Gene Therapy of Rheumatoid Arthritis

类风湿关节炎的基因治疗

• 批准号: 08557037
• 负责人: KOHSAKA Hitoshi
• 金额: $ 7.49万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557037/
• 关键词: Rheumatoid Arthritis; CDKI; Gene Therapy; p16; Adenovirus; p21; アデノウィルス

The synovia affected by rheumatoid arthritis (RA) is characterized by synovial proliferation which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed largely at correction of the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction. We studied the expression of cyclin dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. The results showed that the synoviial cells derived from hypertrophic synovia readily express pl6TNK4A when they were growth-inhibited. This was not. observed in other types of fibroblasts. In vivo adenoviral gene therapy with the plGINK4A gene efficiently inhibited the pathology in an animal model of RA.These observations indicated that the induction of pl6TNK4A may provide a novel approach to the effective treatment of RA.

受类风湿性关节炎（RA）影响的滑膜的特点是滑膜增殖，导致不可逆的软骨和骨质破坏。当前和实验性治疗主要旨在纠正潜在的免疫异常，但这些治疗通常证明在防止侵入性破坏方面无效。我们研究了类风湿滑膜细胞中细胞周期蛋白依赖性激酶抑制剂的表达，作为抑制滑膜细胞增殖的手段。结果显示，源自肥大滑膜的滑膜细胞在生长受到抑制时容易表达p16TNK4A。这不是。在其他类型的成纤维细胞中也观察到。使用plGINK4A基因的体内腺病毒基因治疗有效地抑制了RA动物模型中的病理学。这些观察结果表明p16TNK4A的诱导可能为有效治疗RA提供新的方法。

项目成果

上阪 等: "慢性関節リウマチの遺伝子治療" BioClinica. 発表予定.

Uesaka 等人：“类风湿性关节炎的基因治疗”BioClinica 预定演示。

上阪 等: "慢性関節リウマチの遺伝子治療" BioClinica. (発表予定).

Uesaka 等人：“类风湿性关节炎的基因治疗”BioClinica（待提交）。

上阪 等: "慢性関節リウマチの遺伝子治療" 骨・関節・靱帯. 第11巻10号. 1274-1275 (1998)

Uesaka 等人：“类风湿性关节炎的基因治疗”《骨骼、关节和韧带》，第 11 卷，第 10 期。1274-1275 (1998)

Hitoshi Kohsaka: "Gene Therapy of Rheumatoid Arthritis" Bone, Joint, and Ligament. 11-10. 1274-1275 (1999)

Hitoshi Kohsaka：“类风湿性关节炎的基因疗法”骨骼、关节和韧带。

Hitoshi Kohsaka: "Gene Therapy of Rheumatoid Arthritis" BioClinica. (in press).

Hitoshi Kohsaka：“类风湿性关节炎的基因疗法”BioClinica。