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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们的医生和科学家小组有兴趣研究一种新的实验方法来减少类风湿关节炎患者的关节破坏量。关节破坏的过程部分是由排列在关节间隙的细胞的异常生长引起的。这些细胞生长并破坏关节内的软骨和骨头。这些细胞也与类风湿性关节炎患者关节内的炎症有关。通常，当这些细胞和发炎组织不能用药物治疗时，可以通过手术切除这些组织。虽然这种类型的手术不能治愈特定关节内的疾病，但它可能在数月甚至数年内提供改善。我们的程序旨在通过结合基因转移作为实验性治疗和静脉注射通常用于对抗某些病毒感染的药物来杀死单个关节内的这些异常细胞，而无需使用手术。通过将一种通常由疱疹病毒产生的蛋白质基因注射到膝关节中，它将被排列在关节腔内的异常细胞所吸收，我们希望使这些细胞对一种名为更昔洛韦的药物变得脆弱，这种药物将通过静脉注射。先前的研究表明，通过手术切除滑膜关节衬里，或通过使用化学物质或放射疗法损伤滑膜关节，通常会导致该关节内关节炎的长期改善。我们希望以一种更有选择性的方式完成同样的事情。这种基因和抗病毒药物的结合只会导致滑膜内膜细胞的死亡，许多研究人员认为，这可能会导致用这种方法治疗的关节关节炎的长期缓解。

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.