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Haemophilia A trial results 'mind-blowing'

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Re: Haemophilia A trial results 'mind-blowing'

#81

Post by Brakenshire »

nycdatasci wrote: post #55
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…

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…

> 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 vs. drug-based cures or treatments. The system is set up for the latter, but is not comfortable with the former.

Re: Haemophilia A trial results 'mind-blowing'

#83

Post by jlg23 »

Brakenshire wrote: post #81
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…

> 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 Tuesday"? In worst case you restart the trial, excluding the problematic group to at least get the proof of safety and effectiveness for some part of the population so you can finally make some money...

Re: Haemophilia A trial results 'mind-blowing'

#84

Post by mikecsh »

nycdatasci wrote: post #55
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…

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. Were a treatment to be shown to be so incredibly effective during the trial process, based on pre-defined statistics monitored by an independent data safety monitoring committee, the trial would be stopped as it would be unethical not to provide all patients with the clear benefits. (recent example: https://www.ncbi.nlm.nih.gov/pubmed/29132880)

> So instead, they recommend much riskier treatment options including some that would complicate future gene-therapy attempts.

I believe it is unquestionable that doctors should be advocating treatment based on the best available evidence, and that the process for obtaining said evidence is a thorough and rigorous as possible, otherwise great harm can be done (classic example, thalidomide).

I would question the doctor that routinely recommended an experimental treatment which has not been shown to be efficacious over a "risky procedure" which has been shown to have $X efficacy.

Making patients aware of trials which may be of benefit to them is a valid and valuable part of medical practice, which is not always done very well. This is improving (in the UK at least) with greater numbers of research nurses and the use of databases such as https://www.ukctg.nihr.ac.uk.

Re: Haemophilia A trial results 'mind-blowing'

#86

Post by DoreenMichele »

carbocation wrote: post #18
will_brown wrote: post #13

Earlier quoted context omitted.

>Many diseases are as simple as your eyes being brown vs blue - you simply have or lack particular proteins. I think the other half of this is the microbiome. I have been speaking to physicians about leaky gut recently and a great analogy is the protein genes are like a piano and the microbiome is like the musician. As you suggest the genes/piano is sort of the hand you are dealt (you have the gene for certain diseas…

> the microbiome is what will typically unlock those diseases or not given the gene set If true, that would be a Nobel-worthy finding. I don't think this is true, but do you have a citation supporting this for the "typical" genetic disease?

I don't think that is far-fetched. The gut contains about 70% of the cells of your immune system.

I have a genetic disorder. Working on my gut health has gone a long way towards reversing my symptoms.

I don't talk about it as much as I used to because it was a constant shit show from people being completely dismissive, outright calling me crazy and asserting utterly illogical things in the name of their "scientific" bias, like "Your 13+ years of steady forward health progress in the face of your degenerative condition is merely wild coincidence and doesn't prove that you know anything at all. Stranger things have happened!"

Cuz, yeah.

People who see themselves as scientific and logical are very often not remotely objective. They just have college degrees or whatever to justify their ugly personal prejudices, and don't confuse them with the facts.

Re: Haemophilia A trial results 'mind-blowing'

#87

Post by DoreenMichele »

will_brown wrote: post #13
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…

>Many diseases are as simple as your eyes being brown vs blue - you simply have or lack particular proteins. I think the other half of this is the microbiome. I have been speaking to physicians about leaky gut recently and a great analogy is the protein genes are like a piano and the microbiome is like the musician. As you suggest the genes/piano is sort of the hand you are dealt (you have the gene for certain diseas…

As you suggest the genes/piano is sort of the hand you are dealt (you have the gene for certain disease or not), but the microbiome is what will typically unlock those diseases or not given the gene set.

The way I used to describe it was that your genes are like the blueprints for a house and what you eat is like local building materials. The blueprints may specify 2 bedrooms, one bathroom, but exactly how that will look will depend a lot on the vernacular architecture. Is it adobe brick because you live in the American Southwest? Is it made of blocks of ice because you are an Inuit? Etc.

So, different building materials have different strengths and weaknesses. This will significantly impact things like ceiling height and room size because what shapes the material supports will vary, depending on the material.

I'm sorry some people are reflexively downvoting. I hate it that so many people who imagine themselves to be scientific are so incredibly dismissive of stuff like this.

Re: Haemophilia A trial results 'mind-blowing'

#88

Post by ImSkeptical »

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…

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 them to live in comfort while contributing to humanity as experimental subjects.

I realize the mind recoils instinctively at these ideas, but it seems so frustrating and horrific that we have to delay life saving medical advanced due to insufficient experimental subjects.

Re: Haemophilia A trial results 'mind-blowing'

#89

Post by Nomentatus »

Q6T46nT668w6i3m wrote: post #24
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…

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…

True, and it's probably also worth noting that even "single gene" diseases can still be environmental illnesses; dependent on a modern condition or conditions that didn't occur a hundred thousand years ago or more; and nonexistent (despite the presence of that gene) back then.

Re: Haemophilia A trial results 'mind-blowing'

#90

Post by Nomentatus »

sswaner wrote: post #8

There is a pretty strong argument that Haemophilia is the disease that has had the biggest impact on the last 100 years. Russian heir to the throne Alexis Romanov inherited the disease and his suffering and lack of treatment options destabilized his family and contributed to leadership issues culminating in Russian defeat in WW1 and the Russian revolution and the rise of the Soviet Union. Agree? If not, what disease…

Possible, but... Russia being able to mobilize faster at the start of WWI than the Germans believed possible diverted enough additional troops East (busting their original plan) that the German invasion of France was too weak to succeed. There may be a better argument for Russia being stronger than could reasonably have been expected. Granted, French-subsidized railways and Austrian incompetence were very large factors, here.

The follow-on Kerensky government proved even less effective militarily, although it can be argued that the consequences of a century of mismanagement favoring the 1% wasn't easily reversed.

Malaria has defeated many an army and invasion; yellow fever, too. The fall of Rome has been blamed on a severe plague; particularly the fact that Rome was hit last, and therefore weak when it's neighbors were recovering and stronger.

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