| セッション情報 |
The 8th JSGE-AGA Joint Meeting
|
| タイトル |
JM-5：Treatment of Liver Fibrosis Using siRNA against a Collagen-specific Chaperone, Encapsulated in Vitamin A Coupled Liposomes
|
| 演者 |
Niitsu Yoshiro（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, Japan） |
| 共同演者 |
Yoneda Akinori（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, Japan）, Birukawa Naoko（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, Japan）, Kajiwara Keiko（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, JapanDELIMITEROn leave from Nitto Denko Corporation, Japan）, Miyazaki Miyono（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, JapanDELIMITEROn leave from Nitto Denko Corporation, Japan）, Sato Yosushi（4th Department of Internal Medicine, Sapporo Medical University, Japan）, Murase Kazuyuki（4th Department of Internal Medicine, Sapporo Medical University, Japan）, Tanaka Yasunobu（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, JapanDELIMITEROn leave from Nitto Denko Corporation, Japan）, Minomi Kenjirou（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, JapanDELIMITEROn leave from Nitto Denko Corporation, Japan）, Nishita Hiroki（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, Japan）, Fujita Ryosuke（Department of Molecular Target Exploration School of Medicine Sapporo Medical University, Japan） |
| 抄録 |
Despite the recent introduction of various antiviral agents, treatment of cirrhosis due to viral hepatitis is still an unmet medical need. Further, cirrhosis resulted from non-alcoholic steatohepatitis（NASH）of which incidence is dramatically increasing in western countries as well as Asia and etiology is not yet clarified, is also a target of drug development. Past several years, we have developed an antifibrosis modality, employing siRNA against collagen specific-chaperone, HSP47 encapsulated in VitaminA-coupled liposome. Using a prototype of this drug, we demonstrated a successful resolution of liver fibrosis in DMN rats, CCl4 rats and bile duct ligated rats. We also demonstrated validity of this approach for other organ fibroses involving in pancreas, lung etc. In addition, we disclosed the fact that during the treatment process of cirrhotic rats, regeneration of the liver occured even under continous administration of hepatotoxin. When we examined hepatic progenitor cells（EPCAM positive cells）in the cirrhotic tissue prior to the treatment, massive proliferation was observed in the area where collagen producing cells, activated hepatic stellate cells（aHSCs）were also proliferated. Upon regeneration after treatment, both progenitor cells and aHSCs disappeared. The disappearance was surmised to be due to the diminution of survival sustenance for aHSCs；MT1-MMP cleaved self collagen, and to the differentiation of progenitors into hepatocytes and cholangiocytes. When we cocultivated both cells, colonies consisted of inner progenitors and outer aHSCs was observed, suggesting niche formation. On the basis of these observations, we extended our drug development into clinical trial. The drug formulation for clinical use was totally distinct from that of prototype. As of end of November 2012, we have finished all required toxicology studies and are planning phase I study early next year in US. Details of this clinical plan will be reported at the meeting. |
| 索引用語 |
|
