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Haemophilia A trial results 'mind-blowing'

bbc.com

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Re: Haemophilia A trial results 'mind-blowing'

#11

Post by nervousvarun »

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…

Interesting question. Can the eradication/treatment of a disease be taken into account? Would think the wide-scale availability of vaccines for Polio/Small Pox/other various viruses etc coupled with antibiotic treatments for bacterial infections had an enormous impact on the last 100 years.

Re: Haemophilia A trial results 'mind-blowing'

#12

Post by seren »

dekhn wrote: post #6
testfoobar wrote: post #2

Awesome outcome. But the article is yada-yadaing over the good stuff. How are the new genes integrated into the patient's body? Why isn't the virus attacked by the immune system? Instead of regular factor shots, do they need regular viral-gene shots?

The virus is recognized, but not attacked: """After infusion, antibodies to AAV5 were detected in all the tested participants, but no T-cell–mediated immune responses to AAV5 capsid proteins were detected, and neutralizing antibodies to factor VIII did not develop in any participants. The absence of factor VIII inhibitors during more than 1 year of follow-up underscores the safety of AAV5-hFVIII-SQ. As has been obser…

> 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.

Re: Haemophilia A trial results 'mind-blowing'

#13

Post by will_brown »

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 disease or not), but the microbiome is what will typically unlock those diseases or not given the gene set. Another way of explaining this is that humans have about 20,000 genes, the most genes in any animal are about 35,000, and wheat has 164,000-334,000 genes. Obviously we are much more complex with the potential to carry many more diseases which physicians explained to m through humans having a microbiome.

Re: Haemophilia A trial results 'mind-blowing'

#14

Post by mistermann »

TylerE wrote: post #10
mirimir wrote: post #9

Earlier quoted context omitted.

The plague in Europe. And in North America, smallpox, which decimated (and more) indigenous peoples.

Neither of which occurred in the last 100 years.

I couldn't resist.

https://twitter.com/codinghorror/status/895774914820546560

Re: Haemophilia A trial results 'mind-blowing'

#15

Post by mirimir »

TylerE wrote: post #10
mirimir wrote: post #9

Earlier quoted context omitted.

The plague in Europe. And in North America, smallpox, which decimated (and more) indigenous peoples.

Neither of which occurred in the last 100 years.

OK, fair enough. Let's see ... 100 years. How about nationalism?

Re: Haemophilia A trial results 'mind-blowing'

#16

Post by liveoneggs »

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…

syphilis increased the crazy of many many important people until antibiotics came into common use

Re: Haemophilia A trial results 'mind-blowing'

#17

Post by dghughes »

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…

That's like a James Burke Connections episode.

Re: Haemophilia A trial results 'mind-blowing'

#18

Post by carbocation »

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…

> 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?

Re: Haemophilia A trial results 'mind-blowing'

#19

Post by Chriky »

seren wrote: post #12
dekhn wrote: post #6

Earlier quoted context omitted.

The virus is recognized, but not attacked: """After infusion, antibodies to AAV5 were detected in all the tested participants, but no T-cell–mediated immune responses to AAV5 capsid proteins were detected, and neutralizing antibodies to factor VIII did not develop in any participants. The absence of factor VIII inhibitors during more than 1 year of follow-up underscores the safety of AAV5-hFVIII-SQ. As has been obser…

> 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 provide the functional genes, it is expected that you may not require treatment for Haemophilia A, as often or at all."

I don't really want to upload the whole Participant Information Sheet because it contains some of the doctor's personal details.

Re: Haemophilia A trial results 'mind-blowing'

#20

Post by jessriedel »

seren wrote: post #12
dekhn wrote: post #6

Earlier quoted context omitted.

The virus is recognized, but not attacked: """After infusion, antibodies to AAV5 were detected in all the tested participants, but no T-cell–mediated immune responses to AAV5 capsid proteins were detected, and neutralizing antibodies to factor VIII did not develop in any participants. The absence of factor VIII inhibitors during more than 1 year of follow-up underscores the safety of AAV5-hFVIII-SQ. As has been obser…

> 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.

Surprising to me:

> As for the liver, the human body's detoxifier, its cells' lives are quite short - an adult human liver cell has a turnover time of 300 to 500 days.

https://www.timeshighereducation.com/news/life-span-of-human...

So I think it must be targeting the stem cells or this wouldn't last more than a year or two? EDIT: See Chriky's comment.

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