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

通过体内基因转移进行分子滑囊切除术：第一阶段试验

• 批准号: 7376487
• 负责人: BLAKE J ROESSLER
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376487
• 关键词: genes; joints; orthopedics

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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们的医生和科学家小组正在研究一种新的实验方法，以减少类风湿性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。这些细胞生长到关节内并破坏关节内的软骨和骨骼。这些细胞也与风湿性关节炎患者关节内存在的炎症有关。通常，当这些细胞和发炎的组织无法用药物治疗时，可以通过手术切除这些组织。虽然这种类型的手术不能在特定的关节内治愈疾病，但它可能会在几个月甚至几年内提供改善。我们的程序旨在通过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相结合的方式，在单个关节内杀死这些异常细胞，而不需要手术。通过将一种通常由疱疹病毒制造的蛋白质的基因注入膝关节，在那里它将被排列在关节腔内的异常细胞摄取，我们希望让这些细胞对一种名为更昔洛韦的药物敏感，这种药物将被静脉注射。以前的研究表明，通过手术移除滑膜衬里，或者通过使用化学物质或放射治疗来损伤滑膜，通常会导致关节内关节炎的长期改善。我们希望以更有选择性的方式完成同样的事情。基因和抗病毒药物的结合应该只会导致滑膜衬里细胞的死亡，许多研究人员认为，这可能会导致使用这种方法治疗的关节的关节炎长期缓解。