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Haemophilia A trial results 'mind-blowing'

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Re: Haemophilia A trial results 'mind-blowing'

#51

Post by dekhn »

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.

"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.

Re: Haemophilia A trial results 'mind-blowing'

#52

Post by aaavl2821 »

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?

"microbiome" therapies has been one of the hottest areas in biotech the last five or so years. some of the hype has died down, however. microbiome therapies work well in c. difficile infections and some other gut diseases. in this case, you give a patient a set of "good" microbes that fight the "bad" microbes (c. diff).

people are studying microbiome therapies for cancer, autoimmune disease, cns disease, etc, but its way too early to tell if any of it is real. there are many challenges: how do you ensure the microbes you administer stay in the body, colonize, and actually produce the molecules you want them to? how do you manage the risk that they interact with other microbe populations in ways that are impossible to predict accurately, but potentially very harmful? how do you manufacture these things in a consistent, high quality way? what is the regulatory path? how do you justify a huge risky r&d investment when you can't patent a microbe? not to mention the biology risk; the "microbiome thesis" sounds nice, but how confident are we that microbes can treat cancer, depression, parkinsons? right now, not very

Re: Haemophilia A trial results 'mind-blowing'

#53

Post by baldfat »

aaavl2821 wrote: post #41
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.

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/

Re: Haemophilia A trial results 'mind-blowing'

#54

Post by akuafo »

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…

My son also has hemophilia A and I'm fascinated by the possibility that he may someday join one of these trials.

The increase in the pipeline of gene therapies just in the past few months has been incredible.

Here are the ones I'm tracking: BioMarin valoctocogene roxaparvovec (BMN-270) Spark SPK-8011 Sangamo (Pfizer) SB-525 Bioverativ BIVV-001 Shire SHP-654 (BAX-888)

Re: Haemophilia A trial results 'mind-blowing'

#55

Post by nycdatasci »

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…

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-diamond syndrome (SDS). I have confirmed with multiple leading physicians (Dana Farber, Mayo Clinic, etc) that all of the tools necessary to cure her are presently available. At a high level, this would involve: 1. Extracting marrow. 2. Isolating blood-cell producing stem cells & amplifying in a dish. 3. Modifying using a product like [A] 4. Validating/re-sequencing to confirm transduction. 5. Re-insert modified cells into patient.

Yet doctors can't engage in this work without going through the lengthy drug trial process. So instead, they recommend much riskier treatment options including some that would complicate future gene-therapy attempts.

[A] - https://crispr.sigmainformatics.com/templates/CRISPR%20Custo...

Re: Haemophilia A trial results 'mind-blowing'

#56

Post by olegkikin »

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...

Re: Haemophilia A trial results 'mind-blowing'

#57

Post by aaavl2821 »

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/

yeah artificial pancreas seems to be the most promising near-term development. the field has suffered from a lack of funding for translational research as VCs have been focused on other diseases, but hopefully that changes. semma (a startup turning stem cells into beta cells) raised $114M last week

Re: Haemophilia A trial results 'mind-blowing'

#58

Post by dekhn »

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.

well, stem cells are special in that they form tree replication structures to avoid problems like the Hayflick limit, so if the ones high up in the tree got repaired, you should have new stem cells born that inherit the fix for decades. At least, that's my understanding of the theory; that's no guarantee it works that way in reality.
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