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‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy (bloomberg.com)
243 points by mzs 35 days ago | hide | past | web | favorite | 31 comments

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.

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.

I just wanted to take a moment to wish your friends, family, and you well.

Hope it works out for you!

Very, very happy for you!

The actual study is here. It's a remarkable achievement: 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.

Would any of this work for auto-immune diseases? Some of them are linked to genetic markers like HLA-B27 and HLA-DR4

Not with this approach. It's easier to add a gene to one cell lineage (in this case, the blood cell forming hematopoietic lineage) than to remove a gene from every single cell in the body.

But there are other strategies in development to help some patients with autoimmune disease. This is one of my favorite papers in that vein: https://www.ncbi.nlm.nih.gov/pubmed/27365313

Do you have to remove a gene from every cell in the body, rather than modify the blood cells so they don’t attack the rest?

Right--see the paper I linked to above for an example of that. Here's a summary article: https://www.cell.com/molecular-therapy-family/molecular-ther...

If you can't access it then shoot me an email at ron gejman at gmail dot com and I'll send you the pdf.

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

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/

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

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.)

Yes of course, but think about gene therapy for far less intrusive health issues.

If more common and widespread health problems are tackled with gene therapy and we wouldn't know the consequences long term (we really don't) then this aspect becomes far more problematic.

Like you, I would also take the gamble if it's a Hail Mary attempt at surviving or making a somewhat normal life possible. But that's not the point I was trying to tackle.

Not all of it is just targeting the right sites - IIUC the last time we tried gene splicing for this, the splices worked, everything looked great for a little while, but the sites had oncogenes right next to them that got activated by the splicing.

I'm hopeful that this is a panacea for this class of problem the likes of which we rarely see, but I will not be surprised if something tragic happens.

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!

thalassemias. Felt compelled to let you know the correct spelling. I happen to know simply because I know the two Greek words for Thalassocracy.

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!

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

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...

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)


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.

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?

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.

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

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.

Maybe mRNA therapy could help your cousin? There are a number of companies working on using mRNA to treat genetic diseases.

> X-linked severe combined immunodeficiency, or SCID

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

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!

Not a ton. This seems like a good backgrounder:


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