Gene therapy for HIV shows promise

日期:2019-03-01 11:10:05 作者:百里筷踅 阅读:

By Andy Coghlan The largest clinical trial yet mounted to test a gene therapy against HIV has yielded modest benefits for patients and proved safe. “To our knowledge, our study was the first randomised, controlled study performed with gene therapy in HIV,” says the head of the trial, Ronald Mitsuyasu of the University of California, Los Angeles. Patients temporarily stopped their usual regime of anti-retroviral treatment (ART) to see whether the gene therapy would work as effectively. Half the 74 patients received the treatment, and half a placebo. Although the gene therapy didn’t work as well as ART, virus concentrations in blood were on average about a third lower in recipients of the treatment than in controls who received a placebo. Also, recipients had higher numbers of CD4+ white blood cells, the type that is attacked by the virus. “It provides proof of concept and early indications are that, with more refinement, this approach may be a viable one for controlling HIV directly in people without the need for continuous HIV medication,” Mitsuyasu says. “From a scientific standpoint, it represents a new and potentially important and long-lasting way of controlling diseases,” he adds. Mitsuyasu and his colleagues took blood samples from patients and isolated CD34+ stem cells, which can mature into many types of white blood cell, including the CD4+ cells attacked by HIV. Then, they used a harmless virus to load the stem cells with an extra gene that makes a ribozyme – a pair of molecular “scissors” targeted at the virus. Earlier experiments in cell cultures showed that if such cells are invaded by HIV, the ribozyme is produced and cuts up tat, a gene essential for the virus to replicate itself. The hope was that when altered cells were returned to the patient, they would grow into white blood cells that survive attack by the virus and prevent it from multiplying and infecting other cells. Effectively, the immune system would become resistant to HIV, as the altered cells would be the only ones surviving. The results demonstrated that the patients with more altered cells had correspondingly lower levels of virus and marginally more CD4+ cells. However, the altered cells did wane in number towards the end of the 100-day “break” from ART treatment, the opposite of what was hoped. “Work is ongoing to develop better and more effective ways of performing gene insertion and allowing these genes to be better expressed in patients for longer periods of time,” said Mitsuyasu. The altered stem cells might have worked better if existing stem cells from the bone marrow had all been destroyed beforehand, as in earlier mouse experiments, allowing the altered cells to take over in the empty bone marrow. This was too dangerous to be ethically justifiable in people, though, as the patients would have been minus their entire immune system in an experiment which may have failed to replace them. Journal reference: Nature Medicine (DOI: 10.1038/nm.1932) More on these topics: