Study Shows Rheumatoid Arthritis Responding To Gene Therapy
A study that delivers the first clinical evidence that gene therapy can reduce the symptoms of patients with rheumatoid arthritis appeared in the February issue of Human Gene Therapy. The authors of the study, which was carried out in 1997 and 1998 under the direction of Dr. Peter Wehling, Düsseldorf, Germany, describe the findings of a study involving two patients with severe rheumatoid arthritis.
In gene therapy, genes inside the cells are modified so as to either repair a genetic defect or to trigger the cells to produce a protein that stops the disease. The first clinical studies of such techniques began in 1990 for the treatment of rare genetic defects of the immune system. The gene transfer technique used in the present study was approved by the Ethics Committee of the Düsseldorf University Hospital.
Rheumatoid arthritis is a classic auto-immune disorder in which the body’s immune system turns against itself, resulting in swelling and inflammation of the joints. The disease causes permanent destruction of joint tissue, especially cartilage, and remains incurable. It is estimated that 5-10 million patients of the EU suffer from rheumatoid arthritis. “Rheumatoid arthritis is an extremely painful condition that can affect multiple joints of the body. It is an ideal indication for this technique because the joint forms a closed space. The genetically modified cells can simply be injected into the joint because they will stay in place”, notes Dr. Rüdiger Krauspe, director of the Orthopaedics Clinic at Düsseldorf University Hospital.
Lead investigator Peter Wehling explains the technique: “We injected genetically modified cells taken from the patient’s own body into the diseased joint. This stimulated the production of the human interleukin-1 receptor antagonist, which stops the breakdown of cartilage by blocking the interleukin-1 protein that is responsible for the inflammatory processes.“ “Essentially the gene becomes its own little factory, continuously working to alleviate pain in the joint “, says Christopher H. Evans of the Center for Molecular Orthopaedics, Harvard Medical School, Boston, one of the co‑authors of the study.
“Basically we were able to show that gene therapy is feasible and safe for arthritic disorders”, said co-author Dr. Julio Reinecke, molecular biologist with Orthogen, a Düsseldorf biotechnology company.
The study involved two female patients, both under the age of 75, with a diagnosis of advanced rheumatoid arthritis. (Due to complications related to an unrelated trial for a different immunodficiency disorder, only two of the six subjects originally approved to take part in the trial could be included.) Four weeks after receiving the injections, both patients reported reduced pain and swelling. In one of the subjects the effects were dramatic. The treated joint remained free of pain even when the patient experienced further flares of her symptoms in other, untreated joints. Laboratory testing of tissue from the treated joint showed lesser quantities of the interleukin-1 proteins, thus confirming that the reduced pain and swelling were results of the gene therapy.
The study shows that gene therapy produces clinical results and symptomatic relief in the treatment of rheumatoid arthritis, and that the method can be considered safe, at least over the period observed thus far. Further studies are needed to confirm this promising approach. The study was funded in part by grants from the Land of North-Rhine Westphalia and Orthogen AG.
The study was conducted jointly by the Düsseldorf University Hospital Orthopaedics Clinics, Orthogen Düsseldorf, and the University of Pittsburgh School of Medicine, along with Steven Ghivizzani of the University of Florida College of Medicine und Christopher H. Evans of the Center for Molecular Orthopaedics, Harvard Medical School, Boston.