reply to post by OGOldGreg
I had the privilege of meeting Timothy Ray Brown, the patient cured of AIDS. His story is indeed fascinating, scientifically, but his experience was
near torture. Here's just one interview with him:
www.youtube.com...
You'll notice his speech and cognition are impaired. That happened after the second bone marrow transplant. When his GVHD (graft vs host disease,
which we count on - the donor's healthy bone marrow cells will become normal, healthy immune cells and naturally seek out and kill leukemic cells
along with pretty much all of the host's immune cells) began attacking, he experienced a severely high fever, which left him with permanent brain
damage. He has neurologists working with him for free to help "repair" his cognitive problems.
The science behind the "cure" is quite simple. Remember I said way back in my earlier posts that HIV preferentially infects CD4 cells, well that's
somewhat simplified. There are actually two main types of HIV. Both prefer CD4 to be on the surface of the cell it infects as all forms of HIV bind
to CD4. Then one form of HIV (we call it R5-tropic) likes to also bind to the CCR5 receptor while another form (we call it X4-tropic) likes to also
bind to the CXCR4 receptor. Both CCR5 and CXCR4 are on the surface of immune cells and each receptor serves a different function in helping T cells
or macrophages know where they should be in the body and what exactly their role should. So, infecting cells that need CCR5 or CXCR4 to do their
jobs, impairs the immune system similarly to infecting CD4 cells.
But what's really interesting is there is a small population that is more enriched in Germany that have a mutation in their CCR5 gene so that the
protein/receptor is never expressed on the cell's surface! This mutation in the human population is thought to have come about when smallpox (which
also uses CCR5 to enter into cells) ravished Europe.
So now realize that there are a group of people (albeit small) who are less susceptible to HIV, at least one form of HIV. Would it be possible to
transfer the immune system from these people to HIV infected people, making the recipient less susceptible to HIV? Curing them? What an amazing
experiment that would be. But honestly, the process of a bone marrow transplant is really, really, really hard on the recipient. Sometimes people
even die from the transplant. So under what circumstances should we be willing to try this experiment? Especially since we are talking about
experimenting on humans, not on mice or lab rats.
Well, leukemia is often treated with bone marrow transplants. So when the doctor's working with Timothy Ray Brown realized that he had leukemia and
HIV and he happened to living in Germany, the place with the largest amount of CCR5 defective people in the world, they decided this was the man to
test their theory on. At first, after they told him of the risks and side effects, he said no. They asked him again, are you sure?! He said no.
So, they began traditional chemotherapy. But after a couple months, he did not "tolerate" the chemo - in other words, it nearly killed him and they
had to stop. He went off to Italy, to come to peace with the fact that he was going to die.
But the doctors would not give up and at great cost, they scanned all the donors in their database for one that was both an HLA match (for the bone
marrow part and curing leukemia) and was CCR5 defective. They found not one, but three! They implored Timothy Ray Brown again, please, please, let
us save you! He finally relented. The first bone marrow transplant seemed to treat the disease they were most concerned about since it was leukemia
killing him, not HIV. In fact, Timothy Ray Brown had been on HAART therapy and his viral loads were nearly undetectable. However, they suspended his
HAART treatment on the day of his first surgery and unlike most people, his viral loads never rebounded. Sadly, his leukemia did. And he needed a
second bone marrow transplant. This one cured his leukemia, but after the fight of his life, left him with the painful side effects of cognitive
impairment.
So, should this "cure" be available as a standard treatment for HIV? Sadly, less than 0.1% of the American population have this mutation, so
finding CCR5 defective donors is going to be a challenge. How about if we engineer the patient's own blood progenitor's cells (which essentially
come from the bone marrow) to be CCR5 defective? That is EXACTLY what we and others are doing!
www.sciencedaily.com...
www.aidsmeds.com...
clinicaltrials.gov...