Haemophilia A trial results 'mind-blowing'
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Re: Haemophilia A trial results 'mind-blowing'
#2Awesome 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?
Re: Haemophilia A trial results 'mind-blowing'
#3This could be huge. Hemophilia is one of the most expensive diseases to treat out there. I worked with a client that provides software to hemophilia clinics, and while modern factor drugs have made it so that sufferers can live relatively normal lives, it's still a very challenging disease with many long term complications.
Re: Haemophilia A trial results 'mind-blowing'
#4Awesome 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?
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Re: Haemophilia A trial results 'mind-blowing'
#5What 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 the body prior to gene therapy, the advances in viral vectors may be just as empowering as the therapy itself. Imagine, in all the irony, getting “vaccines” as a child via viral vectors against common causes of poor health local to your birthplace. An enjoyable quote from a Paul Berg which holds true, of course - “Fears of creating new kinds of plagues or of altering human evolution or of irreversibly altering the environment were only some of the concerns that were rampant”.
Re: Haemophilia A trial results 'mind-blowing'
#6Awesome 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 observed in similar clinical trials of vector gene transfer,13,19,29 vector DNA was detected in various biologic fluids obtained from all the participants (see the Vector Shedding–Discussion section in the Supplementary Appendix). The possibility of vector integration was not assessed. The protocol was not designed to measure whether AAV5 infection was present in family members or close contacts, and ethics approval was not sought to pursue this question. The two viral genes within AAV5 have been replaced by factor VIII, and AAV5 requires another virus such as an adenovirus for a productive infection."""
This is a surprising finding because normally AAV5 leads to an immune response in this kind of treatment, although symptoms are mild and the virus in general is not considered pathogenic.
The mechanism of integration is described in detail in the wikipedia page. https://en.wikipedia.org/wiki/Adeno-associated_virus
I think if this worked as intended, no additional treatment is required.
Re: Haemophilia A trial results 'mind-blowing'
#7What 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…
Journal article is at http://www.nejm.org/doi/full/10.1056/NEJMoa1708483#t=article
They used AAV (actually, take a look at the article, they give a nice and clear explanation of what modifications they had to make).
Re: Haemophilia A trial results 'mind-blowing'
#8There 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 led to a greater string of consequences? Malaria, Spanish Influenza, polio, AIDS?
Re: Haemophilia A trial results 'mind-blowing'
#9There 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…
The plague in Europe. And in North America, smallpox, which decimated (and more) indigenous peoples.
Re: Haemophilia A trial results 'mind-blowing'
#10There 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…
The plague in Europe. And in North America, smallpox, which decimated (and more) indigenous peoples.
Neither of which occurred in the last 100 years.