
Three people with inherited diseases successfully treated with CRISPR - leonnoel
https://www.newscientist.com/article/2246020-three-people-with-inherited-diseases-successfully-treated-with-crispr
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tialaramex
It's interesting that they did _not_ just undo the inherited disease. I
assumed that, especially with Sickle Cell where we have a good understanding
of how it works, they would go into Chromosome 11 and put it back how it
"should" be with CRISPR. But instead they apply a workaround, ensuring
continued fetal haemoglobin production.

The article does not mention whether that's because putting Chromosome 11 back
with CRISPR is harder, or whether for some reason that wouldn't fix the
problem.

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Roritharr
That's also what struck me as odd, but having maintained legacy systems for a
long time I can see why it's sometimes preferable to use a proven if inelegant
workaround than going in and try to fix the actual defect, especially if you
have limited debugging options.

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dogma1138
Analogies to IT and development aren’t that appropriate here tbh.

This isn’t a legacy system, if you want to keep the IT analogy this would be
failing over to a different system or replacing an existing solution that
doesn’t work with a competitive alternative rather than fixing all your bugs.

~~~
Roritharr
This wasn't meant very serious, i'm sorry I couldn't indicate that better. I'm
in no way,shape or form qualified to chime in on this topic.

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Roritharr
This is such mind-blowing success, it makes me contemplate switching fields.
Is it reasonably feasible to switch from IT to Biotech/Medical Research in the
mid thirties?

I had a friend with Fukutin-related limb-girdle muscular dystrophy R13 and am
wondering if CRISPR could be the solution for her.

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akkawwakka
It’s worth knowing there are very few diseases that can be cured with singular
gene edits. Many diseases involve multiple genes, cascades of gene expression,
or complex physiological pathways. Oh, and not to mention epigenetics and
environmental factors.

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loeg
My family has one of the well-known single-site cancer-causing mutations; we
know what the specific site is, even. It would be immense to "fix" (I am not a
geneticist) that single site. Even just for my kids.

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sszz
Why would you prefer the risks of editing versus the risks of preimplantation
screening? Editing would be strictly riskier unless there’s really no
alternative (unlikely but possible)

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loeg
Preimplantation screening isn't an option for me or any other of my family
members who are long past implantation. I'm not saying I'd hop on stage 1
clinical trials of a potential editing cure, and we'd have to see what the
data on risk looked like to compare it with the risk from cancer without
editing.

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34679
>The remaining bone marrow cells are killed by chemotherapy, then replaced by
the edited cells.

Interesting that they need to kill the remaining bone marrow cells. I wonder
what happens when they skip that step. Do the modified cells still reproduce,
resulting in a partially effective treatment? Are they targeted by the immune
system and eliminated? Are they just out-reproduced by the normal cells and
fade into irrelevance?

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refurb
If you don't kill off the existing bone marrow, you end up with a couple
problems:

1\. You only give the patient a small number of edited cells. You want those
cells to multiply and replace the existing cells. If you don't remove the
existing cells, the edited cells aren't going to reproduce very fast because
the body has a feedback loop and is saying "we have enough bone marrow cells
now, so no need to make more".

2\. Host versus graft disease. The old immune system will attack the new
immune system cells.

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enchiridion
Do these patients have to be revaccinated?

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refurb
I’m not a doctor, but I would say yes, you’d lose any acquired immunity since
you kill off all the memory b-cells that store that information.

But you’d also gain the donor’s immunity, and if they’ve been vaccinated, the
recipient would have that immunity as well.

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rnet85
That is not correct. Trained B cells are predominantly stored in lymph nodes.
You also don’t gain host immunity by marrow transfer.

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enchiridion
So B cells are what responsible for learned immunity?

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surfsvammel
Smalll thing, Beta thalassaemia isn’t a disease — as far as I know. It’s a
disorder or a syndrome.

Definition of disease: Resulting from a pathophysiological response to
external or internal factors.

Definition of disorder: A disruption of the disease to the normal or regular
functions in the body or a part of the body.

Edit: I have it myself (and my kids do too), and I often correct people on
this. Since I rather have a disorder than a disease:)

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MeteorMarc
Note that this only edits the bone marrow cells, it is totally different from
the scandalous experiment on gene editing in human embryos:
[https://www.livescience.com/64166-first-genetically-
modified...](https://www.livescience.com/64166-first-genetically-modified-
babies-risks.html)

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im3w1l
Fetal hemoglobin binds stronger to oxygen than normal hemoglobin, so that a
fetus can "steal" oxygen from its mother's blood. But if the mother has been
crispred to also have fetal hemoglobin, then this won't work right? Meaning
it's a male only treatment?

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sandworm101
Means that it is a treatment for anyone not able to have children, which is
about half of females (post-menopausal, plus other infertilities).

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williamdclt
Add to that all women willing to give up the ability to have children for the
treatment, which might be sizeable

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sandworm101
Because of accidental pregnancies, there are some treatments denied to all
fertile women regardless of choice. Ussually they are those that cause
horrible birth defects (limb reductions etc) or make pregnancy deadly to the
mother. Given the links between oxygen and injuries like FAS, this hemoglobin
treatment may be one of that group.

Example: Acutane was once used to treat acne in teenagers. Many/most doctors
didnt give it to teenage girls regardless of whether they were sexually active
or on the pill. Mistakes happen. That drug would do horrible things to a
fetus.

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BurningFrog
For acne, I support this policy.

For serious conditions like those in the article, forcing sterilization seems
real cruel in an age with safe and plentiful abortion.

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alistairSH
_safe and plentiful abortion_

Not in the US.

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dghughes
I like how evolution if you can call it that figured out first that fetal
haemoglobin mitigated the problem.

The fix used CRISPR (and a gene engine?) to implement the fix on other people.

It's like version 2 of what human bodies figured out first naturally.

This sounds like something that my dad or other people with COPD/IPF could
use. If fetal haemoglobin could grab more oxygen it would benefit people with
low lung function. Sort of like Star Trek "Trioxin" they loved to use.

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dogma1138
I wonder since fetal hemoglobin has stronger binding with oxygen which means
the blood can oxygenate faster if this can be used for other issues as well
like reduced lung capacity and performance enhancement.

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percutaneous
Yes but it also holds onto oxygen more tightly, making it difficult to
released to cells that need it. There's no performance enhancement here.

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crimsonalucard1
I'm hoping that other then treating diseases this thing can aid with
enhancement.

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Paperweight
But will the drug approval agencies allow genetically engineered therapies for
anything disruptive? For example, they've been blocking the caries vaccine for
decades.

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shock
> blocking the caries vaccine for decades

Please give more details.

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dogma1138
There are no details to give, there never was a successful caries vaccine it’s
just always been stuck at being worked on.

Big dental isn’t blocking it we just don’t have a good enough model and yes
there isn’t a sufficient financial incentive to develop it really either.

Caries isn’t a big problem these days, it’s not then major cause of tooth
problems as people grow older, dental hygiene and more importantly fluoride in
water pretty much solved it for those population that were affected.

There is no financial reason to block a caries vaccine as it’s not going to
have any impact on the industry, cosmetic and corrective procedures would
still be just as in demand and gum disease is by far a bigger factor for tooth
loss in adult patients than caries.

Not to mention that quite a lot of the “vaccines” weren’t traditional vaccines
but rather replacement therapies where lacto acid producing bacteria would be
replaced with strains that cannot produce it but can outcompete the
lactobacillus flora in your mouth, these treatments are let’s say problematic
since we have had little to no experience in flora replacement therapies and
can’t predict or model the outcomes well.

