Gene therapy for arthritis and other non-terminal, debilitating conditions and diseases is both feasible and safe, report researchers who conducted the world’s first such test on the approach in patients with advanced rheumatoid arthritis. The results, published in this week’s online edition of the Proceedings of the National Academy of Sciences (PNAS), indicate that introducing a new gene has the potential to block the destructive inflammation process that takes place within arthritic joints. At a time when setbacks have cast doubt on the future of gene therapy, the results also provide assurance that it can be performed without causing undue harm to patients. The clinical trial, which was conducted at the University of Pittsburgh School of Medicine between 1996 and 1999, involved nine women who had genetically modified cells injected into their arthritic knuckles and marked the first time a gene was introduced into a human joint. The researchers say their results showing that successful gene transfer can target joint inflammation open the door to the development of improved gene-based therapies for both rheumatoid and the more common osteoarthritis, which together affect about 66 million people in the United States. While the Pitt study used the same vector - an inactivated virus that shuttles a gene into cells - as a more recent French trial for X-linked severe combined immunodeficiency (X-SCID) in which three children later developed leukemia, the researchers point out that this is the only similarity between the two trials. The studies were concerned with different genes and with different targets, and in the arthritis trial, the transduced cells were removed after one week during routine joint replacement surgery. Nonetheless, with safety a key concern, the authors report no clinical side effects up to five years after the procedure and no evidence that the vector, a replication-defective retrovirus called Maloney Murine Leukemia Virus, has since become capable of replication in their patients.
