5 ms·

>The remaining bone marrow cells are killed by chemotherapy, then replaced by the edited cells. Interesting that they need to kill the remaining bone marrow ce

by 34679 6y ago

>The remaining bone marrow cells are killed by chemotherapy, then replaced by the edited cells. Interesting that they need to kill the remaining bone marrow cells. I wonder what happens when they skip that step. Do the modified cells still reproduce, resulting in a partially effective treatment? Are they targeted by the immune system and eliminated? Are they just out-reproduced by the normal cells and fade into irrelevance?

deleted 6y ago
[deleted]
simcop2387 6y ago
More than likely I'd imagine it's the last option. They can only produce so many of the edited cells. The body is going to have orders of magnitude more of the original ones present before the treatment that I think they'd just overwhelm the new ones. If you remove the original ones the new ones have a place to thrive and eventually get to normal levels
koheripbal 6y ago
That depends on the nature of the genetic disease. If the original gene produces a protein that actively causes an issue in the body, versus if the gene produces a broken protein that simply fails to do its job. In the first case, a partial replacement means that the original active protein continues to cause the disease. In the second case, a partial replacement means that the repaired protein begins expressing itself. In either case, there may or may not be a linear correlation between the percentage of fixed proteins and the severity of the disease, and that relationship probably isn't well understood in most disease cases, but a partial replacement is likely much more beneficial in the second case, rather than the first. That is why these initial test are done on chemo patients, so that we can isolate testing of the method of treatment without needed to know what amount of the original tissue needs to be replaced. There is still a long complicated road ahead. Not a lot of organs get fully replaced in other procedures.
refurb 6y ago
If you don't kill off the existing bone marrow, you end up with a couple problems: 1. You only give the patient a small number of edited cells. You want those cells to multiply and replace the existing cells. If you don't remove the existing cells, the edited cells aren't going to reproduce very fast because the body has a feedback loop and is saying "we have enough bone marrow cells now, so no need to make more". 2. Host versus graft disease. The old immune system will attack the new immune system cells.
- enchiridion 6y ago
  Do these patients have to be revaccinated?
  - refurb 6y ago
    I’m not a doctor, but I would say yes, you’d lose any acquired immunity since you kill off all the memory b-cells that store that information. But you’d also gain the donor’s immunity, and if they’ve been vaccinated, the recipient would have that immunity as well.
    - rnet85 6y ago
      That is not correct. Trained B cells are predominantly stored in lymph nodes. You also don’t gain host immunity by marrow transfer.
      - enchiridion 6y ago
        So B cells are what responsible for learned immunity?
BurningFrog 6y ago
You can think of this as "turning the immune system off and on again", IT Crowd style. I've heard it discussed as a possible way to treat autoimmune diseases like MS.

by 34679 6y ago

deleted 6y ago

[deleted]

simcop2387 6y ago

More than likely I'd imagine it's the last option. They can only produce so many of the edited cells. The body is going to have orders of magnitude more of the original ones present before the treatment that I think they'd just overwhelm the new ones. If you remove the original ones the new ones have a place to thrive and eventually get to normal levels

koheripbal 6y ago

That depends on the nature of the genetic disease. If the original gene produces a protein that actively causes an issue in the body, versus if the gene produces a broken protein that simply fails to do its job. In the first case, a partial replacement means that the original active protein continues to cause the disease. In the second case, a partial replacement means that the repaired protein begins expressing itself. In either case, there may or may not be a linear correlation between the percentage of fixed proteins and the severity of the disease, and that relationship probably isn't well understood in most disease cases, but a partial replacement is likely much more beneficial in the second case, rather than the first. That is why these initial test are done on chemo patients, so that we can isolate testing of the method of treatment without needed to know what amount of the original tissue needs to be replaced. There is still a long complicated road ahead. Not a lot of organs get fully replaced in other procedures.

refurb 6y ago

If you don't kill off the existing bone marrow, you end up with a couple problems: 1. You only give the patient a small number of edited cells. You want those cells to multiply and replace the existing cells. If you don't remove the existing cells, the edited cells aren't going to reproduce very fast because the body has a feedback loop and is saying "we have enough bone marrow cells now, so no need to make more". 2. Host versus graft disease. The old immune system will attack the new immune system cells.

enchiridion 6y ago
Do these patients have to be revaccinated?
- refurb 6y ago
  I’m not a doctor, but I would say yes, you’d lose any acquired immunity since you kill off all the memory b-cells that store that information. But you’d also gain the donor’s immunity, and if they’ve been vaccinated, the recipient would have that immunity as well.
  - rnet85 6y ago
    That is not correct. Trained B cells are predominantly stored in lymph nodes. You also don’t gain host immunity by marrow transfer.
    - enchiridion 6y ago
      So B cells are what responsible for learned immunity?

BurningFrog 6y ago

You can think of this as "turning the immune system off and on again", IT Crowd style. I've heard it discussed as a possible way to treat autoimmune diseases like MS.