MOLECULAR SYNOVECTOMY BY IN VIVO GENE TRANSFER: A PHASE I TRIAL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our group of physicians and scientists is interested in researching a new experimental method of decreasing the amount of joint destruction in patients with rheumatoid arthritis. The process of joint destruction is caused in part by the abnormal growth of cells that line the joint space. These cells grow into and destroy the cartilage and bone within the joint. These cells also are associated with the inflammation that is present within the joints of people with rheumatoid arthritis. Often, when these cells and inflamed tissues cannot be treated with medicine, the tissue can be removed using surgery. While this type of surgery does not cure the disease within a specific joint it may provide improvement for months or even years. Our procedure is designed to kill these abnormal cells within a single joint without the use of surgery through a combination of gene transfer as an experimental treatment and the intravenous administration of a drug ordinarily used to fight certain viral infections. By injecting a gene for a protein normally made by herpes viruses into the knee joint where it will be taken up by the abnormal cells that line the joint cavity, we hope to make those cells vulnerable to a drug called ganciclovir, which will be given intravenously. Previous studies have shown that removal of the synovial joint lining surgically, or injuring it through the use of chemicals or radiation therapy, often leads to long term improvement of the arthritis within that joint. We hope to accomplish the same thing in a much more selective fashion. The combination of the gene and the anti-viral drug should result only in the death of the synovial lining cells, which many investigators feel may lead to a long term remission of arthritis in the joint that has been treated with this method.