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Haemophilia A trial results 'mind-blowing'

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Re: Haemophilia A trial results 'mind-blowing'

#101

Post by Nomentatus »

todd8 wrote: post #50
soperj wrote: post #33

Earlier quoted context omitted.

Doesn't make much sense when my eyes were blue as a kid, but now are green except for a quarter of one eye which is brown.

Brown, green, hazel eye colors are variations in the amount on melanin in the iris. This amount can change as one gets older. Babies can have lighter eyes that become darker. Blue eyes are believed to be caused by an isolated, inherited gene, OCA2. This gene is present in all people that have blue eyes. It disables the production of melanin in the iris. All blue eyed people are believed to have a common ancestor from…

It's likely not harmless but very positive to spread so quickly. I think one hypothesis is the domestication of dogs. They don't usually track fingers, but they do track eyes and having blue eyes may help there. There are many types of melanin - I believe the gene only cuts out one kind.

Re: Haemophilia A trial results 'mind-blowing'

#102

Post by MBCook »

jlg23 wrote: post #83
Brakenshire wrote: post #81

Earlier quoted context omitted.

> Unfortunately, our disease-specific drug approval process does not scale and prevents us from realizing the benefits of these techniques and technologies. On the other hand, something which is exceptionally well known to work should also attract huge and immediate capital to do the proper tests. Even for rare diseases, a sure thing would be funded. I think the difficulty is more about procedural or cell based cures…

> Even for rare diseases, a sure thing would be funded. Only if there is a ROI. Which also means that even treatments for not-so-rare diseases don't get funded if the majority of patients won't be able to afford the treatment at a price that provides that ROI. Clinical trials in the US or Europe are insanely expensive and you cannot even budget them: Adverse reactions by "male patients over 45, born on a new moon Tue…

But for an insurance company, the ROI on curing someone’s hemophilia may be very very large.

On the more consumer side of things, being able to fix some sort of obnoxious but perfectly survivable condition that genetic engineering may be able to solve (say lactose intolerant) may be something that you could sell to a lot of people.

Re: Haemophilia A trial results 'mind-blowing'

#103

Post by [deleted] »

Chriky wrote: post #19
seren wrote: post #12

Earlier quoted context omitted.

> I think if this worked as intended, no additional treatment is required. It is correct if the therapy is targeting all stem cells. I have not understood clearly from the article but it seems the treatement is targeting "living cells". Once all your 'fixed' cells have been renewed you would need another round of treatement.

I have Haemophilia A, I was actually offered a place on an earlier trial although I didn't do it. It was explained to me that you would not need further gene treatments even though it targeted adult cells. I think most cells are made by mitosis and don't come from stem cells. Here's a screenshot of the explanation I received when I was invited on the trial - https://i.imgur.com/H329Vgv.jpg > "By using BMN 270 to prov…

[deleted]

Re: Haemophilia A trial results 'mind-blowing'

#104

Post by Nomentatus »

dekhn wrote: post #51
shloosh wrote: post #44

Earlier quoted context omitted.

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.

"You bet"? This is one of the core questions in human genomics/health research today and nobody has been able to make a convincing argument in general that your proposed approach would work.

Would you agree: The question being specifically whether in most cases necessary-even-if-not-sufficient genetic traits can be found ("genetic traits", as opposed to "genetic illnesses" since illness may not be the most likely result.) The problem being that although so far most of our exciting findings are of at-least-necessary genes (or plural genes, etc); obviously it's just these sort of cases that will produce high correlations and grab attention, so there should be a presumption of the equivalent of "publication bias." Necessarily, these will be the low-hanging fruit even if such cases are actually the exception, overall.

Of course, mere and relatively small correlations between disease and genetic traits are extremely common; but there are lots of possible explanations of such findings. In some cases 16 percent of all genes have a small positive correlation to a given disease, and "if everybody is at fault nobody is at fault!"

Re: Haemophilia A trial results 'mind-blowing'

#105

Post by kgwgk »

MBCook wrote: post #102
jlg23 wrote: post #83

Earlier quoted context omitted.

> Even for rare diseases, a sure thing would be funded. Only if there is a ROI. Which also means that even treatments for not-so-rare diseases don't get funded if the majority of patients won't be able to afford the treatment at a price that provides that ROI. Clinical trials in the US or Europe are insanely expensive and you cannot even budget them: Adverse reactions by "male patients over 45, born on a new moon Tue…

But for an insurance company, the ROI on curing someone’s hemophilia may be very very large. On the more consumer side of things, being able to fix some sort of obnoxious but perfectly survivable condition that genetic engineering may be able to solve (say lactose intolerant) may be something that you could sell to a lot of people.

From the POV of an insurance company, the patient might go elsewhere in a few years and they would only partially benefit from a cure.

Re: Haemophilia A trial results 'mind-blowing'

#106

Post by wahern »

DoreenMichele wrote: post #97
carbocation wrote: post #96

Earlier quoted context omitted.

I don't think there is a relationship between your personal experience and the OP's claim that diseases, broadly, are typically mediated by the gut microbiome.

So explain to me how 70% of the body's immune cells being in the gut is unrelated to how diseases are typically mediated. Pretty please.

The gut contains 70% of immune cells because your gut is actually the main point of contact between your body and the external environment. The surface area of your gut is somewhere from 20x to 100x that of your skin.

One could just as well argue that because the immune system is so well developed and robust in the gut that it's the last place to look for dysfunction. Or one could argue that a 70% share of immune cells is rather low considering the relative ratio of environmentally-exposed surface area.

We could say all kinds of things if we're free to make unsubstantiated conjectures. But we really can't say anything of substance without context and evidence. The human organism is ridiculously complex and consistently defies intuition.

Re: Haemophilia A trial results 'mind-blowing'

#107

Post by MBCook »

kgwgk wrote: post #105
MBCook wrote: post #102

Earlier quoted context omitted.

But for an insurance company, the ROI on curing someone’s hemophilia may be very very large. On the more consumer side of things, being able to fix some sort of obnoxious but perfectly survivable condition that genetic engineering may be able to solve (say lactose intolerant) may be something that you could sell to a lot of people.

From the POV of an insurance company, the patient might go elsewhere in a few years and they would only partially benefit from a cure.

True. Well, for young people.

For Medicare or certain people on Medicaid it might be worth it.

Re: Haemophilia A trial results 'mind-blowing'

#108

Post by selectodude »

mikecsh wrote: post #84
nycdatasci wrote: post #55

Earlier quoted context omitted.

The original comment was not suggesting that all genetic diseases and cancer (!) can be easily cured. Based on similar techniques, many single-gene disorders are effectively cured. Unfortunately, our disease-specific drug approval process does not scale and prevents us from realizing the benefits of these techniques and technologies. As a personal example, a close family member was recently diagnosed with shwachman-d…

> Based on similar techniques, many single-gene disorders are effectively cured. This is a bit of a leap. In principle (some of) the technology "is there" but there is a huge amount of complexity in the steps 1 through 5! > Yet doctors can't engage in this work without going through the lengthy drug trial process. I think it needs to be said that the "lengthy drug trial process" exists for extremely good reasons. Wer…

>thalidomide

Excuse my ignorance here, but has there been a single other drug that the FDA has stopped before it became an issue that a less insanely thorough process wouldn't have? It seems like the FDA was right about thalidomide and has been using that as justification ever since. At this point, clinical trials have become so onerous that the FDA can't even vet them and just trusts the drug companies to be above board.

Re: Haemophilia A trial results 'mind-blowing'

#109

Post by refurb »

mrfusion wrote: post #63

Could we do the same thing with sickle cell?

Yes, there is a company whose name escapes me working on it - Bluebird? You insert the correct hemoglobin gene and express it at a high enough level that you drive the percentage of sickle hemoglobin low enough that you no longer get the sickle cell crises.

Last I read they were having trouble getting durable expression.

Re: Haemophilia A trial results 'mind-blowing'

#110

Post by tialaramex »

aaavl2821 wrote: post #99
ImSkeptical wrote: post #88

Earlier quoted context omitted.

It's some kind of philosophical ethics problem that we can't experiment on humans even though there would be a net benefit. I feel like there are morally unintuitive solutions that may help - perhaps criminals of certain kinds, who have damaged society, could repay their debt, in part, by volunteering for trials we can be sure they understand. We might also leverage The suicidal by offering, after therapy, a way for…

I understand where you are coming from logically, although I am of the belief that this is not ethically acceptable. Ethics aside, jumping straight to human testing without assessing safety wouldnt really save that much in terms of cost and time to develop a drug, compared to developing better in vitro and animal models of disease safety studies are not the largest driver of cost and duration of drug development. fai…

IIRC There's already a special case where you can volunteer to try things if you're dying. If you have a rare cancer and doctors are like "Six months maybe less" and there's some crazy Hail Mary drug, which could work but isn't tested yet, you can volunteer to try it and see what happens. You can't pay (so it's for science, not a chance to get rich selling false hope), and you must be advised by doctors who have no financial interest, something like that. Judges were like, eh, you're dead anyway, what's the worst that could happen?

This trial was phase I/IIa which I believe means it's combining safety in humans with initial efficacy data. The thinking is, the real treatment is a single dose. If we give participants less than a full size dose we don't learn much from that. If we give them a real dose, we might as well see if it works.

So their endpoints were firstly how is the treatment tolerated, then secondly does it reduce the need to take clotting factors? Hence this good news story.

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