[meese712]

I'm confused how this would reduce disease progression compared to a much cheaper allo bone marrow transplant then if they are only modifying hematopoietic stem cells since a BMT is just doing the exact same thing except with someone else's non affected cells. BMTs are a horrific procedure though so this definitely has an advantage in that regard.

I would also have to imagine they would have to do myeloablative chemo or radiation to make sure the fixed cells propagate more than the diseased cell line.

Edit: read the study, they do give them the same chemo used for normal transplants.

[piyh]

Most recipients don't need to take immunosuppressants at all if they get PBSC or bone marrow transplants. Even if they do, it's short term. Additionally, the allo grafts need to be matched, which if you're non white is not a good success rate. 85%ish of whites get matched, that number gets depressingly low for minorites. On the US registry, only 1 in 400 donors get called. I happen to be one of those donors and a system where I'm not needed is a better one. The best part is no part.

https://ashpublications.org/blood/article/104/12/3501/89040/...

>Previous studies have shown that 30% to 70% of all patients surviving beyond 100 days after HCT require treatment for chronic GHVD,2,4-6 often for more than 2 years.

Re: a better system is where you don't need donors:

https://www.cbsnews.com/newyork/news/l-i-woman-dies-after-ma...

[concordDance]

> 85%ish of whites get matched, that number gets depressingly low for minorites.

Hmm...

How does this translate to other places? E.g. can you only match Han in China?

Do Italians and Scots match? Turks and Egyptians?

[mlyle]

A big part of the problem is that minorities are not reached/enrolled onto the registry at a high rate.

What matters isn't really the proportion of the subpopulations that are registered, but the absolute numbers.

[inciampati]

Matching involves the now simple (if costly) task of comparing diplotypes at immune system loci involved in self recognition, like the MHC.

What's horrific to me is that matching by race is still a thing! These genes are under diversifying selection. That means that they often do not match the surrounding genetic background. That means that racially driven matching is bonkers.

[meese712]

I was getting at the article giving the impression this somehow cured the disease vs a BMT just slowing progression. I know the whole transplant thing sucks. I've had two transplants, thank you for being on the list :).

[tialaramex]

The article indicates they don't know. "it is not yet clear whether it will persist life-long, and extended follow-up is needed" - So they can be optimistic without knowing for sure because they don't have a bunch of kids they treated say ten years ago to check on. It seems like this might stick, they hope it will, they can't know yet.

One of my friends gave his wife a kidney which allowed her to get off dialysis, so yeah, thanks to anybody who is willing to do this for someone they don't even know.

[jimbob45]

What’s the story with minorities? Just a smaller pool of donors or something?

[jonfromsf]

Yes, a smaller pool of donors. Worst still for finding matches is multi-racial people.

[Gatsky]

Reading the paper [1], the genetically modified stem cells overexpress the ARSA enzyme. This seems to create a ‘bystander effect’ which increases the total body enzymatic activity above some critical threshold sufficient to arrest the disease process. Myeloid cells associated with neuronal structures are probably critical to this benefit. A standard bone marrow transplant doesn’t reach this threshold, and has demonstrated poor efficacy in early onset disease.

[theGnuMe]

Well it removes graft vs host complications which is a win and the requirement to take immunosuppressants for life.

[meese712]

Definitely true GVHD sucks. The article gave me the impression that they were saying it was somehow superior at stopping the disease because it said this "stem cell transplants, have sometimes been used to slow the disorder's progression in infants,"

(fyi a decent amount of stem cell transplant survivors do not have to take immunosuppressants for life)