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Haemophilia A trial results 'mind-blowing'

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Re: Haemophilia A trial results 'mind-blowing'

#71

Post by aaavl2821 »

mrfusion wrote: post #65
aaavl2821 wrote: post #47

Earlier quoted context omitted.

AAV is the typical vector used for gene therapy. viruses are useful because they have evolved to insert foreign DNA into host cells. nothing humans can conceivably engineer has come close yet to the ability of viruses to do this however viruses have also evolved a lot of bad qualities that cause disease. AAV is nice because 1) it is not known to cause disease, 2) only causes a mild immune response (so the body doesnt…

Why can’t you take immunosuppressants taking the treatment the second time around?

thats a good question, im sure theres a good answer but i dont know it

id imagine the immunosuppressive dose would have to be pretty strong and come with a host of other risks. i know the immunosuppression load for gvhd is pretty heavy, and corticosteroids are not fun drugs

Re: Haemophilia A trial results 'mind-blowing'

#72

Post by frozenport »

king07828 wrote: post #66

This is awesome. I have Crohn's and am looking forward to an eventual cure. One thing I don't understand is why big pharma and VCs seem to focus on rare diseases instead of a gene therapy for changing eye color or hair color. With eye/hair color gene treatments, patients could undergo the therapy multiple times (if desired) and the pool of patients is all humans (not just rare diseases sufferers). This allows for amo…

Sounds hard because you need to first disable existing machinery that makes the natural color

Then what if you want to change?

Re: Haemophilia A trial results 'mind-blowing'

#73

Post by patall »

king07828 wrote: post #66

This is awesome. I have Crohn's and am looking forward to an eventual cure. One thing I don't understand is why big pharma and VCs seem to focus on rare diseases instead of a gene therapy for changing eye color or hair color. With eye/hair color gene treatments, patients could undergo the therapy multiple times (if desired) and the pool of patients is all humans (not just rare diseases sufferers). This allows for amo…

I am sorry for that but to be honest your comment suggests that you do not have tiniest idea of how hard medical research is. Not only are the topics you suggest much more complicated than rare diseases (i.e. we do not know the exact molecular process but they are certainly much more complex and in the case of eye color, entirely developmental, so changing the genetic background would not switch your eye color), but also much more expensive (for these are nonmedical applications and therefore side affects would kill your drug). So we are talking in the order of 10 billion in R&D expenses. And then, unlike in case of orphan diseases, your patents will be weak and the margin will be low (compared to cost).

Re: Haemophilia A trial results 'mind-blowing'

#74

Post by aaavl2821 »

king07828 wrote: post #66

This is awesome. I have Crohn's and am looking forward to an eventual cure. One thing I don't understand is why big pharma and VCs seem to focus on rare diseases instead of a gene therapy for changing eye color or hair color. With eye/hair color gene treatments, patients could undergo the therapy multiple times (if desired) and the pool of patients is all humans (not just rare diseases sufferers). This allows for amo…

the cost of manufacturing a gene therapy would probably exceed what most people are willing to pay for changing eye or hair color. why use gene therapy when colored contacts or hair dye work, and much more easily reversible in case you dont like it?

also, it is incredibly expensive to get a gene therapy through fda trials. there hasnt really been a "true" gene therapy approved in the us yet (excepting car-t), and the first two approved in europe were pulled from the market because they werent profitable even at a price of $1M per patient. thats why these companies go after severe rare disease -- you can charge more for saving a kids life than you could for changing hair color, and you have to charge a lot to justify the expense and incredibly high risk of developing a gene therapy. and with a rare disease, you can go to market with a 20-30 person sales force to cover all patients, whereas to market a hair or eye color thearpy youd need thousands of people calling on every hair salon and eye doctor in the country. as of now, the success rate in terms of fda approval for gene therapy is 0% -- thats an important input in financial calculations.

further complicating things is that you generally cant dose these drugs more than once bc your immune system rejects the vector after the first dose, so you have to get all your economics upfront

Re: Haemophilia A trial results 'mind-blowing'

#75

Post by aaavl2821 »

olegkikin wrote: post #56
test6554 wrote: post #31

This is fascinating! I wonder if something like this could get the pancreas to begin producing insulin. Type I Diabetes is no joke. It could save tens or hundreds of millions per year, not to mention multiple injections per person per day.

Looks like it's happening: "Modified blood stem cells reverse type 1 diabetes in mice" https://www.diabetes.co.uk/news/2017/nov/modified-blood-stem... And type 2 got cured by an extreme diet in 86% of patients: https://sciencealert.com/extreme-diet-reverse-type-2-diabete...

hate to be the bearer of bad news, but there are something like 400+ drugs that have prevented type 1 in mice and another hundred or so that have reversed it. none have worked in people

the most common animal model for type 1, the NOD mouse model, is notoriously bad. studies have shown that loud music cures diabetes in these mice. mice raised in one lab get diabetes differently than mice raised in another. the immune systems of these animals are very fickle and almost any environmental perturberance can change an immune response

Re: Haemophilia A trial results 'mind-blowing'

#76

Post by patall »

shloosh wrote: post #44
Q6T46nT668w6i3m wrote: post #24

Earlier quoted context omitted.

Many diseases are as simple as your eyes being brown vs blue - you simply have or lack particular proteins. I wish it were that simple. :( Eye color, for example, is influenced by a combination of multiple genes. There’s no straightforward eye color gene. Likewise, it’s especially true for diseases when something like “stomach cancer” is actually a dozen different diseases where each is influenced by dozens of differ…

Yes, but for any disease there are a number of known gene polymorphisms that predispose you to the disease. These genes may interact with the rest of your genome in incredibly complex ways, but I bet all it would take to cure a disease in most cases would be to target the one or two most prevalent polymorphisms.

While it may sound easy to change a polymorphism (and even there only for a single base, don't get me started on larger structural variants), do not forget that you have to apply this one single change to 10 ^ 14 cells (or even just 1 in 10000 cells is 10 ^ 10), while evading the immune system and not inducing any detrimental other mutations. For a software developer it always sounds so simple just to fix a single spelling mistake but that really isn't it.

(+ obvoiusly the stuff from the other comments about how hard it is to determine the cause to begin with)

Re: Haemophilia A trial results 'mind-blowing'

#77

Post by tialaramex »

ericb wrote: post #64
alextheparrot wrote: post #5

What a fantastic gateway to show how gene therapy can completely resolve diseases. Many diseases are as simple as your eyes being brown vs blue - you simply have or lack particular proteins. I couldn’t find it on a cursory reading, does anyone know what vector they used to achieve liver sinusoidal cell specificity? My understanding is that many gene therapy studies have used blood cells, which can be pulled out of th…

Is the virus transmissible?

The study did not look at whether family members or other close acquaintances ended up containing measurable numbers of copies of the virus. The patients were tested and the study verified that the (altered) genetic data from the virus was excreted normally.

The virus was deliberately defective and unable to replicate, so the copies made for use in treatment are the only copies that would ever exist. This also ensures that dose control is effective, if the virus could replicate then further copies of the gene would be inserted.

Re: Haemophilia A trial results 'mind-blowing'

#78

Post by test6554 »

baldfat wrote: post #53
aaavl2821 wrote: post #41

Earlier quoted context omitted.

There are lots of people working on regenerative medicine and gene therapy for autoimmune diseases (ive worked with several researchers focused on type 1), but unfortunately the field isnt there yet. hemophilia a is a disease caused largely by deficiencies in one specific protein. massive technological breakthroughs in recent years have enabled scientists to deliver genes to human cells to consistently, accurately an…

Thankfully artificial pancreas are looking like a good option until we can get to curing type 1. Not only does it save the number of shots like pumps we have today, but it can measure the sugar level and keep the swings down to a minimum. http://www.jdrf.org/research/artificial-pancreas/

They seem good as long as the patient's skin is not allergic to the adhesive used to attach it to the body. I know someone who had an insulin pump that worked perfectly except after a day or two, they would get a rash on the skin and the area would swell up blocking the delivery of insulin.

Nothing like all this great technology that could save your life that is foiled simply by the type of glue used by the manufacturer.

Re: Haemophilia A trial results 'mind-blowing'

#80

Post by test6554 »

aaavl2821 wrote: post #75
olegkikin wrote: post #56

Earlier quoted context omitted.

Looks like it's happening: "Modified blood stem cells reverse type 1 diabetes in mice" https://www.diabetes.co.uk/news/2017/nov/modified-blood-stem... And type 2 got cured by an extreme diet in 86% of patients: https://sciencealert.com/extreme-diet-reverse-type-2-diabete...

hate to be the bearer of bad news, but there are something like 400+ drugs that have prevented type 1 in mice and another hundred or so that have reversed it. none have worked in people the most common animal model for type 1, the NOD mouse model, is notoriously bad. studies have shown that loud music cures diabetes in these mice. mice raised in one lab get diabetes differently than mice raised in another. the immune…

Lab mice are truly living in a golden age of medicine!
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