8 ms·

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

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?

deleted 9y ago
[deleted]
dekhn 9y ago
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 The two viral genes within AAV5 have been replaced by factor VIII, and AAV5 requires another virus such as an adenovirus for a productive infection."""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 https://en.wikipedia.org/wiki/Adeno-associated_virus I think if this worked as intended, no additional treatment is required.
- seren 9y ago
  > 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.
  - Chriky 9y ago
    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 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.
    - seren 9y ago
      Thanks for clarifying my misconceptions !
    - jessriedel 9y ago
      Thanks for sharing! Can I ask what considerations went into your decision? Will you be pursuing this now that there is more evidence that it's effective?
      - Chriky 9y ago
        I mean, obviously I regret it now, but at the time I had no idea it would work. I'm sure the next trial will be extremely oversubscribed! I think my trial was actually for a low dose version to test safety of the vector and it didn't have any clinical effects. Its quite incredible though, there's only a few thousand people in the UK with haemophilia - this trial just cured like 0.5% of them
        toomuchtodo 9y ago
        Would you mind keeping us updated if you pursue the next clinical trial? Happy to kick in Patreon money for your time. (Not a wierdo, just deeply interested in Curing All The Things).
        9y ago

deleted 9y ago

[deleted]

dekhn 9y ago

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 https://en.wikipedia.org/wiki/Adeno-associated_virus I think if this worked as intended, no additional treatment is required.

seren 9y ago
> 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.
- Chriky 9y ago
  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 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.
  - seren 9y ago
    Thanks for clarifying my misconceptions !
  - jessriedel 9y ago
    Thanks for sharing! Can I ask what considerations went into your decision? Will you be pursuing this now that there is more evidence that it's effective?
    - Chriky 9y ago
      I mean, obviously I regret it now, but at the time I had no idea it would work. I'm sure the next trial will be extremely oversubscribed! I think my trial was actually for a low dose version to test safety of the vector and it didn't have any clinical effects. Its quite incredible though, there's only a few thousand people in the UK with haemophilia - this trial just cured like 0.5% of them
      - toomuchtodo 9y ago
        Would you mind keeping us updated if you pursue the next clinical trial? Happy to kick in Patreon money for your time. (Not a wierdo, just deeply interested in Curing All The Things).
      - 9y ago