

scott113341 5y ago

I was actually thinking about Tay-Sachs this morning on a walk, after I passed by a church with a billboard out front that says "Christ died for all, even babies in the womb". I learned about Tay-Sachs in high school biology. I think we watched a short documentary on it, as an example of genetic inheritance, and the importance of enzyme function. I remember being so surprised that something so simple (absence of one protein) could be so horrible. A beyond-grim prognosis, and immeasurable/unavoidable suffering for everyone involved. Since then, it's been something that I can't reconcile with the existence of a higher benevolent being. I'm no expert, but it made a lasting impression on me. I'm so uplifted that researchers have made progress on curing this senseless disease.

pyuser583 5y ago
I mean I come from a religious family with a history of genetic illness. I have quite a few relatives who died in infancy. Their lives mattered greatly, and they improved their families lives immensely. I get that it’s hard to see a child who is going to die as valuable, and I don’t judge people who disagree. But the value is very much there, and initial shock of terror and disgust isn’t necessarily a good ethical guide.
- charlieflowers 5y ago
  I don’t think GP is questioning whether those dying infants’ lives were valuable. I think their point is, those lives were valuable, so how could a benevolent, all-powerful creature allow them to suffer and die merely due to a genetic bug.

starchild_3001 5y ago

This is actually the 2nd brain gene therapy research I've seen. In the Phase I trial below, injecting telomerase and klotho AV vectors into CNS/brain was safe and it improved cognitive scores of 5 dementia patients after 1 yr follow up. Interview: https://www.youtube.com/watch?v=i__oZyxgLC0 https://www.youtube.com/watch?v=i__oZyxgLC0 Paper: https://www.linkedin.com/posts/patrick-e-sewell-md-a994774_gene-therapy-for-dementia-activity-6863849206608732160-h9WW/ https://www.linkedin.com/posts/patrick-e-sewell-md-a994774_g... This space will hopefully get very big. Mice lifespans were extended 25-40% (massive!) through similar techniques. See Dr George Church Gene Therapy for more.

UltraViolence 5y ago

Gene therapy is the game-changer which will enable us to eventually cure cancer. I've been proposing that government stop all investment in refining non-gene therapies, such as radiation and chemotherapy, and to plow everything we have into gene-therapy. Cancer is essentially a genetic disease and we can solve it by repairing the faulty genes, just as with Tay Disease.