
Early results boost hopes for historic gene editing attempt - rbanffy
https://www.apnews.com/2543a04b925c443b9ad3987f4209e68e/Early-results-boost-hopes-for-historic-gene-editing-attempt
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hprotagonist
On the other hand, their stock price just took a solid hit.

Derek Lowe goes into why:
[http://blogs.sciencemag.org/pipeline/archives/2018/09/05/san...](http://blogs.sciencemag.org/pipeline/archives/2018/09/05/sangamos-
gene-therapy-results)

 _There are only two patients that we’re talking about here. But both of them
showed significant declines in the heparan sulfate and dermatan sulfate in
their urine, which is good news. However, and this is where the arguing really
revs up, they could not find any IDS enzyme in the blood of these patients.
You’d have kinda thought that you’d see it there (they sure saw it in the
animal studies), and a lot of observers /investors sort of lost it at that
news, sending SGMO down pretty briskly in the early trading today. The company
responded by saying that there had to be new active enzyme in there for the
urine numbers to go the way that they did, that their detection method isn’t
incredibly sensitive to start with, that there’s another cohort in the trial
that’s getting a larger dose of the gene therapy, etc.

Of course, they also said that urinary levels of GAG were an approvable
biomarker and that’s how the enzyme replacement therapy was approved, and that
appears not to be true. The enzyme (Elaprase, from Shire) showed effects in
the amount the treated patients could walk and the trials looked at lung
function as well. In the end, you’re going to want to see functional
improvements in these patients anyway, but everyone’s looking for an earlier
read. The selloff in Sangamo’s shares continues as of this writing, and other
gene-editing stocks are dropping as well (and since these are all companies
using different gene-editing technologies, that seems a bit like panic if you
ask me). But this can’t have been the way that Sangamo wanted this to go. When
that next cohort reports, maybe we’ll have a better idea of what’s going on –
either that, or the shouting will get even louder. . ._

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candiodari
This is gene editing on a large scale, but they suggest that they're
"permanently changing someone's DNA", which is true, and it's false. It's
pretty inaccurate.

The issue with Hunter's syndrome is that the body refuses to produce a set of
enzymes that break down certain sugars, resulting in a buildup, resulting in
complications, resulting in death.

In order to fix it, they're going to use a virus that inserts a new gene that
produces the breakdown enzymes in a large number of cells, up to hundreds of
thousands. Large numbers however only in absolute terms. If compared with how
much cells they have we're talking one in a million or even less cells of
their body.

Because this will cause those cells to produce those breakdown enzymes, which
will then spread through the body and do the work, this should work to treat
the disease. But there's a lot of caveats:

They're introducing a new gene indiscriminately. They're not fixing the
existing gene.

Also they're only "converting" a relatively tiny amount of cells. Enough so
the treatment sticks (ie. it needs to infect stem cells), but certainly not
all. Even so, it is expected the effects of the treatment will grind down over
time, maybe requiring regular treatments, at an unknown rate.

Procreation cells, in both men and women, are protected against viruses
through special mechanisms. The virus will not be effective on them, and
therefore their children will at least be carriers of the disease and
potentially need treatment themselves.

The sad thing is what these treatments will lead to over the long term. If we
treat many people for metabolic diseases, genetic diseases will "spread". The
diseases are currently limited from spreading because they are at an
evolutionary disadvantage: infected people die before having kids. If that's
fixed, there will be increased rates of genetic defects in children.

Eventually this may lead to very few human babies being born without metabolic
disease and nearly everyone being dependent for their life on treatments like
these.

Of course, that's a long term potential consequence. It would not be moral to
not treat these people. And of course, in the future it may be possible to
target procreation cells as well, and we probably should.

~~~
rbanffy
I'm assuming it won't take more than a couple decades for someone to invent a
way to fix the specific gene and do that in reproductive cells. With IVF and
embryo selection, the undesired trait can be selected against. In Brazil (I
lived there) you are allowed to search for genetic traits in embryos and
select the ones for implantation based on that. The only trait doctors are
forbidden to disclose is sex.

