Scientists have been excited about the prospect of genetically modifying patients’ immune cells to make them resistant to disease since doctors effectively cured an HIV patient in 2008.
Timothy Brown, also known as the Berlin patient, had a bone-marrow transplant to treat his leukemia. Spotting their chance to treat both conditions, his doctors found a donor who carried the mutation that made their immune cells resistant to HIV. White blood cells are made in the bone marrow. Since the operation, Brown has had no detectable level of HIV in his body and no longer takes anti-HIV drugs.
Bone marrow transplants are risky operations and cannot be given to everyone with HIV. However, modifying patients’ immune cells might be the next best thing. One shortcoming of the latest therapy is that the patients still make normal white blood cells, which can and will be infected by the HIV virus.
Levine said one hope for the future was to genetically modify stem cells in the patient’s bone marrow so that they grow into immune cells. Those patients might then produce a steady flow of resistant immune cells, leaving HIV nowhere to hide.
The WHO estimated that in 2012, 35.3 million people globally were infected with HIV. About 2.3 million became infected that year, with more than 1.5 million dying from AIDS-related causes. About 100,000 people live with HIV in the UK, though it is estimated that one-fifth are undiagnosed.
The latest treatment was not without its problems. In the New England Journal of Medicine, the authors report a total of 130 mild or moderate side effects, 32 of which were linked to the modified cells rather than the infusion procedure. The most common reactions were fever, chills, headaches, muscle and joint pain. One patient was taken to the hospital’s emergency department after falling ill. The scientists note too that the patients’ body odor took on the smell of garlic, a consequence of them breaking down dimethyl sulfoxide, used to preserve the genetically modified cells.
The results of the trial were welcomed by other scientists. Angus Dalgleish, an expert in HIV at St George’s hospital in London, who was not involved in the study, said the cost of antiretroviral drugs over a patient’s lifetime and the side effects some patients face meant there was a real need for an alternative therapy.
“Anything that will prevent patients being on drugs the whole time, that allows you to manage the infection without those drugs, is a serious contender,” he said.
The research team now hopes to begin larger trials.
George Church, a geneticist at Harvard University, said that the Pennsylvania team’s therapy was “very important” because it showed that gene editing could be used to help large sections of the population. He and others are working on new forms of gene editing that could allow more precise genetic modification of human cells.