
‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy - mzs
https://www.bloomberg.com/news/articles/2019-04-17/-bubble-boys-cured-in-medical-breakthrough-using-gene-therapy
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scop
I am an adult living with a primary immune deficiency and this is quite
surreal. Dr. Jennifer Puck, on the left in the photo, is my doctor at UCSF.
Let me just say that she is an incredible doctor.

I’ve had a vague hope in gene therapy for many years, but have never really
believed I would live to see it come to market as a real treatment.

I’ve told my family many times that “maybe gene therapy will be the fix”.
Today is the first day I’ve actually believed those words.

~~~
Scoundreller
Although it may be a first for this specific SCID (X-linked), there are other
SCID forms that have successfully been using this gene therapy approach for a
little while.

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rgejman
The actual study is here. It's a remarkable achievement:
[https://www.nejm.org/doi/full/10.1056/NEJMoa1815408](https://www.nejm.org/doi/full/10.1056/NEJMoa1815408)

No CRISPR/Cas9 was used in this study.

We'll have to wait and see if any of the patients develop hematologic
malignancies (blood cancers).

I predict we'll see dozens of papers like this in the next few years. Sickle
cell and thalessemias are low hanging fruit.

~~~
Scaevolus
CRISPR has much better targeting than lentiviral gene editing, so it should
have much lower rates of cancer too.

~~~
neuronic
The incredibly vast sphere of gene-to-gene interactions is very poorly
understood.

Anything changed in the DNA can have completely unforeseen consequences
because genes and their products influence expression of other genes.

Which genes does each gene influence? Directly or indirectly? To what extent
(strength of up- or downregulation)? Only under specific conditions? Only if 3
other genes are present and not regulated in a different manner?

I have done some computational gene interaction analysis by building
regulatory interaction networks in Cytoscape using sequencing and expression
data based on specific research [1].

My subjective impression is that messing with genes is little but an
unpredictable endeavor at this point. The gamble may pay off but I don't think
anyone can honestly tell you something about long-term effects in each
individual.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503487/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503487/)

~~~
lawlessone
I think i'd take the gamble over living in an isolation room for my entire
life

~~~
MrEldritch
It doesn't really matter whether you would or would not take the gamble; it
depends on whether the FDA would be willing to let you.

(I'm not saying this as some kind of rrrgh-gubmint-bad thing. It's pretty
normal for the government to have authority over what gambles are acceptable
to offer in what circumstances, and which ones are exploitative and
detrimental to even offer; this is the logic behind, for instance, regulations
of _actual gambling._ )

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ethagknight
St Jude is an amazing place. All patients treated for free. Incredible
research taking place funded by charitable donations.

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folli
The pricing issue of gene therapy is quite interesting. A comparable treatment
which is licensed now (Zolgensma, Novartis), has an estimated price tag of $2
million [1].

[1] [https://www.bloomberg.com/news/articles/2019-04-07/gene-
ther...](https://www.bloomberg.com/news/articles/2019-04-07/gene-therapy-was-
hailed-as-a-revolution-then-came-the-bill)

~~~
s1artibartfast
Interesting indeed. Would you say that this is price is unreasonably high? If
I am reading the following article correctly, the target patient population
for Zolgensma experience an average of 4.2 hospitalizations a year with a mean
cost of $150K per hospitalization (2012 dollars and rates)

[https://link.springer.com/article/10.1007/s41669-018-0093-0](https://link.springer.com/article/10.1007/s41669-018-0093-0)

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DoreenMichele
This is great news. But it says they've licensed it to a small pharmaceutical
company, whose shares are now up 400%.

There are a number of "miracle cures" out there for genetic disorders that
have been effectively discontinued or that have insanely high prices. I'm
concerned that future articles about this breakthrough will be in that vein.

Hopefully not, but that's my fear.

~~~
minhaz23
How does that work? Why license to a small company instead of selling
yourself?

Also, how are people aware of these small pharmaceutical companies and future
breakthroughs like this without insider trading? Meaning, some people profited
handsomely on this deal, how did they make it happen if not luck or insider
trading?

~~~
DrAwdeOccarim
You're asking a lot of important questions and I'll take a stab at answering
them.

The discovery of a new molecule or invention of a new method for treating
disease is about 5-10% of the effort required to bring a drug to market. Yes,
it's clearly not possible to bring a drug to market if it has not been
invented, so it's essential to the process, but the difficulty shepherding
this new thing through to commercial approval is fraught with difficulties.
Universities and hospitals don't have the right talent to do this, nor do they
have the resources or the risk tolerance so they sell some of the future gains
to a company through licensing for money now. This is how almost all drugs are
developed now-a-days, through licensing deals from the inventing parties. This
brings the drug to market a lot faster, helping patients more quickly, and
reduces the risk of development failure which would prevent patients from
getting the drug.

On your second question, the biotech space is small and the number of
investing analysts are also small in number. This means you can get a sense of
the entire space by following a handful of people on twitter or by email. If
you're in the business, you knew who's working on what. Biotech is unlike
high-tech in that you need capital to do the work. Making an app can be done
by a single person in their apartment. Making a drug requires millions of
dollars, special lab equipment, the right people, being in a hub, etc.

In terms of insider trading, the SEC has strict rules on trading on non-public
information and compartmentalizing this kind of information to a small group
of people who have their trading accounts basically always watched by
regulators. Every year a number of biotech employees go to jail for insider
trading, so it clearly happens but the SEC is really vigilant on pursing it.
The people who profited from this are likely the employees of the company and
the investors. They didn't need insider trading as much as they needed to be
in biotech, live in the Boston area, want a job working on gene therapy, and
work for the company. It's like asking how did people make money off Facebook,
or any other company that started-up and made it big.

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seibelj
This is absolutely incredible!

Does anyone know if this can help GSD? My cousin has it and it’s an absolutely
horrible disease, her childhood was robbed and her parents' lives upended
[https://en.m.wikipedia.org/wiki/Glycogen_storage_disease](https://en.m.wikipedia.org/wiki/Glycogen_storage_disease)

~~~
Scoundreller
My guess is that it would be difficult because you have to kill off/weaken the
existing problematic cells to allow the new ones to take over with these
therapies.

This is manageable when you’re treating a white blood cell disease as you can
live temporarily without these cells and they regenerate frequently.

But if all you need are some cells to produce more of an enzyme and can
produce it in sufficient amounts to manage the existing cells producing the
bad enzyme, you might be in luck.

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Scoundreller
> X-linked severe combined immunodeficiency, or SCID

This is poor phrasing. There are non X-linked SCIDs.

~~~
minhaz23
What's your level of experience with this subject?

Where can I learn more about gene therapy as well as CRISPR/Cas9?

Specifically seminal papers?

Where can I learn more about the business aspect of it? Industry, projections,
opportunities, etc.

Thanks in advance!

~~~
Scoundreller
Not a ton. This seems like a good backgrounder:

[https://primaryimmune.org/treatment-information/stem-cell-
an...](https://primaryimmune.org/treatment-information/stem-cell-and-gene-
therapy)

