Gene therapy could be a safe and effective way of treating rheumatoid arthritis, say US researchers. In a small study, published early online in the Proceedings of the National Academy of Sciences, nine women received injections of genetically modified cells. The research, carried out at the University of Pittsburgh School of Medicine, suggests that the novel treatment could eventually be used to treat inflammation and pain caused by both rheumatoid and osteoarthritis.
The scientists carried out the preliminary trial between 1996 and 1999. The women taking part were aged between 49 and 73 years old, and had been living with rheumatoid arthritis for 10-26 years. All were due to receive joint replacement surgery involving four knuckles on one hand, and one additional joint. Prior to their operations, the scientists removed fluid from the additional joint, and grew the cells it contained in the laboratory for several weeks. They treated half the cells with a gene called IL-1 Ra - which makes a protein thought to block inflammation - and left the rest untreated. The women then received injections of the modified cells into two of their knuckles, and injections of untreated cells in the other two.
The team removed the four treated knuckles, which were then replaced with artificial joints as originally planned. The joints treated with the modified cells showed high levels of IL-1 Ra, showing that the gene therapy procedure had worked. The treated cells also had lower levels of chemicals known to trigger inflammation than the untreated cells. The researchers followed up the participants for five years, and found no evidence of any side effects of the treatment. The team used the same modified virus (vector) to deliver the therapeutic gene as used in a French gene therapy trial for an inherited immune disease called X-SCID (X-linked severe combined immunodeficiency), in which three patients developed leukaemia. 'Once we learned of the adverse events in the X-SCID trial, we decided it was best to extend follow-up of our patients to five years so that there'd be little question about long-term safety', said lead author Christopher Evans.
The researchers say that although their approach of removing and reinjecting the treated cells proved safe, it was also time-consuming, tedious and expensive. In future trials for both rheumatoid and osteoarthritis, they hope to use a different vector - an adeno-associated virus - to deliver the gene directly to the affected tissue. US bioethicist Arthur Caplan praised the study, particularly the decision to remove the modified cells shortly after they had been injected into the patients. 'It's slow, it's minimally invasive but still allows you to learn without jeopardising the health of the patient', he said. Caplan said that the approach of injecting an area that is due to be removed surgically could be used for testing other gene therapy treatments, and possibly, in the future, new stem-cell treatments.