First gene therapy for Tay-Sachs disease successfully given to two children
theconversation.com
theconversation.com
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.
I've left human biology and returned to model organisms because the experiments allow for much less ambiguity.
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”
I’ve always had a passing interest in this subject. Will be cool to know how folks are systemizing this field
As I said i'm not an expert, just a first year student getting my mind blown.
But in my classes, we look at catalogs of genetic vectors:
here's a top google hit https://en.vectorbuilder.com/
These vectors contain a number of indicator genes, such as antibiotic resistance, so you can use the antibiotic to kill the bacteria that didn't take up your vector.
The vectors have a prepared insertion site to take your gene, that's right in the middle of another gene that produces a colored product.
If the your resultant bacteria produces the colored product, you know you gene didn't make it into the insertion site or it would have broken that gene.
There's vast catalogues of this stuff.
Then when you want to do full genetic sequence to see where your gene has inserted, that's pretty much automated for you.
https://www.thermofisher.com/au/en/home/life-science/sequenc...
You want to compare the genetic sequence to other organisms, there are online search engines for that:
https://blast.ncbi.nlm.nih.gov/Blast.cgi
If your experience is anything like mine, once you start searching for this, google ads is going to lure you into the rabbit hole with offers to 'automate your agrigenomic high throughput whole sequence workflow' and 'rapid de novo genome assembly'
Some of the stuff google is trying to sell me, seems only slightly more non-fictional than 'mystery flesh pit national park', which is of course a searchable phrase.
The problem is figuring out how to pay for such things to begin with.
In the United States today, approximately 1 in every 27 Jews is a Tay-Sachs carrier.
https://healthresearchfunding.org/17-good-statistics-tay-sac...
One day it's "we should save these kids from a difficult life," the next it's "we need symbols to tell undesirables apart," the next it's "we have too many people in camps and nowhere to send them." People like me ended up in those camps next to the Jews, so I'm not keen on the noise that starts the landslide.
That's a fact. And it's only going to be more of a fact the deeper we dig into our genetic code.
But it's how we respond to and deal with that that determines whether we commit good or evil.
We both know that will never happen. They’ll never “deal with” the flaws in their religion, they’ll just ignore it like all the others do.
Just calling every genetic screening designed to prevent actual suffering eugenics is pretty nonsensical.
It's also putting words in my mouth since I said no such thing.
My litmus test for eugenics requires an ideological and social engineering component.
Simply telling parents well if you bring a child to the world they’ll die within 2 years and suffer greatly isn’t that. Neither is offering them other tools such as using a sperm or egg donor or adoption.
I agreed with a reply to that suggesting such an extreme and unnuanced statement amounted to eugenics since the only means to actually ensure that no child will ever be born with X genetic disease would require rather extreme measures that go far beyond providing testing and options.
I really shouldn't smoke. I don't endorse SS officers killing me if I do.
And regarding eugenics they only screen for diseases that require two carriers, because such a person can marry someone who is not a carrier. Diseases that manifest with a single copy of the gene are specifically not screened for because there's nothing the person can do in that case.
It’s also not wrong, if we’re being totally honest.
Things are either eu (beneficial) or dys (harmful) genic.
The bottom 75% of the IQ curve has been poisoned against the word “eugenics” to the point that they can’t even have a basic conversation about things as sane as “genetic screening for debilitating illness” without completely breaking down.
This is a really not good way to engage with this topic. I'm not happy seeing this kind of framing on HN of what is an extremely sensitive topic for many people and with good reason.
That said I expect that in the future, for many genetically inherited diseases, parents will be given the option to address the problem without termination, so long as the solution seems to be exceptionally safe and highly effective (IE, 99.999% confidence the outcome will be positive). I don't think people will see that as "eugenics", although there have been a few press campaigns that have done so.
That's...an understatement.
> Everyone who tried it thought they were doing their victims a favor.
No, not everyone who did it thought that they were doing their victims a favor. Quite a lot saw their victims as people who ought to be sacrificed for the good of others, and if they thought they were doing them a favor it was only in not murdering them outright as well as preventing them from reproducing.
Of course, some eugenics practitioners didn't bother avoiding outright murder, e.g., the Nazis.
2. Assuming you’re referring to the fact that being a carrier is more common in Ashkenazi Jews, you’re aware that there are a number of genetic screening programs run by Jewish organizations, right?
Also, literally everyone is a carrier of mutations for extremely devastating diseases. You just do not know which ones.
This is from a US government website covering Tay-Sachs (https://www.genome.gov/Genetic-Disorders/Tay-Sachs-Disease):
“While anyone can be a carrier of Tay-Sachs, the incidence of the disease is significantly higher among people of eastern European (Ashkenazi) Jewish descent. Approximately one in every 27 Jews in the United States is a carrier of the Tay-Sachs disease gene. Non-Jewish French Canadians living near the St. Lawrence River and in the Cajun community of Louisiana also have a higher incidence of Tay-Sachs. For the general population, about one in 250 people are carriers.”
Traced back to a single particularly fecund Jewish ancestor I believe.
Genetic testing can identify carriers, so if Tay-Sachs has been (mostly) 'vanquished' from the Ashkenazi community, it can be 'vanquished' completely.
https://www.nytimes.com/2003/02/18/science/using-genetic-tes...
The OP’s point was clearly (to me) that genetic diseases like this should be eliminated at the embryo stage.
What does you going all “Jews” have to do with anything?
That’s not clear. In the past Tay-Sachs was prevented mostly by pre-marriage genetic counseling.
Fortunate! That's very fortunate!
> rational eugenics
No such thing unless your basis for it is incomplete or corrupted.
You could say this counts as Eugenics, but maybe people just need a different word since Eugenics is so tainted.
I think if there was a test for Down's syndrome and a gene therapy cure, that would almost certainly be deployed, and advocates for people with Down's aren't going to have a big problem with that. People learned from the autism speaks debacle.
And of course we mustn't forget the reaction to He Jiankui, who claims to have created the first permanently modified humans, and the response in China was to jail him and fine him. It's not just the West.
Gene therapy done in a medical setting where society has had a chance to understand what's going on isn't really eugenics, or is a form that isn't "bad". It's different from "sterilize the defectives" and "X people are Yer then Z people", especially because the people doing this have consulted extensively with bioethical experts and have also subjected their plans to scrutiny by the larger society.
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/2022/02/04/237899...).
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.
Wish this were not the case.
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.
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.
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.
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.
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.
Stopping the normal progression would be a huge win in its own right.
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
Paper: 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.
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.
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.
""" 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?
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.
Cancer is essentially a genetic disease and we can solve it by repairing the faulty genes, just as with Tay Disease.