Naked Science Forum
Life Sciences => Cells, Microbes & Viruses => Topic started by: thedoc on 13/03/2014 10:42:27
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Gene therapy can be used to modify the immune cells of patients with HIV, to make them much harder for the virus destroy...
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This treatment was also discussed on TWiV 278 http://www.twiv.tv/
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This sounds very similar to the Timothy Ray Brown (Berlin Patient) who required a bone marrow transplant for leukemia.
The doctors located a donor match who was CCR5 negative. Now several years post-transplant, he has been considered "cured" of both Aids and Leukemia.
So, the gene therapy has to be a subtractive gene therapy, essentially removing the CCR5 gene, or making it non functional.
I suppose the question is how long the T cells live, and how new ones are formed. If the body continues to make T-cells that are capable of being infected, then the infusion of a small number of disease free cells may help prevent symptoms, but may not actually cure the disease.
If a person had both CCR5 positive and negative cells in their body, would there be a risk of developing a mutation that ignores this receptor, and then spreading it into the general population?
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the question is how long the T cells live, and how new ones are formed
Blood cells are formed from bone marrow - the excess of white blood cells in leukemia comes from mutated cells in the bone marrow.
Before doing a bone marrow transplant, the existing bone marrow is killed (eg with radiation), and then the donor's bone marrow is injected.
After that, the patient's T cells will have the same genetic expression as the donor's DNA (which resists HIV), not the recipient's DNA (which is susceptible to HIV).
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Yes, in a marrow transplant, one ablates the original cells and introduces all new cells. However, a marrow transplant is a brutal, dangerous procedure.
I think the idea in this experiment is to modify people's T-Cells ex-vivo to not express the CCR5 marker, then reintroduce those cells, without doing anything to one's existing T Cells, or the marrow where they are generated.
RBCs, of course, have a short lifespan, but I believe the WBCs have a much longer lifespan, perhaps years or decades.
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This treatment just treats a population of T4 cells not the cells in the bone marrow, I understand that T cells, when stimulated by antigen can divide and increase. New T4 cells will still me made in the bone marrow and these could still be infected by HIV.
I presume that this treatment would need to be repeated at intervals, or that bone marrow be treated, but that would be a much more difficult and risky procedure.
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The difference between the study discussed above and the patient in Berlin "cured" of HIV is that the Berlin patient underwent allogeneic (from another individual) bone marrow transplantion necessitated by a diagnosis of lymphoma. In his case all of his CD4 cells post-transplant were derived from the new donor marrow stem cells; as these were CCR5-delta-32, they were resistant to HIV infection.
In the present study, patients are receiving their own cells back in a manipulated state with the CCR5-delta-32 gene excised. The result is mixed clones of CD4 cells that lack CCR5, making them also HIV resistant. These cells co-exist alongside the native (unmodified) cells. As the study authors speculate, this may be all that is required for long term good health.
Chris