Caspase inhibitors for the treatment of hepatitis C.
Decreasing hepatocyte injury and death is an attractive therapeutic target in chronic hepatitis C and other liver diseases. Apoptotic cell death is a critical mechanism responsible for liver injury in hepatitis C, and contributes to hepatic fibrogenesis. At the cellular level, apoptosis is executed by a family of cysteine proteases termed caspases. Caspase inhibitors have been developed to inhibit these proteases and attenuate cellular apoptosis in vivo. By reducing hepatocyte apoptosis these agents have the potential to serve as hepatoprotective agents, minimizing liver injury and fibrosis. Studies on a variety of animal models, and time-limited studies in human patients with hepatitis C suggest these are promising therapeutic agents. However, although these agents hold promise, their usefulness requires further studies, especially longer duration studies using hepatic fibrogenesis as the end point before they can be considered further for the treatment of patients infected with the hepatitis C virus.
Masuoka
Howard C
HC
Division of Gastroenterology and Hepatology, Miles and Shirley Fiterman Center for Digestive Diseases, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Guicciardi
Maria Eugenia
ME
Gores
Gregory J
GJ
D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology
D000590:Amino Acid Chloromethyl Ketones; D000998:Antiviral Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone