The National Institutes of Health has awarded a 5-year, $20-million grant to the Fred Hutchinson Cancer Research Center to test ” whether a person’s own stem cells can be engineered to deny HIV entry into the body’s blood cells.”
The possibility of a cure for HIV is more than a little mind-boggling after so many years where the best hope was simply to arrest the virus’s progression. In addition, the stem cell approach arose from a mysteriously Continental case that sounded like a co-production of Lifetime and Syfy.
Known as “the Berlin patient,” Timothy Ray Brown was both HIV-positive and dying of leukemia when his doctor suggested a radical approach: They would try transplanting bone marrow using cells from a donor with the CCR5 delta 32 mutation. That’s a very rare mutation that leaves immune cells resistant to HIV; they lack the receptor that HIV uses to infect new cells, leaving the virus stymied.
“People with two copies of the CCR5 delta32 gene (inherited from both parents) are virtually immune to HIV infection. This occurs in about 1% of Caucasian people,” writes Stanford’s Dr. Robin Kimmel. (Even mutants are not HIV-bulletproof, however, as there are HIV mutants that don’t use the missing receptor to infect new cells.)
Because of the specificity of the CCR5 mutation, found in Western European Caucasians, it seems likely to have been selected for, perhaps by an earlier virus. People with the mutation are otherwise healthy.
The Hutchinson Center team–researchers from Sangamo Biosciences of Richmond, CA; Beckman Research Institute at City of Hope in Duarte, CA; the University of Washington; and Seattle Children’s–plans to genetically modify patients’ own stem cells to shut off the HIV-hijack receptor, and then use their expertise in transplantation (which the Center uses to treat and cure blood cancers and some autoimmune diseases–boosting survival rates from nearly zero to 90 percent for certain types of leukemia) to permanently forestall HIV infection.
Both parts of this two-step formula are tricky. First, the researchers have to learn how to create the CCR5 delta 32 mutation, or something very like it. Then, they need to make sure that that change doesn’t create problems in transplantation.
A second “second part” of the overall HIV cure requires that they as well eliminate stores of “sleeper” HIV cells that accumulate in the body. The researchers will work on creating DNA-targeting proteins that go looking for pockets of HIV provirus–without attacking the infected cells globally. (These reservoirs of infected cells are why highly active antiretroviral therapy, or HAART, can’t be discontinued.)
This one-two punch, if successful, should eliminate the HIV virus entirely from a patient’s body. If all goes well, human clinical trials could begin in five years.
