Gene Therapy Safe for Arthritis

A recent report described results of a human clinical trial that tested the efficacy and safety of gene therapy for the treatment of arthritis.

Investigators at the University of Pittsburgh School of Medicine (PA, USA) performed the study from 1996 to 1999 on a group of nine women from 49 to 73 years of age suffering from advanced rheumatoid arthritis. Each of the patients was scheduled to receive artificial joints. Before surgery they participated in the gene therapy study. As other researchers had found evidence that the viral vector used in the study could cause leukemia, follow-up was continued for five years.

Cultures of each patient's synovial fibroblasts were established and divided into two. One was transduced with a retrovirus carrying IL-1Ra cDNA while the other provided untransduced, control cells. The transformed cells were injected into two metacarpophalangeal (MCP) joints, and non-transformed cells were injected into two other MCP joints. One week later, the injected joints were removed and examined for evidence of successful gene transfer and expression by using RT-PCR (reverse transcription-polymerase chain reaction), production of IL-1Ra, in situ hybridization, and immunohistochemistry.

Results published in the June 6, 2005, online edition of the [U. S.] National Proceedings of the National Academy of Sciences revealed that the joints receiving the transduced cells gave positive RT-PCR signals. The control joints were negative. Of prime importance was the finding that after five years follow-up there was no evidence that the genetically modified cells had caused any adverse events in any of the nine patients.

"Given that gene therapy was so new and we were dealing with an otherwise healthy patient population, the ex vivo protocol was the most appropriate approach to take at the time,” said contributing author Dr. Paul Robbins, professor of molecular genetics, biochemistry, and orthopedic surgery at the University of Pittsburgh School of Medicine.