
Approving a Muscular Dystrophy Drug Ignites a Civil War at the FDA - adenadel
http://www.forbes.com/sites/matthewherper/2016/09/20/approving-a-muscular-dystrophy-drug-ignites-civil-war-at-the-fda/#38899d54353d
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mikeyouse
Derek Lowe -- Of the fantastic "In The Pipeline" blog with Science disagrees
with the FDA approval;

[http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sar...](http://blogs.sciencemag.org/pipeline/archives/2016/09/20/sarepta-
gets-an-approval-unfortunately)

He's an excellent read if anyone wants to keep up with things in the Pharma
and regulatory world. He's probably more famous for his "Things I Won't Work
With" series that I've seen linked to a few times on HN.

> And he’s just getting warmed up, if that’s the right phrase to use for
> something that detonates things at -180C (that’s -300 Fahrenheit, if you
> only have a kitchen thermometer). The great majority of Streng’s reactions
> have surely never been run again. The paper goes on to react FOOF with
> everything else you wouldn’t react it with: ammonia (“vigorous”, this at
> 100K), water ice (explosion, natch), chlorine (“violent explosion”, so he
> added it more slowly the second time), red phosphorus (not good), bromine
> fluoride, chlorine trifluoride (say what?), perchloryl fluoride (!),
> tetrafluorohydrazine (how on Earth. . .), and on, and on. If the paper
> weren’t laid out in complete grammatical sentences and published in JACS,
> you’d swear it was the work of a violent lunatic.

[http://blogs.sciencemag.org/pipeline/archives/2010/02/23/thi...](http://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride)

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pcvarmint
This article has many scientific gaffes:

 _because the genetic defect that causes Duchenne is on the X chromosome, it
is a disease of boys._

It is because it is an X-Linked-Recessive trait that it a disease of boys.
Saying "because [it] is on the X chromosome" adds no value by itself. If it
were "because [it] is on the Y chromosome", then it would sufficiently follow
that it was restricted to boys (with rare exceptions).

 _The data showed an increase of only 0.28% of normal levels, which was, on
average, a tripling of dystrophin levels for these boys._

I have no idea what to make of this. "Increase of only 0.28%" == "on average,
a tripling"?

 _Unger was worried about the unknown risks of the drug, as well as the risks
to boys who might get injection ports while they were also on immune-
suppressing steroids, raising the risk of_ injection (sic).

~~~
Declanomous
I don't see an issue with the statements that were made.

An increase in dystrophin levels to .28% of normal levels, indicates that
without the drug, the dystrophin level was at .093% of normal levels. (.093% *
3 = .28%) The drug succeeds at raising dystrophin levels, but the levels are
still well below those of a healthy individual. (Which is the center-point of
the whole debate)

A recessive x-linked trait will be more likely in men than women, because men
have one x chromosome, and women have two. This means that a male with an
x-chromosome with the Duchenne gene will always have Duchenne, whereas a woman
would need a copy on each of her x chromosomes, assuming the woman isn't XY
with androgen insensitivity, or XXY, etc.

A common example of an x-recessive trait would be colorblindness. Genetic
colorblindness affects about 8% of men and .5% of women. Since men always have
colorblindness if they carry the gene, we can use the prevalence in men as the
population prevalence, assuming colorblindness doesn't play a role in sexual
selection (doubtful, given the fact that fashion sense probably plays a role).
.08 _.08 = .0064, which is pretty close to the prevalence of colorblindness in
women.

Duchenne affects 1/3600 men. Assuming 1/3600 is the prevalence of the gene in
the population, we'd expect 1/3600 _ 1/3600 = 1/12960000, or 1 in thirteen
million women to have it. So we'd expect about 25 female cases in the US, and
about 83000 male cases.

Edit: This is assuming having two Duchenne genes will still lead to Duchenne.
If 3x normal levels of dystrophin leads to clinical relief, it's possible that
having two genes allows for enough dystrophin production to prevent Duchenne.
I don't know enough about the pathways involved, but it's possible.

