1998 Fiscal Year Final Research Report Summary

Gene Therapy of Rheumatoid Arthritis

Research Project

Project/Area Number	08557037
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	展開研究
Research Field	内科学一般
Research Institution	Tokyo Medical and Dental University
Principal Investigator	KOHSAKA Hitoshi First Department of Intemal Medicine, School of Medicine, Tokyo Medical and Dental University, Assistant, 医学部, 助手 (00251554)
Co-Investigator(Kenkyū-buntansha)	MIYASAKA Nobuyuki First Department of Intemal Medicine, School of Medicine, Tokyo Medical and Dent, 医学部, 教授 (30157622) SASANO Minoru Research and Development Santen Pharmaceuticals, 開発研究本部, 主任研究員 TERADA Yoshio Second Department of Intemal Medicine, School of Medicine , Tokyo Medical and De, 医学部, 助手 (30251531)
Project Period (FY)	1996 – 1998
Keywords	Rheumatoid Arthritis / CDKI / Gene Therapy / p16 / Adenovirus
Research Abstract	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.