
First human Crispr gene-editing trial gets early approval - jerryhuang100
http://www.wired.co.uk/article/first-crispr-clinical-trial-approved
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jessriedel
> The small study, which has been funded by ex-Facebook president Sean Parker,
> will augment T cells – potentially a way to treat cancer – but will be used
> to see whether Crispr is safe in humans, rather than being used as an actual
> treatment.

This is misleading, right? Yes, it's true that Stage I trials are designed
(and in particular, _statistically powered_ ) to test safety rather than
effectiveness. But that doesn't mean they are making gene edits with no
therapeutic purpose. That would be highly unethical. The gene edits are
definitely intended to be an "actual treatment". It's just that the number of
subjects is so low there isn't any hope of measuring the effect.

~~~
mikeyouse
Typically in Stage 1 trials, they test safety effectiveness by giving doses of
varying size, often times below the level of clinical effectiveness. They also
give these to much smaller populations, usually fewer than 25 people. The main
goal of these trials is to figure out "safety and dosage" \-- so they measure
side effects at each dosage and try to discern interactions with the body.

They'll be especially careful with the CRISPR drugs due to the disasters that
Gene Therapy trials have previously undergone. Most notably, TGN1412 was given
at a dosage about 500x smaller than the safe dosage in animals but caused
almost immediate cytokine storms that nearly killed all 6 participants in the
trial.

~~~
jessriedel
> they test safety effectiveness by giving doses of varying size, often times
> below the level of clinical effectiveness.

OK, good point. But even then there needs to be a reasonable belief that
either (1) the likelihood of clinical effectiveness is nonzero, and is still
worth trying compared to the smaller chance of bad effects, or (2) the same
patient will be able to receive a clinically effective dose in the future
based on the safety information gained testing the smaller, clinically
ineffective dose on them.

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themartorana
I know the people in this trial probably have nothing to lose, but I do wish
there was a way to recognize them (and others like them in similar trials).
There are times when human testing must happen. With civilization-altering
possibilities like this, these people are pioneers whether it works or helps
us figure out why it doesn't and move the needle forward.

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maga
Since T cells do not reproduce by themselves, I presume the effects of
modified T cells will only last until the cells exist in the body. This
reminds me of a question I was wondering about since I heard about Crispr: can
we use this method to make permanent changes in the DNA of grown up humans,
and if so, do we have clear understanding of how to do it?

The thing that puzzles me most is that if we do it by creating some cells and
injecting them, how do we guarantee that these cells replace their existing
unmodified counterparts?

~~~
rgejman
T cells proliferate when they see their target antigen. This technology is
being used without CRISPR in a number of clinical trials. See here:
[http://www.cancer.gov/about-
cancer/treatment/research/car-t-...](http://www.cancer.gov/about-
cancer/treatment/research/car-t-cells)

~~~
maga
Thanks for the correction, I didn't know T cells multiply by themselves. Yet I
assume they don't hang around permanently and will be sooner or later replaced
by new, unmodified, cells produced by the body, hence, why I was asking about
making permanent changes.

~~~
rgejman
Maybe. We haven't been doing this long enough to know. T cells can divide into
a T "memory" type, but I'm not sure if CAR-T cells do this.

