Gene therapy has been another promising area of arthritis research, but some wonder if it has now taken a back seat to the biologic drugs. Gene therapy is quite exciting when you consider the possibilities, but is in its infancy in terms of practical application.

Genes, estimated to number in the tens of thousands, play a significant role in the making of proteins. It is possible to identify genes, isolate the genes from cells, and copy them. Put into the cells of living organisms, the genes function the way they were intended.

What was just described is like a four-stage process: identify, isolate, copy, transfer. A vector is needed to carry the genes into the target cells. Complicated for sure, but remember the goal is to be able to transfer genes to humans so the proteins from the genes will treat or cure diseases.

Pittsburgh Trials

A sixty-eight-year-old woman, who was already scheduled to have surgery for knuckle replacements, agreed in April 1996 to allow orthopedic surgeons to remove the synovial membrane of one of her thumb joints, which they transferred to a sterile growth media in the laboratory. The cells reproduced, and some were genetically modified to carry a gene that blocks inflammation. In July, the surgeon injected two of the woman's knuckle joints with genetically modified cells and two untreated cells. About a week later, the woman had the intended knuckle replacement surgery. Tissue and fluid was kept to see if having the genetically modified cells was beneficial.

As described, this was the first groundbreaking gene therapy trial for rheumatoid arthritis. Afterward, over a period of a few years, eight other women underwent a similar procedure. No adverse effects were found, and that was the goal of the study — to assess safety.

German Trials

Around the same time as the Pittsburgh trials, researchers in Germany used an approach similar to the Pittsburgh researchers, but inserted their genetically modified cells a month, rather than a week, before surgery. Two people participated in the German trial in 2000, and it was found again that no adverse effects occurred and the injected cells functioned properly.

Michigan Trial

In 1999, a third rheumatoid arthritis gene therapy trial took place at the University of Michigan Medical Center. In this trial, a gene taken from a virus was used. After injecting the gene into living tissue, the gene enters some cells, causing them to make TK, an enzyme. TK is normally not present in human cells. The study participant then took gancyclovir, a drug not harmful to human cells. However, in cells that produced TK, gancyclovir is converted into something toxic to TK-producing cells. The goal of this approach would be to control thickening of the synovium.